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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">ywfdn5LTfQwCTdPQdssCL3d</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2015002200265</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2015005050076</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20150076</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Reverse Auction: A Potential Strategy for Reduction of Pharmacological Therapy Cost</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Brand&#227;o</surname>
            <given-names>Sara Michelly Gon&#231;alves</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Issa</surname>
            <given-names>Victor Sarli</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ayub-Ferreira</surname>
            <given-names>Silvia Moreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Storer</surname>
            <given-names>Samantha</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gon&#231;alves</surname>
            <given-names>Bianca Gigliotti</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Valter Garcia</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carvas</surname>
            <given-names>Nelson</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Guilherme Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bocchi</surname>
            <given-names>Edimar Alcides</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <addr-line>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, SP - Brazil</institution>
        <institution content-type="normalized">Universidade de S&#227;o Paulo</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Mailing Address: Sara Michelly Gon&#231;alves Brand&#227;o</bold>, Av. Brigadeiro Lu&#237;s Ant&#244;nio, 1195 Ap 22, Bela Vista. Postal Code: 01317001, S&#227;o Paulo, SP &#8211; Brazil. E-mail: <email>saramichelly_brandao@yahoo.com.br</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Brand&#227;o SMG, Bocchi EA. Acquisition of data: Brand&#227;o SMG, Storer S, Gon&#231;alves BG, Santos VG. Analysis and interpretation of the data: Brand&#227;o SMG. Statistical analysis: Brand&#227;o SMG, Carvas Junior N. Writing of the manuscript: Brand&#227;o SMG, Bocchi EA. Critical revision of the manuscript for intellectual content: Brand&#227;o SMG, Issa VS, Ayub-Ferreira SM, Guimar&#227;es GV, Bocchi EA.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>21</day>
        <month>07</month>
        <year>2015</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>09</month>
        <year>2015</year>
      </pub-date>
      <volume>105</volume>
      <issue>3</issue>
      <fpage>265</fpage>
      <lpage>275</lpage>
      <history>
        <date date-type="received">
          <day>23</day>
          <month>01</month>
          <year>2015</year>
        </date>
        <date date-type="rev-recd">
          <day>04</day>
          <month>03</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>06</day>
          <month>04</month>
          <year>2015</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution NonCommercial License which permits unrestricted noncommercial use, distribution, and reproduction in any medium provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <sec>
          <title>Background:</title>
          <p>Polypharmacy is a significant economic burden.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>We tested whether using reverse auction (RA) as compared with commercial pharmacy (CP) to purchase medicine results in lower pharmaceutical costs for heart failure (HF) and heart transplantation (HT) outpatients.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>We compared the costs via RA versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and evaluated the influence of clinical and demographic variables on cost.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51-40.22) versus $161.76 (IQ 86.05&#8209;340.15) via CP; for HT, those costs were $393.08 (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>RA may reduce the cost of prescription drugs for HF and HT, potentially making HF treatment more accessible. Clinical characteristics can influence the cost and benefits of RA. RA may be a new health policy strategy to reduce costs of prescribed medications for HF and HT patients, reducing the economic burden of treatment.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart Failure</kwd>
        <kwd>Pharmaceutical Preparations / economics</kwd>
        <kwd>Competitive Bidding / economics</kwd>
        <kwd>Budgets</kwd>
        <kwd>Cost Savings</kwd>
        <kwd>Heart Transplantation</kwd>
      </kwd-group>
      <counts>
        <fig-count count="4"/>
        <table-count count="8"/>
        <equation-count count="0"/>
        <ref-count count="16"/>
        <page-count count="0"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>It is estimated that there are 5.1 million patients with heart failure (HF) in the United States of America (USA)<xref ref-type="bibr" rid="B01">1</xref> and 6.4 million patients in Brazil<xref ref-type="bibr" rid="B02">2</xref>. Heart failure was the single most frequent cause of hospitalization in the elderly population in Brazil<xref ref-type="bibr" rid="B02">2</xref>. Pharmacological therapy-oriented guidelines reduce progression, morbidity, mortality, and hospitalization in HF<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref>. Public and private spending on pharmaceuticals account for a substantial fraction of the total expenses of health care in developed and developing countries<xref ref-type="bibr" rid="B05">5</xref>. Heart failure is a cardiovascular disease with estimated costs of $32.4 billion in the USA in 2015<xref ref-type="bibr" rid="B06">6</xref>. Approximately 3% of the total cost of HF was expended on medications costing approximately $1.11 billion in 2009<xref ref-type="bibr" rid="B07">7</xref>. Surprisingly, despite the impact on HF costs, few studies have examined the pharmacological costs in patients with HF and the influence of demographic and clinical characteristics<xref ref-type="bibr" rid="B08">8</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref>. In addition, those few studies do not reflect contemporary practice. No previous study examined the influence of additional procedures, such as heart transplantation (HT).</p>
      <p>Health resources are scarce, but the needs are unlimited. Remarkably, strategies for reducing the cost of pharmacological HF treatments have not been tested, despite the impact of drug costs on government budgets and noncompliance with the use of medications. Studies regarding pharmacological treatments and their costs can provide a rationale for government policies to plan financial resources, and are essential tools for pharmacoeconomics in public health. Therefore, the purpose of this study was to compare the costs of the pharmacological treatment of HF and HT via reverse auction (RA)   <italic>versus</italic> estimated costs in commercial pharmacies (CP).</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Study population</title>
        <p>We retrospectively obtained the clinical, demographic, and pharmacological treatment data of all patients diagnosed with HF or of HT recipients consecutively managed at the Heart Failure Outpatient Clinic of Heart Institute of the Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo in Brazil. Demographic data collected included ethnicity escribed according to a previous study<xref ref-type="bibr" rid="B13">13</xref>, age, sex, comorbid condition, cause of HF, left ventricular ejection fraction (LVEF), number of ambulatory visits, medications, and most frequent stage of HF during the study period. The LVEF was obtained by use of any method, such as echocardiography, radionuclide ventriculography, cardiac magnetic resonance, or ventriculography via cardiac catheterization. The first LVEF of each patient in the study period was considered. The patients were being cared for by physicians and by a multidisciplinary team specialized in HF and HT from January 2009 through April 2011. Patients older than 16 years and on ambulatory care were included, except for one 9-year-old HT patient. Patients with incomplete clinical or cost information and any prescription drugs received during hospitalization were excluded.</p>
      </sec>
      <sec>
        <title>Study design</title>
        <p>Data relating to outpatient visits are stored in electronic health records so that any electronic medical prescription is automatically generated through an automated data-entry process. Medications are delivered every month to patients according to the last validated medical prescription. We retrieved information about all the medications each patient received, and the investigators reviewed all the medication information to ensure consistency.</p>
        <p>At our institution, which is a public body, drugs are purchased via RA. Reverse auction, is a mechanism through which, once consolidated the demand of the participating entities and established the technical characteristics of the products to be purchased, those with the best price are selected through electronic biddings towards the lowest. This guarantees a fair and transparent competition, and the most inexpensive prices of the market, especially in Latin American countries, such as Brazil. Purchases are financed by an annual budget assigned to each public body by public health funds. In procurement auctions for pharmaceuticals, suppliers bid for a very detailed contract of medicine supply, which specifies the drug, quantity, place and time schedule to delivery<xref ref-type="bibr" rid="B14">14</xref>.</p>
        <p>A procurement contract specifies a very detailed drug to be supplied, which is a unique combination of active ingredient, form, concentration, number of units, and packing. Public bodies are forbidden to procure a drug of a specific brand. They are obliged to acquire the drug from the lowest bid's supplier, which, in principle, can be a generic or a branded drug<xref ref-type="bibr" rid="B14">14</xref>.</p>
        <p>The medications are delivered gratuitously to patients treated at a public hospital according to the prescription. We compared the pharmacological treatment of HF and HT purchased via RA <italic>versus</italic> estimated costs in the private market in CP. The price of CP was defined using Bras&#237;ndice Pharmaceutical Guide, an official federal index that regulates drug marketing in Brazil (private cost): the Brazilian government sets maximum retail prices practiced by the pharmacies. The cost of each pill was based on the last institutional purchase in 2011 to avoid differences in prices between time periods. Value cost was converted into American dollars according to the market exchange rate of $0.50815 on April 12, 2013, to establish the values in a stable currency. The monthly cost per patient was calculated.</p>
        <p>Drugs included were beta-blockers, diuretics, calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), other cardiovascular drugs (OCD), lipid-lowering drugs, antiplatelet drugs, antiarrhythmic drugs, nitrates, anticoagulants or inhibitors of platelet adenosine diphosphate receptor (ACG-IPADPR), digitalis, immunosuppressants and other noncardiovascular drugs (ONCD). Drugs typically used for short course treatments (antibiotics) or on an as-needed basis (analgesics or sublingual nitroglycerin) were also included.</p>
        <p>We further analyzed costs according to clinical and demographic variables. The study protocol was approved by the Ethics Committee of the Instituto do Cora&#231;&#227;o de S&#227;o Paulo (registration number 22831813.2.0000.00680), which waived the need for patient consent because no identifying participant information was obtained.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>Measurement data are reported as mean &#177; standard deviation (SD) for variables normally distributed, and as medians within the interquartile range (IQ) for variables not normally distributed or as frequencies with percentages for all categorical variables. Univariate analysis was done with the chi-square or Fisher exact test to compare categorical variables. Normally distributed continuous variables were compared using the Student <italic>t</italic> test, and, for those non normally distributed, the Kruskal-Wallis test was used to assess differences between variables. Significant results demonstrated by the Kruskal-Wallis test were further analyzed for significance with the least significant difference (LSD) multiple-comparison <italic>post hoc</italic> test. To determine the correlation between continuous variables, we applied the correlation test according to normality distribution (<italic>r</italic>). The LVEF was analyzed in cohorts stratified into &#8804; 40% and &gt; 40%.</p>
        <p>The monthly cost per patient was log transformed. Multivariate analysis was performed with Generalized Estimating Equations (GEE), and the results expressed as nonstandardized coefficients (&#946;). Generalized Estimating Equations were applied using the continuous variables (age, LVEF, and ambulatory appointments), and the categorical variable 'cause of HF' as fixed effects. Comorbidities, functional class, ethnicity and sex were used as random effects. The advantage of this approach is that it used all available data and adjusted results based on correlations between outcomes and predictor variables. We used the criterion Wald chi-square test for choosing the best structure to be adopted in the model concerned. The quasi likelihood ratio test was also used to compare adjusted models.</p>
        <p>Statistical analysis was performed with SPSS 17.0. p-values &lt; 0.05 were considered significant, and p-values &lt; 0.10, as a trend.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Baseline characteristics (<xref ref-type="table" rid="t01">Table 1</xref>)</title>
        <table-wrap id="t01">
          <label>Table 1</label>
          <caption>
            <title> Baseline characteristics of the study population</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th align="left">
                  <bold>CHARACTERISTICS</bold>
                </th>
                <th align="center">
                  <bold>HF n = 808 n (%)</bold>
                </th>
                <th align="center">
                  <bold>HT n = 147 n (%)</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">
                  <bold>Age, years</bold>
                </td>
                <td align="center">56.5 &#177; 12.2</td>
                <td align="center">49.9 &#177; 16.6</td>
              </tr>
              <tr>
                <td align="left">&lt; 20</td>
                <td align="center">5(0.6)</td>
                <td align="center">9(6.1)</td>
              </tr>
              <tr>
                <td align="left">20 to 40</td>
                <td align="center">80 (9.9)</td>
                <td align="center">37 (25.2)</td>
              </tr>
              <tr>
                <td align="left">41 to 65</td>
                <td align="center">427 (52.8)</td>
                <td align="center">57 (11.8)</td>
              </tr>
              <tr>
                <td align="left">&#8805; 66</td>
                <td align="center">296 (36.6)</td>
                <td align="center">44 (29.9)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Ambulatory appointment</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">&lt; 5</td>
                <td align="center">250 (30.9)</td>
                <td align="center">16 (10.9)</td>
              </tr>
              <tr>
                <td align="left">6 to 10</td>
                <td align="center">302 (37.4)</td>
                <td align="center">17 (11.6)</td>
              </tr>
              <tr>
                <td align="left">11 to 15</td>
                <td align="center">127 (15.7)</td>
                <td align="center">42 (28.6)</td>
              </tr>
              <tr>
                <td align="left">16 to 20</td>
                <td align="center">48 (5.9)</td>
                <td align="center">28 (19.0)</td>
              </tr>
              <tr>
                <td align="left">&#8805; 21</td>
                <td align="center">81 (10.0)</td>
                <td align="center">44 (29.9)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Ethnicity</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">White and yellow</td>
                <td align="center">619 (78.3)</td>
                <td align="center">127 (86.4)</td>
              </tr>
              <tr>
                <td align="left">Black and mulatto</td>
                <td align="center">172 (21.7)</td>
                <td align="center">20 (13.6)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Cause</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Ischemic</td>
                <td align="center">141 (30.7)</td>
                <td align="center">18 (12.9)</td>
              </tr>
              <tr>
                <td align="left">Other causes</td>
                <td align="center">232 (50.5)</td>
                <td align="center">73 (52.5)</td>
              </tr>
              <tr>
                <td align="left">Chagasic</td>
                <td align="center">86 (18.7)</td>
                <td align="center">48 (34.5)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Sex</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Male</td>
                <td align="center">508 (62.9)</td>
                <td align="center">101 (68.7)</td>
              </tr>
              <tr>
                <td align="left">Female</td>
                <td align="center">300 (37.1)</td>
                <td align="center">46 (31.3)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Comorbidities</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Hypertension</td>
                <td align="center">157 (19.5)</td>
                <td align="center">40 (27.2)</td>
              </tr>
              <tr>
                <td align="left">Diabetes</td>
                <td align="center">150 (18.6)</td>
                <td align="center">30 (20.4)</td>
              </tr>
              <tr>
                <td align="left">Cerebrovascular accident</td>
                <td align="center">31 (3.9)</td>
                <td align="center">5 (3.4)</td>
              </tr>
              <tr>
                <td align="left">Renal Failure</td>
                <td align="center">56 (7.0)</td>
                <td align="center">18 (12.2)</td>
              </tr>
              <tr>
                <td align="left">COPD</td>
                <td align="center">13 (1.6)</td>
                <td align="center">2 (1.4)</td>
              </tr>
              <tr>
                <td align="left">Myocardial revascularization</td>
                <td align="center">20 (2.5)</td>
                <td align="center">0 (0.0)</td>
              </tr>
              <tr>
                <td align="left">Coronary angioplasty</td>
                <td align="center">9 (1.1)</td>
                <td align="center">2 (1.4)</td>
              </tr>
              <tr>
                <td align="left">Myocardial infarction</td>
                <td align="center">56 (7.0)</td>
                <td align="center">4 (2.7)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Prescribed cardiovascular drug</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Beta-blocker</td>
                <td align="center">703 (87.1)</td>
                <td align="center">40 (27.2)</td>
              </tr>
              <tr>
                <td align="left">Diuretic</td>
                <td align="center">703 (87.1)</td>
                <td align="center">54 (36.7)</td>
              </tr>
              <tr>
                <td align="left">CCB</td>
                <td align="center">205 (25.4)</td>
                <td align="center">114 (77.6)</td>
              </tr>
              <tr>
                <td align="left">ACEI, ARB</td>
                <td align="center">573(71.0)</td>
                <td align="center">54 (36.7)</td>
              </tr>
              <tr>
                <td align="left">Lipid-lowering</td>
                <td align="center">595 (73.7)</td>
                <td align="center">117 (79.6)</td>
              </tr>
              <tr>
                <td align="left">Antiplatelet drug</td>
                <td align="center">354 (43.9)</td>
                <td align="center">30 (20.4)</td>
              </tr>
              <tr>
                <td align="left">ACG or IPADPR</td>
                <td align="center">212 (26.3)</td>
                <td align="center">20 (13.6)</td>
              </tr>
              <tr>
                <td align="left">Antiarrhythmic drug</td>
                <td align="center">85 (10.5)</td>
                <td align="center">4 (2.7)</td>
              </tr>
              <tr>
                <td align="left">Digitalis</td>
                <td align="center">309 (38.3)</td>
                <td align="center">15 (10.2)</td>
              </tr>
              <tr>
                <td align="left">Nitrate</td>
                <td align="center">197 (24.4)</td>
                <td align="center">11 (7.5)</td>
              </tr>
              <tr>
                <td align="left">OCD</td>
                <td align="center">330 (40.9)</td>
                <td align="center">47 (32.0)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Prescribed non-cardiovascular drug</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Antibiotic</td>
                <td align="center">42 (5.2)</td>
                <td align="center">68 (46.3)</td>
              </tr>
              <tr>
                <td align="left">Immunosuppressant</td>
                <td align="center">0 (0)</td>
                <td align="center">147 (100)</td>
              </tr>
              <tr>
                <td align="left">ONCD</td>
                <td align="center">630 (78.1)</td>
                <td align="center">147 (100)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>HF: heart failure; HT: heart transplantation; COPD: chronic obstructive pulmonary disease; ACG: anticoagulants; IPADPR: inhibitor of platelet adenosine <italic>diphosphate</italic> receptor; ONCD: other noncardiovascular drugs; beta-blockers (atenolol, bisoprolol, metoprolol, carvedilol, propranolol, sotalol); diuretics (furosemide, hydrochlorothiazide, chlorthalidone, spironolactone); CCB: calcium channel blockers (diltiazem, verapamil, amlodipine, nifedipine, losartan); ACEI: angiotensin-converting enzyme inhibitors (captopril, enalapril, lisinopril); ARB: angiotensin receptor blockers, lipid-lowering drugs (atorvastatin, ciprofibrate, ezetimibe, rosuvastatin, simvastatin); antiplatelet drugs (aspirin); ACG or IPADPR (enoxaparin, warfarin, clopidogrel); antiarrhythmic drug (amiodarone, propafenone); digitalis (digoxin); nitrates (isosorbide, propatylnitrate); OCD: other cardiovascular drugs (clonidine, doxazosin, hydralazine, methyldopa).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>In the HF group, the mean time of study follow-up was 16.7 &#177; 8.8 months, with a median number of eight ambulatory appointments for each patient, whereas, in the HT group, the study follow-up was 23.1 &#177; 5.8 months, and the median number of ambulatory appointments for each patient was 16. A total of 8,448 medical prescriptions were analyzed in HF patients, and 3,217 medical prescriptions in HT recipients. Complete cost data could not be retrieved in 82 (10.1%) patients with HF and in 1 (0.7%) HT recipient, and these patients were excluded. Ambulatory appointments were more frequent among HF patients in functional class III and IV as compared with those in class I and II. In patients with functional class III and IV, 26.8% of the cause was chagasic, 34.1% ischemic, and 39% other causes, compared with 12.9%, 29.6%, and 57.5%, respectively, in patients with functional class I and II (p = 0.003).</p>
      </sec>
      <sec>
        <title>Drugs prescribed for HF</title>
        <p>The most frequently prescribed drugs in descending order were beta-blockers, diuretics, ONCD, lipid-lowering drugs, ACEI-ARBs (<xref ref-type="table" rid="t01">Table 1</xref>). Prescribed drugs differed between patients with LVEF &#8804;40% and those with LVEF &gt; 40%. Beta-blockers, diuretics, antiplatelet drugs, antiarrhythmic drugs and nitrates were more frequently prescribed for HF patients with LVEF &#8804; 40%, whereas CCB prescriptions were more frequent for patients with LVEF &gt; 40% (<xref ref-type="table" rid="t02">Table 2</xref>). Beta-blockers (75.9%, p = 0.009), diuretics (75.9%, p = 0.009), ACEI-ARB (76.6%, p = 0.034), nitrate (61.9%, p = 0.001) and OCD (68.8%, p = 0.036) were more frequently prescribed in functional classes I and II. Patients of white and yellow ethnicity received more OCD (74.1%, p = 0.015) and antiplatelet drugs (82.2%, p = 0.018). Calcium channel blockers (60.3%, p &lt; 0.001) and lipid-lowering drugs (47%, p &lt; 0.001) were more frequently prescribed for other causes, while antiplatelet drugs (53.3%, p &lt; 0.001) and nitrates (43%, p &lt; 0.001) were more frequently prescribed for ischemic patients, and antiarrhythmic drugs (41%, p &lt; 0.001) for chagasic patients. ACEI-ARB (33.3%, p = 0.001), OCD (42.1%, p = 0.013), antiplatelet drugs (31.4%, p = 0.003) and ONCD (40.2%, p = 0.001) were less frequently prescribed for female patients.</p>
        <table-wrap id="t02">
          <label>Table 2</label>
          <caption>
            <title> Profile of prescribed drugs according to left ventricular ejection fraction</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th rowspan="2" align="left">
                  <bold>Prescribed drug</bold>
                </th>
                <th colspan="3" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>HF</bold>
                </th>
                <th colspan="3" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>HT</bold>
                </th>
              </tr>
              <tr>
                <th align="center">
                  <bold>LVEF &#8804; 40% (n = 321) n (%)</bold>
                </th>
                <th align="center">
                  <bold>LVEF &gt; 40% (n = 134) n (%)</bold>
                </th>
                <th align="center">
                  <bold>p</bold>
                </th>
                <th align="center">
                  <bold>LVEF &#8804; 40% (n = 10) n(%)</bold>
                </th>
                <th align="center">
                  <bold>LVEF &gt; 40% (n = 126) n (%)</bold>
                </th>
                <th align="center">
                  <bold>p</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Beta-blocker</td>
                <td align="center">287 (89.4)</td>
                <td align="center">109(81.3)</td>
                <td align="center">0.020</td>
                <td align="center">5(50.0)</td>
                <td align="center">32 (25.4)</td>
                <td align="center">0.13</td>
              </tr>
              <tr>
                <td align="left">Diuretic</td>
                <td align="center">287(89.4)</td>
                <td align="center">109(81.3)</td>
                <td align="center">0.020</td>
                <td align="center">4(40.0)</td>
                <td align="center">48(38.1)</td>
                <td align="center">1.00</td>
              </tr>
              <tr>
                <td align="left">CCB</td>
                <td align="center">67(20.9)</td>
                <td align="center">43(32.1)</td>
                <td align="center">0.011</td>
                <td align="center">7(70.0)</td>
                <td align="center">102(81.0)</td>
                <td align="center">0.41</td>
              </tr>
              <tr>
                <td align="left">ACEI, ARB</td>
                <td align="center">221(68.8)</td>
                <td align="center">90(67.2)</td>
                <td align="center">0.72</td>
                <td align="center">6(60.0)</td>
                <td align="center">46(36.5)</td>
                <td align="center">0.18</td>
              </tr>
              <tr>
                <td align="left">OCD</td>
                <td align="center">153(47.7)</td>
                <td align="center">55(41.0)</td>
                <td align="center">0.19</td>
                <td align="center">5(50.0)</td>
                <td align="center">41(32.5)</td>
                <td align="center">0.30</td>
              </tr>
              <tr>
                <td align="left">Lipid-lowering</td>
                <td align="center">241(75.1)</td>
                <td align="center">89(27.0)</td>
                <td align="center">0.059</td>
                <td align="center">7(70.0)</td>
                <td align="center">106(84.1)</td>
                <td align="center">0.37</td>
              </tr>
              <tr>
                <td align="left">Antiplatelet</td>
                <td align="center">154(48.0)</td>
                <td align="center">44(32.8)</td>
                <td align="center">0.003</td>
                <td align="center">3(30.0)</td>
                <td align="center">24(19.0)</td>
                <td align="center">0.41</td>
              </tr>
              <tr>
                <td align="left">ACG or IPADPR</td>
                <td align="center">93(29.0)</td>
                <td align="center">39(29.1)</td>
                <td align="center">0.97</td>
                <td align="center">1(10.0)</td>
                <td align="center">19(15.1)</td>
                <td align="center">1.00</td>
              </tr>
              <tr>
                <td align="left">Antiarrhythmic</td>
                <td align="center">44(13.7)</td>
                <td align="center">9(6.7)</td>
                <td align="center">0.034</td>
                <td align="center">0(0.0)</td>
                <td align="center">3(100)</td>
                <td align="center">NP</td>
              </tr>
              <tr>
                <td align="left">Digitalis</td>
                <td align="center">127(39.6)</td>
                <td align="center">44(32.8)</td>
                <td align="center">0.17</td>
                <td align="center">0(0.0)</td>
                <td align="center">15(11.9)</td>
                <td align="center">NP</td>
              </tr>
              <tr>
                <td align="left">Nitrate</td>
                <td align="center">104(32.4)</td>
                <td align="center">24(17.9)</td>
                <td align="center">0.002</td>
                <td align="center">3(30.0)</td>
                <td align="center">7(5.6)</td>
                <td align="center">0.026</td>
              </tr>
              <tr>
                <td align="left">Antibiotic</td>
                <td align="center">25(7.8)</td>
                <td align="center">7(5.2)</td>
                <td align="center">0.33</td>
                <td align="center">5(50.0)</td>
                <td align="center">62(49.2)</td>
                <td align="center">1.00</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>HF: heart failure; HT: heart transplantation; EF: ejection fraction; NP: not possible; ACG: anticoagulants; IPADPR: inhibitors of platelet adenosine diphosphate receptor; beta-blockers (atenolol, bisoprolol, metoprolol, carvedilol, propranolol, sotalol); diuretics (furosemide, hydrochlorothiazide, chlorthalidone, spironolactone); CCB: calcium channel blockers (diltiazem, verapamil, amlodipine, nifedipine, losartan); ACEI: angiotensin-converting enzyme inhibitors (captopril, enalapril, lisinopril); ARB: angiotensin receptor blockers; OCD: other cardiovascular drugs (clonidine, doxazosin, hydralazine, methyldopa); lipid-lowering drugs (atorvastatin, ciprofibrate, ezetimibe, rosuvastatin, simvastatin); antiplatelet drug (aspirin), ACG or IPADPR (enoxaparin, warfarin, clopidogrel); antiarrhythmic drugs (amiodarone, propafenone), digitalis (digoxin); nitrates (isosorbide, propatylnitrate).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>In the HF group, men consumed lower doses of atenolol, captopril, losartan, spironolactone, and isosorbide, and higher doses of carvedilol and hydralazine, but equal doses of enalapril, although the difference was not statistically significant among daily prescribed medication doses between sexes. In respect to functional class, the median doses of enalapril in functional class III and IV and also I and II were 30.28 mg/daily (IQ 14.12-35.79) and 33.85 mg/daily (IQ 22.00-38.67), respectively (p = 0.014). The median doses of captopril were 39.58 mg/daily (IQ 13.54-107.29) and 77.52 mg/daily (IQ 43.23-146.42), respectively (p = 0.059). Regarding ethnicity, African-Brazilians (black and mulatto) used more enalapril (35.42 mg/daily, IQ 23.61-39.27) than white and yellow Brazilians (32.93 mg/daily, IQ 18.33-37.78) (p = 0.039). Concerning age, 41 to 65 year-old patients with HF more frequently received enalapril (34.29 mg/daily, IQ 20.21-38.65, p = 0.019) and spironolactone (25.93 mg/daily, IQ 24.24-30.56, p = 0.049), a trend toward higher doses of carvedilol (48.08 mg/daily, IQ 35.04-62.50, p = 0.076) and captopril (93.05 mg/daily, IQ 66.67-145.4, p = 0.087) being observed. Regarding cause, lower doses of carvedilol (42.11 mg/daily, IQ 25.00-50.00, p &lt; 0.001) and enalapril (23.33 mg/daily, IQ 14.44-32.22, p &lt; 0.001) were administered to chagasic patients as compared to ischemic patients and those with heart disease of other causes, and lower doses of losartan (85.55mg/daily, IQ 52.77-100.00, p = 0.021) were administered to chagasic and ischemic patients as compared to those with heart disease of other causes. The correlations between daily consumption of carvedilol and LVEF were weak (r =.125, p = 0.017).</p>
        <p>In the HT group, immunosuppressants, ONCD, lipid-lowering drugs and CCB were most frequently prescribed (<xref ref-type="table" rid="t01">Table 1</xref>). Additionally, there was a difference regarding the use of nitrates between patients with LVEF &#8804; 40% and those with LVEF &gt; 40% (p = 0.026) (<xref ref-type="table" rid="t02">Table 2</xref>). Patients of white and yellow ethnicity received more antibiotics (77.9%, p = 0.006). With respect to cause, differences were not statistically significant among the drugs used. Concerning sex, antibiotics were more frequently used by men than by women (58.8%, p = 0.016). <xref ref-type="fig" rid="f01">Figure 1</xref> shows the magnitude of cost reduction for drugs purchased via RA.</p>
        <fig id="f01">
          <label>Figure 1</label>
          <caption>
            <title>Percentage cost reduction in delivered prescription drugs purchased via reverse auction in comparison with private costs according to each drug group in heart failure (Top) and heart transplantation (Bottom). Immunosup: immunosuppressants; ONCD: other noncardiovascular drugs; CCB: calcium channel blockers; ACEI: angiotensin-converting enzyme inhibitors; ARB: angiotensin receptor blockers; OCD: other cardiovascular drugs; Antiplatelet: antiplatelet drugs; ACG: anticoagulants; IPADPR: inhibitors of platelet adenosine diphosphate receptor.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-105-03-0265-50076-gf01.jpg"/></fig>
      </sec>
      <sec>
        <title>Cost of pharmacological treatment via reverse auction</title>
        <p>In HF patients, the total cost was $534,010.20 (n = 726), and the median monthly cost per patient was $10.15 (IQ 3.51-40.22). The most costly classes of drugs in decreasing order of value were ONCD, lipid-lowering drugs and OCD (<xref ref-type="table" rid="t03">Table 3</xref>).</p>
        <table-wrap id="t03">
          <label>Table 3</label>
          <caption>
            <title>Total cost in dollars of prescribed drugs for heart failure and heart transplantation study populations</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th rowspan="3" align="left">
                  <bold>Prescribed drug</bold>
                </th>
                <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>HF</bold>
                </th>
                <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>HT</bold>
                </th>
              </tr>
              <tr>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Reverse Auction</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Reverse Auction</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Private</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Private</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Reverse Auction</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Reverse Auction</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Private</bold>
                </th>
                <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>Private</bold>
                </th>
              </tr>
              <tr>
                <th align="center">
                  <bold>Total</bold>
                </th>
                <th align="center">
                  <bold>%</bold>
                </th>
                <th align="center">
                  <bold>Total</bold>
                </th>
                <th align="center">
                  <bold>%</bold>
                </th>
                <th align="center">
                  <bold>Total</bold>
                </th>
                <th align="center">
                  <bold>%</bold>
                </th>
                <th align="center">
                  <bold>Total</bold>
                </th>
                <th align="center">
                  <bold>%</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Beta-blocker</td>
                <td align="center">5,587.37</td>
                <td align="center">1.05</td>
                <td align="center">594,268.42</td>
                <td align="center">14.89</td>
                <td align="center">600.39</td>
                <td align="center">0.03</td>
                <td align="center">13,832.19</td>
                <td align="center">0.24</td>
              </tr>
              <tr>
                <td align="left">Diuretic</td>
                <td align="center">7,656.28</td>
                <td align="center">1.43</td>
                <td align="center">146,626.03</td>
                <td align="center">3.67</td>
                <td align="center">368.85</td>
                <td align="center">0.02</td>
                <td align="center">8,441.09</td>
                <td align="center">0.15</td>
              </tr>
              <tr>
                <td align="left">CCB</td>
                <td align="center">1,212.11</td>
                <td align="center">0.23</td>
                <td align="center">58,448.57</td>
                <td align="center">1.46</td>
                <td align="center">6,847.05</td>
                <td align="center">0.38</td>
                <td align="center">51,373.17</td>
                <td align="center">0.90</td>
              </tr>
              <tr>
                <td align="left">ACEI, ARB</td>
                <td align="center">16,905.47</td>
                <td align="center">3.16</td>
                <td align="center">209,315.46</td>
                <td align="center">5.24</td>
                <td align="center">2,102.12</td>
                <td align="center">0.12</td>
                <td align="center">15,675.55</td>
                <td align="center">0.27</td>
              </tr>
              <tr>
                <td align="left">OCD</td>
                <td align="center">24,174.38</td>
                <td align="center">4.52</td>
                <td align="center">162,075.63</td>
                <td align="center">4.06</td>
                <td align="center">4,846.76</td>
                <td align="center">0.27</td>
                <td align="center">15,933.67</td>
                <td align="center">0.28</td>
              </tr>
              <tr>
                <td align="left">Lipid-lowering</td>
                <td align="center">79,108.02</td>
                <td align="center">14.80</td>
                <td align="center">196,806.89</td>
                <td align="center">4.93</td>
                <td align="center">6,267.88</td>
                <td align="center">0.35</td>
                <td align="center">66,905.15</td>
                <td align="center">1.17</td>
              </tr>
              <tr>
                <td align="left">Antiplatelet</td>
                <td align="center">566.45</td>
                <td align="center">0.11</td>
                <td align="center">19,825.63</td>
                <td align="center">0.50</td>
                <td align="center">67.07</td>
                <td align="center">0.00</td>
                <td align="center">2,347.49</td>
                <td align="center">0.04</td>
              </tr>
              <tr>
                <td align="left">ACG or IPADPR</td>
                <td align="center">7,911.35</td>
                <td align="center">0.15</td>
                <td align="center">58.458,19</td>
                <td align="center">1.46</td>
                <td align="center">662.50</td>
                <td align="center">0.04</td>
                <td align="center">9,667.25</td>
                <td align="center">0.17</td>
              </tr>
              <tr>
                <td align="left">Antiarrhythmic</td>
                <td align="center">1,993.28</td>
                <td align="center">0.37</td>
                <td align="center">17,018.91</td>
                <td align="center">0.43</td>
                <td align="center">40.55</td>
                <td align="center">0.00</td>
                <td align="center">729.86</td>
                <td align="center">0.01</td>
              </tr>
              <tr>
                <td align="left">Digitalis</td>
                <td align="center">672.34</td>
                <td align="center">0.13</td>
                <td align="center">15,980.01</td>
                <td align="center">0.40</td>
                <td align="center">18,70</td>
                <td align="center">0.00</td>
                <td align="center">336.58</td>
                <td align="center">0.01</td>
              </tr>
              <tr>
                <td align="left">Nitrate</td>
                <td align="center">5,300.55</td>
                <td align="center">0.99</td>
                <td align="center">37,563.87</td>
                <td align="center">0.94</td>
                <td align="center">559.03</td>
                <td align="center">0.03</td>
                <td align="center">1,799.95</td>
                <td align="center">0.03</td>
              </tr>
              <tr>
                <td align="left">Antibiotic</td>
                <td align="center">217.40</td>
                <td align="center">0.04</td>
                <td align="center">5,880.07</td>
                <td align="center">0.15</td>
                <td align="center">6,647.44</td>
                <td align="center">0.37</td>
                <td align="center">199,964.37</td>
                <td align="center">3.49</td>
              </tr>
              <tr>
                <td align="left">Immunosuppressant</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">-</td>
                <td align="center">1,540,724.53</td>
                <td align="center">86.20</td>
                <td align="center">4,159,017.41</td>
                <td align="center">72.63</td>
              </tr>
              <tr>
                <td align="left">ONCD</td>
                <td align="center">390,244.35</td>
                <td align="center">73.02</td>
                <td align="center">2,468,908.68</td>
                <td align="center">61.86</td>
                <td align="center">217,709.30</td>
                <td align="center">12.18</td>
                <td align="center">1,179,687.44</td>
                <td align="center">20.60</td>
              </tr>
              <tr>
                <td align="left">TOTAL</td>
                <td align="center">534,428.49</td>
                <td align="center">100</td>
                <td align="center">3,991,176.38</td>
                <td align="center">100</td>
                <td align="center">1,787,462.17</td>
                <td align="center">100</td>
                <td align="center">5,725,965.20</td>
                <td align="center">100</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>HF: heart failure; HT: heart transplantation; ACG: anticoagulants; IPADPR: inhibitors of platelet adenosine diphosphate receptor; ONCD: other noncardiovascular drugs; beta-blockers (atenolol, bisoprolol, metoprolol, carvedilol, propranolol, sotalol); diuretics (furosemide, hydrochlorothiazide, chlorthalidone, spironolactone); CCB: calcium channel blockers (diltiazem, verapamil, amlodipine, nifedipine, losartan); ACEI: angiotensin-converting enzyme inhibitors (captopril, enalapril, lisinopril); ARB: angiotensin receptor blockers; lipid-lowering drugs (atorvastatin, ciprofibrate, ezetimibe, rosuvastatin, simvastatin); antiplatelet drug (aspirin), ACG or IPADPR (enoxaparin, warfarin, clopidogrel); antiarrhythmic drugs (amiodarone, propafenone); digitalis (digoxin); nitrates (isosorbide, propatylnitrate); OCD: other cardiovascular drugs (clonidine, doxazosin, hydralazine, methyldopa).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>On the other hand, the total cost for HT recipients was $1,787,462.17 (n = 146), and the median monthly cost per patient was $393.08 (IQ 124.74-774.76). The most costly classes of drugs were immunosuppressants and ONCD (<xref ref-type="table" rid="t03">Table 3</xref>).</p>
      </sec>
      <sec>
        <title>Cost of pharmacological treatment via private market</title>
        <p>In HF patients, the estimated total cost was $3,991,176.38 (n = 726), and the median monthly cost per patient was $161.76 (IQ 86.05-340.15). The most costly classes of drugs in decreasing value were ONCD and beta-blockers (<xref ref-type="table" rid="t03">Table 3</xref>).</p>
        <p>For HT patients, the total cost was $5,725,965.20 (n = 146), and the median monthly cost per patient was $1,207.70 (IQ 604.48-2,499.97). Not surprisingly, the most costly classes of drugs were immunosuppressants and ONCD (<xref ref-type="table" rid="t03">Table 3</xref>).</p>
      </sec>
      <sec>
        <title>Cost via reverse auction according to subgroup analyses</title>
        <p>The monthly median cost per HF patient was $9.74 (IQ 3.48-33.65, n = 453) for men and $12.24 (IQ 3.57-44.01, n = 273) for women (p = 0.127). An increment in monthly median cost for HF was observed in hypertension (p &lt; 0.001) and diabetes (p &lt; 0.001). Hypertension was responsible for an incremental cost of $8.02 (48% higher) (p &lt; 0.001) and diabetes, for an incremental cost of $24.35 (76% higher) (p &lt; 0.001). The cost for ischemic cardiomyopathy ($16.84, IQ 6.32-16.84) was significantly higher than that for Chagas' disease ($8.53, IQ 2.98-26.52, p &lt; 0.001) and other causes ($6.79, IQ 3.21-18.58, p &lt; 0.001). The lower cost for Chagas' disease may be due to the fact that chagasic patients may not tolerated full doses and doctors are not encouraged to use full doses because there is no trial in Chagas' disease. In the multivariate analysis, older HF subjects had significantly higher costs (&#946; = .021, p &lt; 0.001), and patients without hypertension and diabetes had significantly lower costs (&#946; = -.517, p &lt; 0.001; &#946; = -.979, p &lt; 0.001). The magnitude of cost reduction via RA was higher in diabetes and hypertension (<xref ref-type="fig" rid="f02">Figure 2</xref>).</p>
        <fig id="f02">
          <label>Figure 2</label>
          <caption>
            <title>Cost of delivered prescription drugs purchased via reverse auction (RA) compared with commercial pharmacy (CP) costs according to the diagnosis of systemic arterial hypertension and diabetes mellitus in heart failure and heart transplantation.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-105-03-0265-50076-gf02.jpg"/></fig>
        <p>In the HT group, the monthly median cost per patient was $365.17 (IQ 100.83-683.59, n = 101) for men and $435.58 (IQ 248.40-920.86, n = 45) for women (p = 0.268). None of the comorbidities caused an incremental cost. Differences were statistically significant between the costs of patients with a previous history of chagasic cardiomyopathy ($271.71, IQ 66.49-568.54) and other causes ($472.40, IQ 182.05-888.53, p = 0.009). Additional parallels between clinical variables and monthly median cost for both groups are shown in <xref ref-type="table" rid="t04">Table 4</xref>. In multivariate analysis, HT patients without hypertension had lower cost (&#946; = -.324, p &lt; 0.001). In this model, other variables were not statistically significant in predicting cost. The magnitude of cost reduction via RA was higher in diabetes and hypertension (<xref ref-type="fig" rid="f02">Figure 2</xref>).</p>
        <table-wrap id="t04">
          <label>Table 4</label>
          <caption>
            <title>Monthly cost via reverse auction or commercial pharmacies of prescribed drugs for heart failure and heart transplantation study populations according to clinical and demographic variables</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th rowspan="2" align="left">
                  <bold>CHARACTERISTICS</bold>
                </th>
                <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>HF</bold>
                </th>
                <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                  <bold>HT</bold>
                </th>
              </tr>
              <tr>
                <th>
                  <bold>n</bold>
                </th>
                <th>
                  <bold>MEDIAN COST</bold>
                </th>
                <th>
                  <bold>IQ 25%-75%</bold>
                </th>
                <th>
                  <bold>p</bold>
                </th>
                <th>
                  <bold>n</bold>
                </th>
                <th>
                  <bold>MEDIAN COST</bold>
                </th>
                <th>
                  <bold>IQ 25%-75%</bold>
                </th>
                <th>
                  <bold>p</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">
                  <bold>Reverse auction cost in $</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Age, y</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&lt; 0.001</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.19</td>
              </tr>
              <tr>
                <td align="left">&#8804; 19</td>
                <td align="center">5</td>
                <td align="center">3.16</td>
                <td align="center">2.87-24.39</td>
                <td align="center">&#160;</td>
                <td align="center">9</td>
                <td align="center">732.48</td>
                <td align="center">493.62-1,026.12</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">20 to 40</td>
                <td align="center">68</td>
                <td align="center">4.35</td>
                <td align="center">2.07-15.63</td>
                <td align="center">&#160;</td>
                <td align="center">37</td>
                <td align="center">410.07</td>
                <td align="center">239.07-844.68</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">41 to 65</td>
                <td align="center">380</td>
                <td align="center">9.8</td>
                <td align="center">3.20-45.88</td>
                <td align="center">&#160;</td>
                <td align="center">57</td>
                <td align="center">365.19</td>
                <td align="center">97.16-619.52</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">&#8805; 65</td>
                <td align="center">273</td>
                <td align="center">13.46</td>
                <td align="center">4.80-52.75</td>
                <td align="center">&#160;</td>
                <td align="center">43</td>
                <td align="center">245.93</td>
                <td align="center">90.60-1,021.26</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Causes</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&lt; 0.001</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.036</td>
              </tr>
              <tr>
                <td align="left">Ischemic</td>
                <td align="center">132</td>
                <td align="center">16.84</td>
                <td align="center">6.32-16.84</td>
                <td align="center">&#160;</td>
                <td align="center">18</td>
                <td align="center">402.49</td>
                <td align="center">77.07-932.54</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Chagasic</td>
                <td align="center">76</td>
                <td align="center">8.53</td>
                <td align="center">2.98-26.52</td>
                <td align="center">&#160;</td>
                <td align="center">48</td>
                <td align="center">271.71</td>
                <td align="center">66.49-568.54</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Others</td>
                <td align="center">217</td>
                <td align="center">6.79</td>
                <td align="center">3.21-18.58</td>
                <td align="center">&#160;</td>
                <td align="center">73</td>
                <td align="center">472.40</td>
                <td align="center">182.05-888.53</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Ambulatory appointment, times</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.005</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.016</td>
              </tr>
              <tr>
                <td align="left">&lt; 5</td>
                <td align="center">192</td>
                <td align="center">10.84</td>
                <td align="center">2.88-39,19</td>
                <td align="center">&#160;</td>
                <td align="center">16</td>
                <td align="center">576.34</td>
                <td align="center">292.84-1,396.98</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">6 to 10</td>
                <td align="center">286</td>
                <td align="center">8.09</td>
                <td align="center">3.07-30.27</td>
                <td align="center">&#160;</td>
                <td align="center">16</td>
                <td align="center">512.22</td>
                <td align="center">149.78-1,062.56</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">11 to 15</td>
                <td align="center">124</td>
                <td align="center">15.13</td>
                <td align="center">5.23-70.22</td>
                <td align="center">&#160;</td>
                <td align="center">42</td>
                <td align="center">227.05</td>
                <td align="center">73.86-607.01</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">16 to 20</td>
                <td align="center">46</td>
                <td align="center">6.55</td>
                <td align="center">2.91-54.35</td>
                <td align="center">&#160;</td>
                <td align="center">28</td>
                <td align="center">273.05</td>
                <td align="center">61.67-654.69</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">&#8805; 21</td>
                <td align="center">78</td>
                <td align="center">12.89</td>
                <td align="center">5.06-41.86</td>
                <td align="center">&#160;</td>
                <td align="center">44</td>
                <td align="center">493.46</td>
                <td align="center">223.14-847.01</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Functional class</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&lt; 0.001</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">I and II</td>
                <td align="center">326</td>
                <td align="center">7.04</td>
                <td align="center">2.82-32.86</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">III and IV</td>
                <td align="center">101</td>
                <td align="center">16.47</td>
                <td align="center">5.43-67.55</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Ethnicity</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.96</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.34</td>
              </tr>
              <tr>
                <td align="left">White and yellow</td>
                <td align="center">564</td>
                <td align="center">10.07</td>
                <td align="center">3.59-10.07</td>
                <td align="center">&#160;</td>
                <td align="center">126</td>
                <td align="center">390.47</td>
                <td align="center">118.43-737.32</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Black and mulatto</td>
                <td align="center">148</td>
                <td align="center">10.92</td>
                <td align="center">3.52-40.47</td>
                <td align="center">&#160;</td>
                <td align="center">20</td>
                <td align="center">40.47</td>
                <td align="center">225.65-1,074.95</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>LVEF</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.43</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.97</td>
              </tr>
              <tr>
                <td align="left">&#8804; 40%</td>
                <td align="center">296</td>
                <td align="center">11.82</td>
                <td align="center">3.47-47.80</td>
                <td align="center">&#160;</td>
                <td align="center">10</td>
                <td align="center">358.93</td>
                <td align="center">86.11-957.32</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">&gt; 40%</td>
                <td align="center">119</td>
                <td align="center">9.46</td>
                <td align="center">3.72-27.61</td>
                <td align="center">&#160;</td>
                <td align="center">126</td>
                <td align="center">390.47</td>
                <td align="center">124.75-740.92</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Private cost in $</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Age, y</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&lt; 0.001</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.52</td>
              </tr>
              <tr>
                <td align="left">&#8804; 19</td>
                <td align="center">5</td>
                <td align="center">105.45</td>
                <td align="center">52.69-520.48</td>
                <td align="center">&#160;</td>
                <td align="center">09</td>
                <td align="center">1,851.58</td>
                <td align="center">1,284.76-2,755.11</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">20 to 40</td>
                <td align="center">68</td>
                <td align="center">114.52</td>
                <td align="center">62.57-188.12</td>
                <td align="center">&#160;</td>
                <td align="center">37</td>
                <td align="center">1,234.25</td>
                <td align="center">839.74-2,455.04</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">41 to 65</td>
                <td align="center">380</td>
                <td align="center">148.90</td>
                <td align="center">79.68-331.97</td>
                <td align="center">&#160;</td>
                <td align="center">57</td>
                <td align="center">1,155.17</td>
                <td align="center">556.26-2,491.22</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">&#8805; 65</td>
                <td align="center">273</td>
                <td align="center">193.19</td>
                <td align="center">113.57-420.72</td>
                <td align="center">&#160;</td>
                <td align="center">43</td>
                <td align="center">1,004.99</td>
                <td align="center">572.62-2,734.57</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Causes</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.004</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.14</td>
              </tr>
              <tr>
                <td align="left">Ischemic</td>
                <td align="center">132</td>
                <td align="center">200.96</td>
                <td align="center">113.73-447.87</td>
                <td align="center">&#160;</td>
                <td align="center">18</td>
                <td align="center">1,581.77</td>
                <td align="center">554.10-3,141.53</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Chagasic</td>
                <td align="center">76</td>
                <td align="center">138.85</td>
                <td align="center">19.03-303.53</td>
                <td align="center">&#160;</td>
                <td align="center">48</td>
                <td align="center">1,024.00</td>
                <td align="center">355.21-1,553.49</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Others</td>
                <td align="center">217</td>
                <td align="center">139.82</td>
                <td align="center">84.39-274.33</td>
                <td align="center">&#160;</td>
                <td align="center">73</td>
                <td align="center">1,378.35</td>
                <td align="center">784.73-2,485.21</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Ambulatory appointment, times</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.002</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.009</td>
              </tr>
              <tr>
                <td align="left">&lt; 5</td>
                <td align="center">192</td>
                <td align="center">168.48</td>
                <td align="center">67.85-321.16</td>
                <td align="center">&#160;</td>
                <td align="center">16</td>
                <td align="center">1,507.97</td>
                <td align="center">984.70-3,821.39</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">6 to 10</td>
                <td align="center">286</td>
                <td align="center">147.90</td>
                <td align="center">79.49-308.74</td>
                <td align="center">&#160;</td>
                <td align="center">16</td>
                <td align="center">1,530.34</td>
                <td align="center">713.99-2,890.81</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">11 to 15</td>
                <td align="center">124</td>
                <td align="center">190.69</td>
                <td align="center">111.44-510.07</td>
                <td align="center">&#160;</td>
                <td align="center">42</td>
                <td align="center">800.50</td>
                <td align="center">446.29-2,232.58</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">16 to 20</td>
                <td align="center">46</td>
                <td align="center">151.78</td>
                <td align="center">89.09-339.14</td>
                <td align="center">&#160;</td>
                <td align="center">28</td>
                <td align="center">905.63</td>
                <td align="center">309.77-1,756.99</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">&#8805; 21</td>
                <td align="center">78</td>
                <td align="center">189.04</td>
                <td align="center">116.25-363.56</td>
                <td align="center">&#160;</td>
                <td align="center">44</td>
                <td align="center">1,445.44</td>
                <td align="center">955.98-2,737.73</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Functional class</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.010</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">I and II</td>
                <td align="center">326</td>
                <td align="center">134.27</td>
                <td align="center">72.15-278.23</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">III and IV</td>
                <td align="center">101</td>
                <td align="center">213.35</td>
                <td align="center">110.97-637.56</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Ethnicity</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.57</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.15</td>
              </tr>
              <tr>
                <td align="left">White and yellow</td>
                <td align="center">564</td>
                <td align="center">169.05</td>
                <td align="center">85.18-339.40</td>
                <td align="center">&#160;</td>
                <td align="center">126</td>
                <td align="center">1,161.89</td>
                <td align="center">573.85-2,432.95</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">Black and mulatto</td>
                <td align="center">148</td>
                <td align="center">157.10</td>
                <td align="center">86.02-391.50</td>
                <td align="center">&#160;</td>
                <td align="center">20</td>
                <td align="center">1,709.93</td>
                <td align="center">800.58-3,134.78</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>LVEF</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.92</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">0.32</td>
              </tr>
              <tr>
                <td align="left">&#8804; 40%</td>
                <td align="center">310</td>
                <td align="center">149.32</td>
                <td align="center">75.75-331.42</td>
                <td align="center">&#160;</td>
                <td align="center">10</td>
                <td align="center">1,133.99</td>
                <td align="center">712.47-2,548.44</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">&gt; 40%</td>
                <td align="center">129</td>
                <td align="center">136.30</td>
                <td align="center">72,65-286.64</td>
                <td align="center">&#160;</td>
                <td align="center">126</td>
                <td align="center">1,203.64</td>
                <td align="center">583.40-2,487.27</td>
                <td align="center">&#160;</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <p>Measurement data are presented as median with interquartile range. LVEF: left ventricular ejection fraction; HF: heart failure; HT: heart transplantation.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Cost via commercial pharmacies according to subgroup analyses</title>
        <p>In the HF group, the monthly median cost for men was $155.34 (IQ 91.30-314.85) and for women $175.21 (IQ 80.68-415.44) (p = 0.412). With respect to comorbidities, an incremental monthly median cost was associated with hypertension (p &lt; 0.001) and diabetes (p &lt; 0.001). Hypertension was responsible for an incremental cost of $60.35 (28% higher) (p = 0.005), and diabetes, for an incremental cost of $130.19 (48% higher) (p &lt; 0.001). The cost of ischemic cardiomyopathy ($200.96, IQ 113.73-447.87) was significantly higher than that of chagasic cardiomyopathy ($138.85, IQ 19.03-303.53, p = 0.003) and other causes ($139.82, IQ 84.39-274.33, p = 0.004). In the multivariate analysis, a significant interactive effect between cost and age was observed for HF patients; not surprisingly, older subjects had significantly higher costs (&#946; = .018, p &lt; 0.001). Men (&#946; = -.165, p &lt; 0.001) and subjects without diabetes had significantly lower costs (&#946; = .568, p = 0.003).</p>
        <p>In the HT group, a tendency toward a lower monthly median cost for prescribed drugs was observed for men ($1,056.83, IQ 532.31-2,325.00) than for women ($1,313.48, IQ 907.33-3,011.20) (p = 0.069). Nevertheless, diabetes was the only comorbidity responsible for an incremental cost of $795.99 (40% higher) (p = 0.045). No difference in cost was observed between causes. Additional parallels between clinical variables and monthly median cost for both groups are shown in <xref ref-type="table" rid="t04">Table 4</xref>. In the HT group, the multivariate analysis showed a significant interactive effect for cost and absence of hypertension (&#946; = -.218, p &lt; 0.001). The absence of hypertension resulted in lower costs in the private system. In this model, there were no statistically significant differences for other variables.</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>To our knowledge, this is the first study to demonstrate that the cost of delivered prescription drugs in HF and HT, patients purchased via RA is remarkably lower than estimated private market costs in the real world scenario of clinical practice. In fact, in this comparison, purchasing via RA for HF followed by delivery to patients is likely a bargain. Older age was associated with higher costs, and the absence of diabetes was associated with lower costs in HF patients via both purchasing systems. The magnitude of cost reduction via RA was higher in diabetes and hypertension (<xref ref-type="fig" rid="f02">Figure 2</xref>).</p>
      <p>Our cost for HF pharmacological treatment was expressively lower in comparison with the previously reported cost, ranging from $261 to $438 per month per patient<xref ref-type="bibr" rid="B09">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>. Actually, the cost of drugs purchased via RA in our investigation ranged from approximately 2.28% to 3.8% of previously published data from the USA, whereas the estimated cost in the private market ranged from 37% to 62%. The USA health system, acknowledged as one of the most expensive in the world with consequently higher prices for medications<xref ref-type="bibr" rid="B15">15</xref>, could contribute for those differences. However, the enormous difference in cost corroborated our findings of the RA effectiveness in reducing costs for HF treatment.</p>
      <p>Regarding HT, the comparison with data of only one published study analyzing the cost of immunosuppressants from solid organ transplantation up to 2 years post-transplantation shows that RA may be proportionally less effective in reducing costs after HT. In that study, costs ranged from $448 to $1,321 per patient per month<xref ref-type="bibr" rid="B16">16</xref>. However, the cost of other medications was not considered, which could underestimate the total cost of pharmacological treatment.</p>
      <p>To explain our results, we would like to speculate that purchasing via RA might create a competitive environment for many industries involved in producing HF medications. The competition, rather than being a disadvantage to industry, would push pharmaceutical manufacturers to improve their business processes to maintain a profit while at the same time benefiting society. Conversely, the small number of industries involved in the production of immunosuppressant drugs and the restricted market may prevent the development of a competitive environment and limit the effectiveness of RA for HT. As a result, the pharmacological therapy for transplantation has a high cost as compared with that for HF<xref ref-type="bibr" rid="B16">16</xref>.</p>
      <p>As expected and confirming published data, comorbidities were associated with a higher cost<xref ref-type="bibr" rid="B08">8</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>. The higher cost for older patients could be explained by the ageing process leading to greater comorbidity. In general, comorbidities require polypharmacy treatment; however, it is worth noting that diabetes was associated with higher incremental costs in HF, probably because of the role of diabetes in the development of many comorbidities<xref ref-type="bibr" rid="B09">9</xref>. However, RA was more effective in diabetes (<xref ref-type="fig" rid="f02">Figure 2</xref>).</p>
      <sec>
        <title>Our findings suggest that RA is a positive alternative for health system</title>
        <p>Our findings suggest that RA is a positive alternative for health system financial support and could be introduced to other countries to reduce the cost of the pharmacological treatment of HF and after HT. People involved in medication supply for HF should reflect about the possibility of purchase via RA and delivery to patients. The cost of outpatient medications may influence the patients' adherence to recommended pharmacological treatment<xref ref-type="bibr" rid="B10">10</xref>. The lower cost could result in greater access to pharmacological treatment with greater adherence to prescribed medications, better survival and less hospitalization. The worldwide use of RA to health policies could benefit many people in developed and mainly undeveloped countries, reducing the economic burden of HF.</p>
      </sec>
      <sec>
        <title>Limitations</title>
        <p>Our study has limitations. We assessed only prescribed and delivered drugs; consequently, we were unable to ascertain patient adherence. However, it is sufficient to demonstrate how much pharmacological therapy occurs in clinical practice. The regimens administered to the patients were based on those prescribed by specialized cardiologists at a tertiary center and may not represent primary care in HF treatment. Our single-center study did not include patients from multiple practices and diverse Brazilian geographic regions; however, in these conditions, the pharmacological treatment is not usually guideline-oriented. Finally, our study was a retrospective review of medical records, because a prospective study would require more time and economic resources.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>In the present study in contemporary practice, we were able to demonstrate that RA may be valuable as a potential tool for reducing HF burden dependent on the pharmacological therapy cost of HF outpatients and after HT. In addition, the prevalence of comorbidities and older age are associated with higher cost, which should be considered in planning health strategies for HF. Likewise, the key finding is that RA could become a government strategy to extend drug therapy access to less socially privileged people and in the optimal use of public resources.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title>Preg&#227;o: Estrat&#233;gia para Redu&#231;&#227;o do Custo da Terapia Farmacol&#243;gica em Insufici&#234;ncia Card&#237;aca e Transplante Card&#237;aco</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Brand&#227;o</surname>
            <given-names>Sara Michelly Gon&#231;alves</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Issa</surname>
            <given-names>Victor Sarli</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ayub-Ferreira</surname>
            <given-names>Silvia Moreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Storer</surname>
            <given-names>Samantha</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gon&#231;alves</surname>
            <given-names>Bianca Gigliotti</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Valter Garcia</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carvas</surname>
            <given-names>Nelson</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Guilherme Veiga</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bocchi</surname>
            <given-names>Edimar Alcides</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff02">
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <addr-line>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, SP - Brasil</institution>
        <institution content-type="normalized">Universidade de S&#227;o Paulo</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Correspond&#234;ncia: Sara Michelly Gon&#231;alves Brand&#227;o</bold>, Av. Brigadeiro Lu&#237;s Ant&#244;nio, 1195 Ap 22, Bela Vista. CEP 01317001, S&#227;o Paulo, SP &#8211; Brasil. E-mail: <email>saramichelly_brandao@yahoo.com.br</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Brand&#227;o SMG, Bocchi EA. Obten&#231;&#227;o de dados: Brand&#227;o SMG, Storer S, Gon&#231;alves BG, Santos VG. An&#225;lise e interpreta&#231;&#227;o dos dados: Brand&#227;o SMG. An&#225;lise estat&#237;stica: Brand&#227;o SMG, Carvas Junior N. Reda&#231;&#227;o do manuscrito: Brand&#227;o SMG, Bocchi EA. Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Brand&#227;o SMG, Issa VS, Ayub-Ferreira SM, Guimar&#227;es GV, Bocchi EA.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <sec>
          <title>Fundamento:</title>
          <p>A polifarm&#225;cia tem um significativo peso econ&#244;mico.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Testar se o uso de preg&#227;o em compara&#231;&#227;o ao de farm&#225;cias comerciais (FC) para a compra de medicamentos reduz o custo do tratamento de pacientes ambulatoriais de insufici&#234;ncia card&#237;aca (IC) e transplante card&#237;aco (TC).</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Compara&#231;&#227;o dos custos do tratamento atrav&#233;s de preg&#227;o versus FC em pacientes de IC (808) e TC (147) acompanhados de 2009 a 2011, avaliando-se a influ&#234;ncia de vari&#225;veis cl&#237;nicas e demogr&#225;ficas no custo.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Os custos mensais por paciente para medicamentos de IC adquiridos atrav&#233;s de preg&#227;o e atrav&#233;s de FC foram $10,15 (IQ 3,51-40,22) e $161,76 (IQ 86,05-340,15), respectivamente. Para TC, aqueles custos foram $393,08 (IQ 124,74-774,76) e $1.207,70 (IQ 604,48-2.499,97), respectivamente.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>O preg&#227;o pode reduzir o custo dos medicamentos prescritos para IC e TC, podendo tornar o tratamento de IC mais acess&#237;vel. As caracter&#237;sticas cl&#237;nicas podem influenciar o custo e os benef&#237;cios do preg&#227;o, que pode ser uma nova estrat&#233;gia de pol&#237;tica de sa&#250;de para baixar os custos dos medicamentos prescritos para IC e TC, diminuindo o peso econ&#244;mico do tratamento. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0)</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Prepara&#231;&#245;es Farmac&#234;uticas / economia</kwd>
        <kwd>Proposta de Concorr&#234;ncia / economia</kwd>
        <kwd>Or&#231;amentos</kwd>
        <kwd>Redu&#231;&#227;o de Custos</kwd>
        <kwd>Transplante de Cora&#231;&#227;o</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>O n&#250;mero estimado de pacientes com insufici&#234;ncia card&#237;aca (IC) nos Estados Unidos da Am&#233;rica (EUA) &#233; de 5,1 milh&#245;es<xref ref-type="bibr" rid="B01">1</xref> e, no Brasil, 6,4 milh&#245;es<xref ref-type="bibr" rid="B02">2</xref>. A IC foi a causa &#250;nica mais frequente de hospitaliza&#231;&#227;o na popula&#231;&#227;o idosa no Brasil<xref ref-type="bibr" rid="B02">2</xref>. A observ&#226;ncia das diretrizes de terapia farmacol&#243;gica para IC reduz a progress&#227;o da doen&#231;a, sua morbimortalidade e hospitaliza&#231;&#227;o<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref>. Os gastos p&#250;blicos e privados com medicamentos s&#227;o respons&#225;veis por uma substancial fra&#231;&#227;o do total de despesas com cuidados de sa&#250;de nos pa&#237;ses desenvolvidos e em desenvolvimento<xref ref-type="bibr" rid="B05">5</xref>. Nos EUA, estima-se para 2015 um custo de $32,4 bilh&#245;es para a IC, uma doen&#231;a cardiovascular<xref ref-type="bibr" rid="B06">6</xref>. Cerca de 3% do custo total com IC deu-se com medicamentos, somando aproximadamente $1,11 bilh&#227;o em 2009<xref ref-type="bibr" rid="B07">7</xref>. &#233; de surpreender que, a despeito do impacto influ&#234;ncia de caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas<xref ref-type="bibr" rid="B08">8</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref>. Al&#233;m disso, esse limitado n&#250;mero de estudos n&#227;o reflete a pr&#225;tica contempor&#226;nea. Nenhum estudo pr&#233;vio examinou a influ&#234;ncia de procedimentos adicionais, como o transplante card&#237;aco (TC).</p>
        <p>Os recursos em sa&#250;de s&#227;o escassos, ainda que as necessidades na &#225;rea sejam ilimitadas. &#233; importante ressaltar que estrat&#233;gias para a redu&#231;&#227;o do custo do tratamento farmacol&#243;gico na IC n&#227;o foram testadas, a despeito do impacto tanto do custo dos medicamentos nos or&#231;amentos do governo quanto da n&#227;o observ&#226;ncia do uso dos medicamentos. Estudos concernentes a tratamentos farmacol&#243;gicos e seus custos podem fornecer uma base l&#243;gica para que pol&#237;ticas governamentais planejem fontes de financiamento, sendo essenciais para a farmacoeconomia em sa&#250;de p&#250;blica. Portanto, este estudo teve por objetivo comparar os custos do tratamento farmacol&#243;gico para IC e TC atrav&#233;s de preg&#245;es com aqueles estimados nas farm&#225;cias comerciais (FC).</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Popula&#231;&#227;o do estudo</title>
          <p>Foram obtidos retrospectivamente os dados cl&#237;nicos, demogr&#225;ficos e de tratamento farmacol&#243;gico de todos os pacientes com diagn&#243;stico de IC ou dos receptores de TC consecutivamente atendidos no Ambulat&#243;rio de Insufici&#234;ncia Card&#237;aca do Instituto do Cora&#231;&#227;o no Brasil. Os dados demogr&#225;ficos inclu&#237;ram etnia descrita em estudo anterior<xref ref-type="bibr" rid="B13">13</xref>, idade, sexo, comorbidade e causa de IC descritos em estudo anterior<xref ref-type="bibr" rid="B13">13</xref>, fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda (FEVE), n&#250;mero de consultas ambulatoriais, medicamentos e os est&#225;gios de IC mais comuns durante o per&#237;odo estudado. Obteve-se a FEVE usando-se um dos seguintes m&#233;todos: ecocardiografia, ventriculografia radioisot&#243;pica, resson&#226;ncia magn&#233;tica card&#237;aca ou ventriculografia por cateteriza&#231;&#227;o card&#237;aca. Considerou-se a primeira FEVE de cada paciente no per&#237;odo estudado. Os pacientes foram atendidos por m&#233;dicos e uma equipe multidisciplinar especializada em IC e TC de janeiro de 2009 a abril de 2011. Inclu&#237;ram-se os pacientes com mais de 16 anos e em acompanhamento ambulatorial, exceto um de TC com 9 anos. Exclu&#237;ram-se os pacientes com informa&#231;&#227;o incompleta cl&#237;nica ou de custo e que tenham recebido a prescri&#231;&#227;o de qualquer medicamento durante hospitaliza&#231;&#227;o.</p>
        </sec>
        <sec>
          <title>Delineamento do estudo</title>
          <p>Os dados concernentes &#224;s consultas ambulatoriais foram armazenados em registros eletr&#244;nicos, de modo a gerar automaticamente uma prescri&#231;&#227;o m&#233;dica eletr&#244;nica a partir da entrada dos dados. Os medicamentos foram dispensados mensalmente aos pacientes de acordo com a &#250;ltima prescri&#231;&#227;o m&#233;dica validada. Obtivemos informa&#231;&#227;o a respeito de todos os medicamentos que cada paciente recebeu, tendo os investigadores revisado tal informa&#231;&#227;o para garantir consist&#234;ncia.</p>
          <p>Na nossa institui&#231;&#227;o, que &#233; p&#250;blica, os medicamentos s&#227;o comprados atrav&#233;s de preg&#245;es. Trata-se de mecanismo atrav&#233;s do qual, uma vez consolidada a demanda das entidades participantes e estabelecidas as caracter&#237;sticas t&#233;cnicas dos produtos a serem comprados, aqueles com o melhor pre&#231;o s&#227;o selecionados atrav&#233;s de lances eletr&#244;nicos pelo menor valor. Isso garante uma competi&#231;&#227;o justa e transparente, e ainda os menores pre&#231;os de mercado, especialmente nos pa&#237;ses da Am&#233;rica Latina, como o Brasil. As compras s&#227;o financiadas por um or&#231;amento anual destinado a cada institui&#231;&#227;o p&#250;blica atrav&#233;s de fundos p&#250;blicos de sa&#250;de. Nos preg&#245;es para aquisi&#231;&#227;o de medicamentos, os fornecedores prop&#245;em um contrato bastante detalhado de suprimento, especificando o medicamento, sua quantidade e local e programa de entrega<xref ref-type="bibr" rid="B14">14</xref>.</p>
          <p>O contrato de aquisi&#231;&#227;o especifica detalhadamente o medicamento a ser fornecido, que &#233; uma combina&#231;&#227;o &#250;nica de princ&#237;pio ativo, forma, concentra&#231;&#227;o, n&#250;mero de unidades e embalagem. As institui&#231;&#245;es p&#250;blicas s&#227;o proibidas de adquirir um medicamento de uma marca espec&#237;fica. S&#227;o obrigadas a adquiri-lo do fornecedor de menor pre&#231;o, podendo, em princ&#237;pio, ser gen&#233;rico ou de marca<xref ref-type="bibr" rid="B14">14</xref>.</p>
          <p>Os medicamentos s&#227;o dispensados gratuitamente para os pacientes tratados em hospital p&#250;blico conforme a prescri&#231;&#227;o. Comparamos o tratamento farmacol&#243;gico da IC e do TC comprado atrav&#233;s de preg&#227;o com os custos estimados no mercado privado de FC. O pre&#231;o de FC foi definido usando-se o Guia Farmac&#234;utico Bras&#237;ndice, um &#237;ndice federal oficial que regula o mercado de medicamentosno Brasil (custo privado): o governo brasileiro estabelece o pre&#231;o de varejo m&#225;ximo praticado pelas farm&#225;cias. O custo de cada comprimido foi baseado na &#250;ltima compra institucional em 2011 para evitar diferen&#231;as de pre&#231;o entre per&#237;odos de tempo. O valor de custo foi convertido em d&#243;lares americanos de acordo com a cota&#231;&#227;o de 12 de abril de 2013 a uma taxa de c&#226;mbio de $0,50815 para estabelecer os valores em uma moeda est&#225;vel. Calculou-se o custo mensal por paciente.</p>
          <p>Os medicamentos inclu&#237;dos foram betabloqueadores, diur&#233;ticos, bloqueadores dos canais de c&#225;lcio (BCC), inibidores da enzima de convers&#227;o da angiotensina (IECA), bloqueadores do receptor de angiotensina (BRA), outros medicamentos cardiovasculares (OMC), hipolipemiantes, antiagregantes plaquet&#225;rios, antiarr&#237;tmicos, nitratos, anticoagulantes (ACG) ou inibidores do receptor adenosina difosfato plaquet&#225;rio (IPADPR), digit&#225;licos, imunossupressores e outros medicamentos n&#227;o cardiovasculares (OMNC). Os medicamentos tipicamente usados para tratamentos curtos, como antibi&#243;ticos, ou aqueles de uso conforme necessidade para al&#237;vio de sintomas, como analg&#233;sicos ou nitroglicerina sublingual, tamb&#233;m foram inclu&#237;dos.</p>
          <p>Analisamos ainda os custos conforme as vari&#225;veis cl&#237;nicas e demogr&#225;ficas. O protocolo de estudo foi aprovado pelo Comit&#234; de &#233;tica do Instituto do Cora&#231;&#227;o de S&#227;o Paulo (registro 22831813.2.0000.0068), tendo-se dispensado o termo de consentimento, pois n&#227;o houve identifica&#231;&#227;o da informa&#231;&#227;o dos participantes.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>As medidas foram expressas como m&#233;dia &#177; desvio padr&#227;o (DP) para as vari&#225;veis com distribui&#231;&#227;o normal, e como mediana e intervalo interquartil (IQ) para aquelas sem distribui&#231;&#227;o normal, ou ainda como frequ&#234;ncias em percentagens para todas as vari&#225;veis categ&#243;ricas. Realizou-se an&#225;lise univariada com o teste do qui-quadrado ou exato de Fisher para comparar as vari&#225;veis categ&#243;ricas. As cont&#237;nuas com distribui&#231;&#227;o normal foram comparadas usando-se o teste   <italic>t</italic> de Student, e, para avaliar as diferen&#231;as entre aquelas sem distribui&#231;&#227;o normal, usou-se o teste de Kruskal-Wallis. A signific&#226;ncia dos resultados do teste de Kruskal-Wallis foi analisada usando-se o teste da diferen&#231;a m&#237;nima significativa (DMS) com m&#250;ltiplas compara&#231;&#245;es <italic>post hoc</italic>. Para determinar a correla&#231;&#227;o entre as vari&#225;veis cont&#237;nuas, aplicou-se o teste de correla&#231;&#227;o conforme a distribui&#231;&#227;o de normalidade (<italic>r</italic>). A FEVE foi analisada em coortes estratificadas em &#8804; 40% e &gt; 40%.</p>
          <p>O custo mensal por paciente foi submetido a transforma&#231;&#227;o logar&#237;tmica. Realizou-se an&#225;lise multivariada com equa&#231;&#245;es de estima&#231;&#227;o generalizada (GEE ), sendo os resultados expressos como coeficientes n&#227;o padronizados (&#946;). As GEE foram aplicadas, usando-se as vari&#225;veis cont&#237;nuas (idade, FEVE e consulta ambulatorial) e a vari&#225;vel categ&#243;rica 'causa de IC' como efeitos fixos. Comorbidades, classe funcional, etnia e sexo foram usados como efeitos rand&#244;micos. A vantagem dessa abordagem foi ter utilizado todos os dados dispon&#237;veis e resultados baseados em correla&#231;&#245;es entre desfechos e vari&#225;veis preditivas. Usou-se o teste do qui-quadrado de Wald para escolher a melhor estrutura a ser adotada no modelo em quest&#227;o. Usou-se ainda o teste de quase-verossimilhan&#231;a para comparar modelos ajustados.</p>
          <p>O programa SPSS 17.0 foi utilizado para a an&#225;lise estat&#237;stica. Os valores de p &lt; 0,05 foram considerados significativos, e aqueles &lt; 0,10, uma tend&#234;ncia.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Caracter&#237;sticas basais (<xref ref-type="table" rid="t05">Tabela 1</xref>)</title>
          <table-wrap id="t05">
            <label>Tabela 1</label>
            <caption>
              <title> Caracter&#237;sticas basais da popula&#231;&#227;o do estudo</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th align="left">
                    <bold>CARACTER&#205;STICAS</bold>
                  </th>
                  <th align="center">
                    <bold>IC n = 808 n (%)</bold>
                  </th>
                  <th align="center">
                    <bold>TC n = 147 n (%)</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">
                    <bold>Idade, anos</bold>
                  </td>
                  <td align="center">56,5 &#177; 12,2</td>
                  <td align="center">49,9 &#177; 16,6</td>
                </tr>
                <tr>
                  <td align="left">&lt; 20</td>
                  <td align="center">5(0,6)</td>
                  <td align="center">9(6,1)</td>
                </tr>
                <tr>
                  <td align="left">20 - 40</td>
                  <td align="center">80 (9,9)</td>
                  <td align="center">37 (25,2)</td>
                </tr>
                <tr>
                  <td align="left">41 - 65</td>
                  <td align="center">427 (52,8)</td>
                  <td align="center">57 (11,8)</td>
                </tr>
                <tr>
                  <td align="left">&#8805; 66</td>
                  <td align="center">296 (36,6)</td>
                  <td align="center">44 (29,9)</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Consulta ambulatorial</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">&lt; 5</td>
                  <td align="center">250 (30,9)</td>
                  <td align="center">16 (10,9)</td>
                </tr>
                <tr>
                  <td align="left">6 - 10</td>
                  <td align="center">302 (37,4)</td>
                  <td align="center">17 (11,6)</td>
                </tr>
                <tr>
                  <td align="left">11 - 15</td>
                  <td align="center">127 (15,7)</td>
                  <td align="center">42 (28,6)</td>
                </tr>
                <tr>
                  <td align="left">16 - 20</td>
                  <td align="center">48 (5,9)</td>
                  <td align="center">28 (19,0)</td>
                </tr>
                <tr>
                  <td align="left">&#8805; 21</td>
                  <td align="center">81 (10,0)</td>
                  <td align="center">44 (29,9)</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Etnia</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Branca e amarela</td>
                  <td align="center">619 (78,3)</td>
                  <td align="center">127 (86,4)</td>
                </tr>
                <tr>
                  <td align="left">Negra e parda</td>
                  <td align="center">172 (21,7)</td>
                  <td align="center">20 (13,6)</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Causas</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Isqu&#233;mica</td>
                  <td align="center">141 (30,7)</td>
                  <td align="center">18 (12,9)</td>
                </tr>
                <tr>
                  <td align="left">Outras</td>
                  <td align="center">232 (50,5)</td>
                  <td align="center">73 (52,5)</td>
                </tr>
                <tr>
                  <td align="left">Chag&#225;sica</td>
                  <td align="center">86 (18,7)</td>
                  <td align="center">48 (34,5)</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Sexo</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Masculino</td>
                  <td align="center">508 (62,9)</td>
                  <td align="center">101 (68,7)</td>
                </tr>
                <tr>
                  <td align="left">Feminino</td>
                  <td align="center">300 (37,1)</td>
                  <td align="center">46 (31,3)</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Comorbidades</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Hipertens&#227;o</td>
                  <td align="center">157 (19,5)</td>
                  <td align="center">40 (27,2)</td>
                </tr>
                <tr>
                  <td align="left">Diabetes</td>
                  <td align="center">150 (18,6)</td>
                  <td align="center">30 (20,4)</td>
                </tr>
                <tr>
                  <td align="left">Acidente vascular cerebral</td>
                  <td align="center">31 (3,9)</td>
                  <td align="center">5 (3,4)</td>
                </tr>
                <tr>
                  <td align="left">Insufici&#234;ncia renal</td>
                  <td align="center">56 (7,0)</td>
                  <td align="center">18 (12,2)</td>
                </tr>
                <tr>
                  <td align="left">DPOC</td>
                  <td align="center">13 (1,6)</td>
                  <td align="center">2 (1,4)</td>
                </tr>
                <tr>
                  <td align="left">Revasculariza&#231;&#227;o mioc&#225;rdica</td>
                  <td align="center">20 (2,5)</td>
                  <td align="center">0 (0,0)</td>
                </tr>
                <tr>
                  <td align="left">Angioplastia coronariana</td>
                  <td align="center">9(1,1)</td>
                  <td align="center">2 (1,4)</td>
                </tr>
                <tr>
                  <td align="left">Infarto do mioc&#225;rdio</td>
                  <td align="center">56 (7,0)</td>
                  <td align="center">4 (2,7)</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Medicamento cardiovascular prescrito</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Betabloqueador</td>
                  <td align="center">703 (87,1)</td>
                  <td align="center">40 (27,2)</td>
                </tr>
                <tr>
                  <td align="left">Diur&#233;tico</td>
                  <td align="center">703 (87,1)</td>
                  <td align="center">54 (36,7)</td>
                </tr>
                <tr>
                  <td align="left">BCC</td>
                  <td align="center">205 (25,4)</td>
                  <td align="center">114 (77,6)</td>
                </tr>
                <tr>
                  <td align="left">IECA, BRA</td>
                  <td align="center">573 (71,0)</td>
                  <td align="center">54 (36,7)</td>
                </tr>
                <tr>
                  <td align="left">Hipolipemiante</td>
                  <td align="center">595 (73,7)</td>
                  <td align="center">117 (79,6)</td>
                </tr>
                <tr>
                  <td align="left">Antiagregante plaquet&#225;rio</td>
                  <td align="center">354 (43,9)</td>
                  <td align="center">30 (20,4)</td>
                </tr>
                <tr>
                  <td align="left">ACG ou IPADPR</td>
                  <td align="center">212 (26,3)</td>
                  <td align="center">20 (13,6)</td>
                </tr>
                <tr>
                  <td align="left">Antiarr&#237;tmicos</td>
                  <td align="center">85 (10,5)</td>
                  <td align="center">4 (2,7)</td>
                </tr>
                <tr>
                  <td align="left">Digit&#225;lico</td>
                  <td align="center">309 (38,3)</td>
                  <td align="center">15 (10,2)</td>
                </tr>
                <tr>
                  <td align="left">Nitrato</td>
                  <td align="center">197 (24,4)</td>
                  <td align="center">11 (7,5)</td>
                </tr>
                <tr>
                  <td align="left">OMC</td>
                  <td align="center">330 (40,9)</td>
                  <td align="center">47 (32,0)</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Medicamento n&#227;o cardiovascular prescrito</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Antibi&#243;tico</td>
                  <td align="center">42 (5,2)</td>
                  <td align="center">68 (46,3)</td>
                </tr>
                <tr>
                  <td align="left">Imunossupressor</td>
                  <td align="center">0 (0)</td>
                  <td align="center">147 (100)</td>
                </tr>
                <tr>
                  <td align="left">OMNC</td>
                  <td align="center">630 (78,1)</td>
                  <td align="center">147 (100)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN5">
                <p>IC: insufici&#234;ncia card&#237;aca; TC: transplante card&#237;aco; DPOC: doen&#231;a pulmonar obstrutiva cr&#244;nica; ACG: anticoagulante; IPADPR: inibidor do receptor ADPplaquet&#226;rio; OMNC: outros medicamentos n&#227;o cardiovasculares; betabloqueador (atenolol, bisoprolol, metoprolol, carvedilol, propranolol, sotalol); diur&#233;tico (furosemida, hidroclorotiazida, clortalidona, espironolactona); BCC: bloqueador do canal de c&#225;lcio (diltiazem, verapamil, anlodipino, nifedipina, losartana); IECA: inibidor da enzima de convers&#227;o da angiotensina (captopril, enalapril, lisinopril); BRA: bloqueador do receptor da angiotensina, hipolipemiante (atorvastatina, ciprofibrato, ezetimiba, rosuvastatina, sinvastatina); antiagregante plaquet&#225;rio (aspirina); ACG ou IPADPR (enoxaparina, varfarina, clopidogrel); antiarr&#237;tmicos (amiodarona, propafenona); digit&#225;lico (digoxina); nitrato (isossorbida, propatilnitrato); OMC: outros medicamentos cardiovasculares (clonidina, doxazosina, hidralazina, metildopa).</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>No grupo IC, o tempo m&#233;dio de seguimento no estudo foi de 16,7 &#177; 8,8 meses, com uma mediana de oito consultas ambulatoriais por paciente, enquanto no grupo TC o tempo m&#233;dio de seguimento foi de 23,1 &#177; 5,8 meses, com uma mediana de 16 consultas ambulatoriais por paciente. O total de prescri&#231;&#245;es m&#233;dicas analisadas no grupo IC foi de 8.448, e, no grupo TC, 3.217. Informa&#231;&#227;o completa de custo n&#227;o p&#244;de ser obtida em 82 (10,1%) pacientes com IC, e em 1 (0,7%) receptor de TC, tendo esses pacientes sido exclu&#237;dos. As consultas ambulatoriais foram mais frequentes entre pacientes com classe funcional de IC III e IV do que entre aqueles com classe funcional I e II. Os pacientes com classe funcional III e IV apresentaram as seguintes causas de IC: chag&#225;sica, 26,8%; isqu&#234;mica, 34,1%; e outras, 39%. Para aqueles com classe funcional I e II, as propor&#231;&#245;es foram 12,9%, 29,6% e 57,5%, respectivamente (p = 0,003).</p>
        </sec>
        <sec>
          <title>Medicamentos prescritos para IC</title>
          <p>Os medicamentos mais frequentemente prescritos em ordem decrescente foram betabloqueadores, diur&#233;ticos, OMNC, hipolipemiantes, IECA-BRA (<xref ref-type="table" rid="t05">Tabela 1</xref>). Observou-se uma diferen&#231;a quanto aos medicamentos prescritos para pacientes com FEVE &#8804; 40% e para aqueles com FEVE &gt; 40%. Betabloqueadores, diur&#233;ticos, antiagregantes plaquet&#225;rios, antiarr&#237;tmicos e nitratos foram mais frequentemente prescritos para pacientes com IC e FEVE &#8804; 40%, enquanto BCC foram mais frequentemente prescritos para pacientes com IC e FEVE &gt; 40% (<xref ref-type="table" rid="t06">Tabela 2</xref>). Betabloqueadores (75,9%, p = 0,009), diur&#233;ticos (75,9%, p = 0,009), IECA-BRA (76,6%, p = 0,034), nitrato (61,9%, p = 0,001) e OMC (68,8%, p = 0,036) foram mais frequentemente prescritos para pacientes com classe funcional de IC I e II. Pacientes de etnia branca e amarela receberam mais frequentemente OMC (74,1%, p = 0,015) e antiagregantes plaquet&#225;rios (82,2%, p = 0,018). Os BCC (60.3%, p &lt; 0.001) e hipolipemiantes (47%, p &lt; 0,001) foram mais frequentemente prescritos para outras causas, enquanto antiagregantes plaquet&#225;rios (53,3%, p &lt; 0,001) e nitratos (43%, p &lt; 0,001) foram mais frequentemente prescritos para pacientes isqu&#234;micos, e antiarr&#237;tmicos (41%, p &lt; 0,001) para pacientes chag&#225;sicos. Os IECA-BRA (33,3%, p = 0,001), OMC (42,1%, p = 0,013), antiagregantes plaquet&#225;rios (31,4%, p = 0,003) e OMNC (40,2%, p = 0,001) foram prescritos com menos frequ&#234;ncia para mulheres.</p>
          <table-wrap id="t06">
            <label>Tabela 2</label>
            <caption>
              <title>Perfil do medicamento prescrito de acordo com a fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda (FEVE)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th rowspan="2">
                    <bold>Medicamento prescrito</bold>
                  </th>
                  <th colspan="3" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>IC</bold>
                  </th>
                  <th colspan="3" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>TC</bold>
                  </th>
                </tr>
                <tr>
                  <th align="center">
                    <bold>FEVE &#8804; 40% (n = 321) n (%)</bold>
                  </th>
                  <th align="center">
                    <bold>FEVE &gt; 40% (n = 134) n (%)</bold>
                  </th>
                  <th align="center">
                    <bold>p</bold>
                  </th>
                  <th align="center">
                    <bold>FEVE &#8804; 40% (n = 10) n(%)</bold>
                  </th>
                  <th align="center">
                    <bold>FEVE &gt; 40% (n = 126) n (%)</bold>
                  </th>
                  <th align="center">
                    <bold>p</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Betabloqueador</td>
                  <td align="center">287 (89,4)</td>
                  <td align="center">109(81,3)</td>
                  <td align="center">0,020</td>
                  <td align="center">5 (50,0)</td>
                  <td align="center">32 (25,4)</td>
                  <td align="center">0,13</td>
                </tr>
                <tr>
                  <td align="left">Diur&#233;tico</td>
                  <td align="center">287(89,4)</td>
                  <td align="center">109(81,3)</td>
                  <td align="center">0,020</td>
                  <td align="center">4(40,0)</td>
                  <td align="center">48(38,1)</td>
                  <td align="center">1,00</td>
                </tr>
                <tr>
                  <td align="left">BCC</td>
                  <td align="center">67(20,9)</td>
                  <td align="center">43(32,1)</td>
                  <td align="center">0,011</td>
                  <td align="center">7(70,0)</td>
                  <td align="center">102(81,0)</td>
                  <td align="center">0,41</td>
                </tr>
                <tr>
                  <td align="left">IECA, BRA</td>
                  <td align="center">221(68,8)</td>
                  <td align="center">90(67,2)</td>
                  <td align="center">0,72</td>
                  <td align="center">6(60,0)</td>
                  <td align="center">46(36,5)</td>
                  <td align="center">0,18</td>
                </tr>
                <tr>
                  <td align="left">OCD</td>
                  <td align="center">153(47,7)</td>
                  <td align="center">55(41,0)</td>
                  <td align="center">0,19</td>
                  <td align="center">5(50,0)</td>
                  <td align="center">41(32,5)</td>
                  <td align="center">0,30</td>
                </tr>
                <tr>
                  <td align="left">Hipolipemiante</td>
                  <td align="center">241(75,1)</td>
                  <td align="center">89(27,0)</td>
                  <td align="center">0,059</td>
                  <td align="center">7(70,0)</td>
                  <td align="center">106(84,1)</td>
                  <td align="center">0,37</td>
                </tr>
                <tr>
                  <td align="left">Antiagregante plaquet&#225;rio</td>
                  <td align="center">154(48,0)</td>
                  <td align="center">44(32,8)</td>
                  <td align="center">0,003</td>
                  <td align="center">3(30,0)</td>
                  <td align="center">24(19,0)</td>
                  <td align="center">0,41</td>
                </tr>
                <tr>
                  <td align="left">ACG ou IPADPR</td>
                  <td align="center">93(29,0)</td>
                  <td align="center">39(29,1)</td>
                  <td align="center">0,97</td>
                  <td align="center">1(10,0)</td>
                  <td align="center">19(15,1)</td>
                  <td align="center">1,00</td>
                </tr>
                <tr>
                  <td align="left">Antiarr&#237;tmicos</td>
                  <td align="center">44(13,7)</td>
                  <td align="center">9(6,7)</td>
                  <td align="center">0,034</td>
                  <td align="center">0(0,0)</td>
                  <td align="center">3(100)</td>
                  <td align="center">NP</td>
                </tr>
                <tr>
                  <td align="left">Digit&#225;lico</td>
                  <td align="center">127(39,6)</td>
                  <td align="center">44(32,8)</td>
                  <td align="center">0,17</td>
                  <td align="center">0(0,0)</td>
                  <td align="center">15(11,9)</td>
                  <td align="center">NP</td>
                </tr>
                <tr>
                  <td align="left">Nitrato</td>
                  <td align="center">104(32,4)</td>
                  <td align="center">24(17,9)</td>
                  <td align="center">0,002</td>
                  <td align="center">3(30,0)</td>
                  <td align="center">7(5,6)</td>
                  <td align="center">0,026</td>
                </tr>
                <tr>
                  <td align="left">Antibi&#243;tico</td>
                  <td align="center">25(7,8)</td>
                  <td align="center">7(5,2)</td>
                  <td align="center">0,33</td>
                  <td align="center">5(50,0)</td>
                  <td align="center">62(49,2)</td>
                  <td align="center">1,00</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN6">
                <p>HF: insufici&#234;ncia card&#237;aca; HT: transplante card&#237;aco; NP: n&#227;o poss&#237;vel; ACG: anticoagulante; IPADPR: inibidor do receptor adenosina difosfato plaquet&#225;rio; betabloqueador (atenolol, bisoprolol, metoprolol, carvedilol, propranolol, sotalol); diur&#233;tico (furosemida, hidroclorotiazida, clortalidona, espironolactona); BCC: bloqueador do canal de c&#225;lcio (diltiazem, verapamil, anlodipino, nifedipina, losartana); IECA: inibidor da enzima de convers&#227;o da angiotensina (captopril, enalapril, lisinopril); BRA: bloqueador do receptor da angiotensina; OMC: outros medicamentos cardiovasculares (clonidina, doxazosina, hidralazina, metildopa); hipolipemiante (atorvastatina, ciprofibrato, ezetimiba, rosuvastatina, sinvastatina); antiagregante plaquet&#225;rio (aspirina); ACG ou IPADPR (enoxaparina, varfarina, clopidogrel); antiarr&#237;tmicos (amiodarona, propafenona); digit&#225;lico (digoxina); nitrato (isossorbida, propatilnitrato).</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>No grupo IC, os homens consumiram doses mais baixas de atenolol, captopril, losartana, espironolactona e isossorbida, e mais altas de carvedilol e hidralazina, mas doses iguais de enalapril, embora as doses dos medicamentos de uso di&#225;ria n&#227;o tenham apresentado diferen&#231;a estatisticamente significativa entre os sexos. Com rela&#231;&#227;o &#224; classe funcional, as medianas das doses de enalapril para as classes funcionais III e IV e ainda para I e II foram 30,28 mg/dia (IQ 14,12-35,79) e 33,85 mg/dia (IQ 22,00-38,67), respectivamente (p = 0,014). As medianas das doses de captopril foram 39,58 mg/dia (IQ 13,54-107,29) e 77,52 mg/dia (IQ 43,23-146,42), respectivamente (p = 0,059). Com rela&#231;&#227;o &#224; etnia, negros e pardos usaram mais enalapril (35,42 mg/dia, IQ 23,61-39,27) do que brancos e amarelos (32,93 mg/dia, IQ 18,33-37,78) (p = 0,039). Com rela&#231;&#227;o &#224; idade, pacientes com IC entre 41 e 65 anos receberam com mais frequ&#234;ncia enalapril (34,29 mg/dia, IQ 20,21-38,65, p = 0,019) e espironolactona (25,93 mg/dia, IQ 24,24-30,56, p = 0,049), e tenderam a maiores doses de carvedilol (48,08 mg/dia, IQ 35,04-62,50, p = 0,076) e captopril (93,05 mg/dia, IQ 66,67-145,4, p = 0,087). Com rela&#231;&#227;o &#224; causa, menores doses de carvedilol (42,11 mg/dia, IQ 25,00-50,00, p &lt; 0,001) e de enalapril (23,33 mg/dia, IQ 14,44-32,22, p &lt; 0,001) foram administradas a pacientes chag&#225;sicos em compara&#231;&#227;o a isqu&#234;micos e com cardiopatias por outras causas. Menores doses de losartana (85,55 mg/dia, IQ 52,77-100,00, p = 0,021) foram administradas a chag&#225;sicos e isqu&#234;micos em compara&#231;&#227;o &#224;queles com cardiopatia por outras causas. As correla&#231;&#245;es entre consumo di&#225;rio de carvedilol e FEVE foram fracas (r = 0,125, p = 0,017).</p>
          <p>No grupo TC, os medicamentos mais frequentemente prescritos foram imunossupressores, OMNC, hipolipemiantes e BCC (<xref ref-type="table" rid="t05">Tabela 1</xref>). Al&#233;m disso, houve diferen&#231;a quanto ao uso de nitratos entre pacientes com FEVE &#8804;40% e aqueles com FEVE &gt; 40% (p = 0,026) (<xref ref-type="table" rid="t06">Tabela 2</xref>). Pacientes de etnia branca e amarela receberam mais antibi&#243;ticos (77,9%, p = 0,006). No que se refere &#224; causa, os medicamentos usados n&#227;o apresentaram diferen&#231;as estatisticamente significativas. Com rela&#231;&#227;o a sexo, os antibi&#243;ticos foram mais frequentemente usados por homens do que por mulheres (58,8%, p = 0,016). A <xref ref-type="fig" rid="f03">Figura 1</xref> mostra a magnitude da redu&#231;&#227;o de custo para medicamentos comprados atrav&#233;s do preg&#227;o.</p>
          <fig id="f03">
            <label>Figura 1</label>
            <caption>
              <title>Redu&#231;&#227;o do custo (percentagem) dos medicamentos prescritos e dispensados, comprados por preg&#227;o em compara&#231;&#227;o aos custos no mercado privado de acordo com cada grupo de medicamento para insufici&#234;ncia card&#237;aca (superior) e transplante card&#237;aco (inferior). Imunossup: imunossupressores; OMNC: outros medicamentos n&#227;o cardiovasculares; BCC: bloqueadores do canal de c&#225;lcio; IECA: inibidores da enzima de convers&#227;o da angiotensina; BRA: bloqueadores do receptor da angiotensina; OMC: outros medicamentos cardiovasculares; antiagregantes plaquet&#225;rios; ACG: anticoagulantes; IPADPR: inibidores do receptor ADP plaquet&#225;rio.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-105-03-0265-50076-gf01-pt.jpg"/></fig>
        </sec>
        <sec>
          <title>Custo do tratamento farmacol&#243;gico atrav&#233;s de preg&#227;o</title>
          <p>Em pacientes com IC, o custo total foi de $534.010,20 (n = 726), sendo a mediana do custo mensal por paciente de $10,15 (IQ 3,51-40,22). As classes mais caras de medicamentos em valores decrescentes usados para IC foram OMNC, hipolipemiantes e OMC (<xref ref-type="table" rid="t07">Tabela 3</xref>).</p>
          <table-wrap id="t07">
            <label>Tabela 3</label>
            <caption>
              <title>Custo total em d&#243;lares dos medicamentos prescritos para popula&#231;&#245;es de estudo sobre insufici&#234;ncia card&#237;aca e transplante card&#237;aco</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th rowspan="3" align="left">
                    <bold>Medicamento prescrito</bold>
                  </th>
                  <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>IC</bold>
                  </th>
                  <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>TC</bold>
                  </th>
                </tr>
                <tr>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Preg&#227;o</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Preg&#227;o</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Privado</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Privado</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Preg&#227;o</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Preg&#227;o</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Privado</bold>
                  </th>
                  <th align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>Privado</bold>
                  </th>
                </tr>
                <tr>
                  <th align="center">
                    <bold>Total</bold>
                  </th>
                  <th align="center">
                    <bold>%</bold>
                  </th>
                  <th align="center">
                    <bold>Total</bold>
                  </th>
                  <th align="center">
                    <bold>%</bold>
                  </th>
                  <th align="center">
                    <bold>Total</bold>
                  </th>
                  <th align="center">
                    <bold>%</bold>
                  </th>
                  <th align="center">
                    <bold>Total</bold>
                  </th>
                  <th align="center">
                    <bold>%</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Betabloqueador</td>
                  <td align="center">5.587,37</td>
                  <td align="center">1,05</td>
                  <td align="center">594.268,42</td>
                  <td align="center">14,89</td>
                  <td align="center">600,39</td>
                  <td align="center">0,03</td>
                  <td align="center">13.832,19</td>
                  <td align="center">0,24</td>
                </tr>
                <tr>
                  <td align="left">Diur&#233;tico</td>
                  <td align="center">7.656,28</td>
                  <td align="center">1,43</td>
                  <td align="center">146.626,03</td>
                  <td align="center">3,67</td>
                  <td align="center">368,85</td>
                  <td align="center">0,02</td>
                  <td align="center">8.441,09</td>
                  <td align="center">0,15</td>
                </tr>
                <tr>
                  <td align="left">BCC</td>
                  <td align="center">1.212,11</td>
                  <td align="center">0,23</td>
                  <td align="center">58.448,57</td>
                  <td align="center">1,46</td>
                  <td align="center">6.847,05</td>
                  <td align="center">0,38</td>
                  <td align="center">51.373,17</td>
                  <td align="center">0,90</td>
                </tr>
                <tr>
                  <td align="left">IECA, BRA</td>
                  <td align="center">16.905,47</td>
                  <td align="center">3,16</td>
                  <td align="center">209.315,46</td>
                  <td align="center">5,24</td>
                  <td align="center">2.102,12</td>
                  <td align="center">0,12</td>
                  <td align="center">15.675,55</td>
                  <td align="center">0,27</td>
                </tr>
                <tr>
                  <td align="left">OCD</td>
                  <td align="center">24.174,38</td>
                  <td align="center">4,52</td>
                  <td align="center">162.075,63</td>
                  <td align="center">4,06</td>
                  <td align="center">4.846,76</td>
                  <td align="center">0,27</td>
                  <td align="center">15.933,67</td>
                  <td align="center">0,28</td>
                </tr>
                <tr>
                  <td align="left">Hipolipemiante</td>
                  <td align="center">79.108,02</td>
                  <td align="center">14,80</td>
                  <td align="center">196.806,89</td>
                  <td align="center">4,93</td>
                  <td align="center">6.267,88</td>
                  <td align="center">0,35</td>
                  <td align="center">66.905,15</td>
                  <td align="center">1,17</td>
                </tr>
                <tr>
                  <td align="left">Antiagregante plaquet&#225;rio</td>
                  <td align="center">566,45</td>
                  <td align="center">0,11</td>
                  <td align="center">19.825,63</td>
                  <td align="center">0,50</td>
                  <td align="center">67,07</td>
                  <td align="center">0,00</td>
                  <td align="center">2.347,49</td>
                  <td align="center">0,04</td>
                </tr>
                <tr>
                  <td align="left">ACG ou IPADPR</td>
                  <td align="center">7.911,35</td>
                  <td align="center">0,15</td>
                  <td align="center">58.458,19</td>
                  <td align="center">1,46</td>
                  <td align="center">662,50</td>
                  <td align="center">0,04</td>
                  <td align="center">9.667,25</td>
                  <td align="center">0,17</td>
                </tr>
                <tr>
                  <td align="left">Antiarr&#237;tmicos</td>
                  <td align="center">1.993,28</td>
                  <td align="center">0,37</td>
                  <td align="center">17.018,91</td>
                  <td align="center">0,43</td>
                  <td align="center">40,55</td>
                  <td align="center">0,00</td>
                  <td align="center">729,86</td>
                  <td align="center">0,01</td>
                </tr>
                <tr>
                  <td align="left">Digit&#225;lico</td>
                  <td align="center">672,34</td>
                  <td align="center">0,13</td>
                  <td align="center">15.980,01</td>
                  <td align="center">0,40</td>
                  <td align="center">18,70</td>
                  <td align="center">0,00</td>
                  <td align="center">336,58</td>
                  <td align="center">0,01</td>
                </tr>
                <tr>
                  <td align="left">Nitrato</td>
                  <td align="center">5.300,55</td>
                  <td align="center">0,99</td>
                  <td align="center">37.563,87</td>
                  <td align="center">0,94</td>
                  <td align="center">559,03</td>
                  <td align="center">0,03</td>
                  <td align="center">1.799,95</td>
                  <td align="center">0,03</td>
                </tr>
                <tr>
                  <td align="left">Antibi&#243;tico</td>
                  <td align="center">217,40</td>
                  <td align="center">0,04</td>
                  <td align="center">5.880,07</td>
                  <td align="center">0,15</td>
                  <td align="center">6.647,44</td>
                  <td align="center">0,37</td>
                  <td align="center">199.964,37</td>
                  <td align="center">3,49</td>
                </tr>
                <tr>
                  <td align="left">Imunossupressor</td>
                  <td align="center">-</td>
                  <td align="center">-</td>
                  <td align="center">-</td>
                  <td align="center">-</td>
                  <td align="center">1.540.724,53</td>
                  <td align="center">86,20</td>
                  <td align="center">4.159.017,41</td>
                  <td align="center">72,63</td>
                </tr>
                <tr>
                  <td align="left">ONCD</td>
                  <td align="center">390.244,35</td>
                  <td align="center">73,02</td>
                  <td align="center">2.468.908,68</td>
                  <td align="center">61,86</td>
                  <td align="center">217.709,30</td>
                  <td align="center">12,18</td>
                  <td align="center">1.179.687,44</td>
                  <td align="center">20,60</td>
                </tr>
                <tr>
                  <td align="left">TOTAL</td>
                  <td align="center">534.428,49</td>
                  <td align="center">100</td>
                  <td align="center">3.991.176,38</td>
                  <td align="center">100</td>
                  <td align="center">1.787.462,17</td>
                  <td align="center">100</td>
                  <td align="center">5.725.965,20</td>
                  <td align="center">100</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN7">
                <p>HF: insufici&#234;ncia card&#237;aca; HT: transplante card&#237;aco; ACG: anticoagulante; IPADPR: inibidor do receptor adenosina difosfato plaquet&#226;rio; OMNC: outro medicamento n&#227;o cardiovascular; betabloqueador (atenolol, bisoprolol, metoprolol, carvedilol, propranolol, sotalol); diur&#233;tico (furosemida, hidroclorotiazida, clortalidona, espironolactona); BCC: bloqueador do canal de c&#225;lcio (diltiazem, verapamil, anlodipino, nifedipina, losartana); IECA: inibidor da enzima de convers&#227;o da angiotensina (captopril, enalapril, lisinopril); BRA: bloqueador do receptor da angiotensina; hipolipemiante (atorvastatina, ciprofibrato, ezetimiba, rosuvastatina, sinvastatina); antiagregante plaquet&#225;rio (aspirina); ACG ou IPADPR (enoxaparina, varfarina, clopidogrel); antiarr&#237;tmicos (amiodarona, propafenona); digit&#225;lico (digoxina); nitrato (isossorbida, propatilnitrato). OMC: outros medicamentos cardiovasculares (clonidina, doxazosina, hidralazina, metildopa)</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Por outro lado, o custo total para receptores de TC foi de $1.787.462,17 (n = 146), sendo a mediana do custo mensal por paciente de $393,08 (IQ 124,74-774,76). As classes mais caras de medicamentos nesse grupo foram imunossupressores e OMNC (<xref ref-type="table" rid="t07">Tabela 3</xref>).</p>
        </sec>
        <sec>
          <title>Custo do tratamento farmacol&#243;gico no mercado privado</title>
          <p>Em pacientes com IC, o custo total estimado foi de $3.991.176,38 (n = 726), sendo a mediana do custo mensal por paciente de $161,76 (IQ 86,05-340,15). As classes mais caras de medicamentos em ordem decrescente de valor para IC foram OMNC e betabloqueadores (<xref ref-type="table" rid="t07">Tabela 3</xref>).</p>
          <p>O custo total para receptores de TC foi de $5.725.965,20 (n = 146), sendo a mediana do custo mensal por paciente de $1.207,70 (IQ 604,48-2.499,97). As classes mais caras de medicamentos pata TC foram imunossupressores e OMNC (<xref ref-type="table" rid="t07">Tabela 3</xref>).</p>
        </sec>
        <sec>
          <title>Custo do tratamento farmacol&#243;gico atrav&#233;s de preg&#227;o de acordo com an&#225;lises de subgrupo</title>
          <p>A mediana do custo mensal por paciente com IC foi $9,74 (IQ 3,48-33,65, n = 453) para homens e $12,24 (IQ 3,57-44,01, n = 273) para mulheres (p = 0,127). Observou-se um incremento na mediana do custo mensal para IC com hipertens&#227;o (p &lt; 0,001) e diabetes (p &lt; 0,001). Hipertens&#227;o foi respons&#225;vel por aumento de custo de $8,02 (48% maior) (p &lt; 0,001) e diabetes, por aumento de custo de $24,35 (76% maior) (p &lt; 0,001). O custo para miocardiopatia isqu&#234;mica ($16,84, IQ 6,32-16,84) foi significativamente maior do que aquele para doen&#231;a de Chagas ($8,53, IQ 2,98-26,52, p &lt; 0,001) e outras causas ($6,79, IQ 3,21-18,58, p &lt; 0,001). &#233; poss&#237;vel que o custo mais baixo para doen&#231;a de Chagas deva-se ao fato de que pacientes chag&#225;sicos podem n&#227;o tolerar doses completas e de que os m&#233;dicos n&#227;o s&#227;o encorajados a usar doses altas devido &#224; aus&#234;ncia de ensaio cl&#237;nico em doen&#231;a de Chagas. Na an&#225;lise multivariada, indiv&#237;duos mais idosos com IC tiveram custos significativamente mais altos (&#946; = 0,021, p &lt; 0,001), tendo pacientes sem hipertens&#227;o e sem diabetes custos significativamente menores (&#946; = -0,517, p &lt; 0,001; &#946; = -0,979, p &lt; 0,001). A magnitude da redu&#231;&#227;o de custo por preg&#227;o foi maior em diabetes e hipertens&#227;o (<xref ref-type="fig" rid="f04">Figura 2</xref>).</p>
          <fig id="f04">
            <label>Figura 2</label>
            <caption>
              <title>Custo dos medicamentos prescritos dispensados comprados por preg&#227;o em compara&#231;&#227;o aos de farm&#225;cia comercial (FC) de acordo com o diagn&#243;stico de hipertens&#227;o arterial sist&#234;mica e diabetes mellitus em insufici&#234;ncia card&#237;aca e transplante card&#237;aco.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-105-03-0265-50076-gf02-pt.jpg"/></fig>
          <p>No grupo TC, a mediana do custo mensal por paciente foi $365,17 (IQ 100,83-683,59, n = 101) para homens e $435,58 (IQ 248,40-920,86, n = 45) para mulheres (p = 0,268). Nenhuma comorbidade causou aumento de custo. Observou-se diferen&#231;a estatisticamente significativa entre os custos de pacientes com hist&#243;ria pr&#233;via de miocardiopatia chag&#225;sica ($271,71, IQ 66,49-568,54) e de outras causas ($472,40, IQ 182,05-888,53, p = 0,009). A <xref ref-type="table" rid="t08">Tabela 4</xref>apresenta outras compara&#231;&#245;es entre as vari&#225;veis cl&#237;nicas e a mediana de custo para os dois grupos. Na an&#225;lise multivariada, pacientes de TC sem hipertens&#227;o apresentaram menor custo (&#946; = -0,324, p &lt; 0,001). Nesse modelo, outras vari&#225;veis n&#227;o apresentaram significado estat&#237;stico para prever custo. A magnitude da redu&#231;&#227;o de custo atrav&#233;s preg&#227;o foi maior na presen&#231;a de diabetes e de hipertens&#227;o (<xref ref-type="fig" rid="f04">Figura 2</xref>).</p>
          <table-wrap id="t08">
            <label>Tabela 4</label>
            <caption>
              <title>Custo mensal por preg&#227;o ou mercado privado de medicamentos prescritos para popula&#231;&#245;es de estudo em insufici&#234;ncia card&#237;aca e transplante card&#237;aco de acordo com vari&#225;veis cl&#237;nicas e demogr&#225;ficas</title>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <th rowspan="2" align="left">
                    <bold>CARACTER&#205;STICAS</bold>
                  </th>
                  <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>IC</bold>
                  </th>
                  <th colspan="4" align="center" style="border-bottom-style:solid; border-bottom-width:thin">
                    <bold>TC</bold>
                  </th>
                </tr>
                <tr>
                  <th align="center">
                    <bold>n</bold>
                  </th>
                  <th align="center">
                    <bold>MEDIANA DO CUSTO</bold>
                  </th>
                  <th align="center">
                    <bold>IQ 25%-75%</bold>
                  </th>
                  <th align="center">
                    <bold>p</bold>
                  </th>
                  <th align="center">
                    <bold>n</bold>
                  </th>
                  <th align="center">
                    <bold>MEDIANA DO CUSTO</bold>
                  </th>
                  <th align="center">
                    <bold>IQ 25%-75%</bold>
                  </th>
                  <th align="center">
                    <bold>p</bold>
                  </th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">
                    <bold>Custo do preg&#227;o em $</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Idade, anos</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&lt; 0,001</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,19</td>
                </tr>
                <tr>
                  <td align="left">&#8804; 19</td>
                  <td align="center">5</td>
                  <td align="center">3,16</td>
                  <td align="center">2,87-24,39</td>
                  <td align="center">&#160;</td>
                  <td align="center">9</td>
                  <td align="center">732,48</td>
                  <td align="center">493,62-1.026,12</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">20 - 40</td>
                  <td align="center">68</td>
                  <td align="center">4,35</td>
                  <td align="center">2,07-15,63</td>
                  <td align="center">&#160;</td>
                  <td align="center">37</td>
                  <td align="center">410,07</td>
                  <td align="center">239,07-844,68</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">41 - 65</td>
                  <td align="center">380</td>
                  <td align="center">9,8</td>
                  <td align="center">3,20-45,88</td>
                  <td align="center">&#160;</td>
                  <td align="center">57</td>
                  <td align="center">365,19</td>
                  <td align="center">97,16-619,52</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">&#8805; 65</td>
                  <td align="center">273</td>
                  <td align="center">13,46</td>
                  <td align="center">4,80-52,75</td>
                  <td align="center">&#160;</td>
                  <td align="center">43</td>
                  <td align="center">245,93</td>
                  <td align="center">90,60-1.021,26</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Causas</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&lt; 0,001</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,036</td>
                </tr>
                <tr>
                  <td align="left">Isqu&#233;mica</td>
                  <td align="center">132</td>
                  <td align="center">16,84</td>
                  <td align="center">6,32-16,84</td>
                  <td align="center">&#160;</td>
                  <td align="center">18</td>
                  <td align="center">402,49</td>
                  <td align="center">77,07-932,54</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Chag&#225;sica</td>
                  <td align="center">76</td>
                  <td align="center">8,53</td>
                  <td align="center">2,98-26,52</td>
                  <td align="center">&#160;</td>
                  <td align="center">48</td>
                  <td align="center">271,71</td>
                  <td align="center">66,49-568,54</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Outras</td>
                  <td align="center">217</td>
                  <td align="center">6,79</td>
                  <td align="center">3,21-18,58</td>
                  <td align="center">&#160;</td>
                  <td align="center">73</td>
                  <td align="center">472,40</td>
                  <td align="center">182,05-888,53</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Consulta ambulatorial (n&#250;mero)</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,005</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,016</td>
                </tr>
                <tr>
                  <td align="left">&lt; 5</td>
                  <td align="center">192</td>
                  <td align="center">10,84</td>
                  <td align="center">2,88-39,19</td>
                  <td align="center">&#160;</td>
                  <td align="center">16</td>
                  <td align="center">576,34</td>
                  <td align="center">292,84-1.396,98</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">6 - 10</td>
                  <td align="center">286</td>
                  <td align="center">8,09</td>
                  <td align="center">3,07-30,27</td>
                  <td align="center">&#160;</td>
                  <td align="center">16</td>
                  <td align="center">512,22</td>
                  <td align="center">149,78-1.062,56</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">11 - 15</td>
                  <td align="center">124</td>
                  <td align="center">15,13</td>
                  <td align="center">5,23-70,22</td>
                  <td align="center">&#160;</td>
                  <td align="center">42</td>
                  <td align="center">227,05</td>
                  <td align="center">73,86-607,01</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">16 - 20</td>
                  <td align="center">46</td>
                  <td align="center">6,55</td>
                  <td align="center">2,91-54,35</td>
                  <td align="center">&#160;</td>
                  <td align="center">28</td>
                  <td align="center">273,05</td>
                  <td align="center">61,67-654,69</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">&#8805; 21</td>
                  <td align="center">78</td>
                  <td align="center">12,89</td>
                  <td align="center">5,06-41,86</td>
                  <td align="center">&#160;</td>
                  <td align="center">44</td>
                  <td align="center">493,46</td>
                  <td align="center">223,14-847,01</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Classe funcional</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&lt; 0,001</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">I e II</td>
                  <td align="center">326</td>
                  <td align="center">7,04</td>
                  <td align="center">2,82-32,86</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">III e IV</td>
                  <td align="center">101</td>
                  <td align="center">16,47</td>
                  <td align="center">5,43-67,55</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Etnia</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,96</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,34</td>
                </tr>
                <tr>
                  <td align="left">Branca e amarela</td>
                  <td align="center">564</td>
                  <td align="center">10,07</td>
                  <td align="center">3,59-10,07</td>
                  <td align="center">&#160;</td>
                  <td align="center">126</td>
                  <td align="center">390,47</td>
                  <td align="center">118,43-737,32</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Negra e parada</td>
                  <td align="center">148</td>
                  <td align="center">10,92</td>
                  <td align="center">3,52-40,47</td>
                  <td align="center">&#160;</td>
                  <td align="center">20</td>
                  <td align="center">40,47</td>
                  <td align="center">225,65-1.074,95</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>FEVE</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,43</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,97</td>
                </tr>
                <tr>
                  <td align="left">&#8804; 40%</td>
                  <td align="center">296</td>
                  <td align="center">11,82</td>
                  <td align="center">3,47-47,80</td>
                  <td align="center">&#160;</td>
                  <td align="center">10</td>
                  <td align="center">358,93</td>
                  <td align="center">86,11-957,32</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">&gt; 40%</td>
                  <td align="center">119</td>
                  <td align="center">9,46</td>
                  <td align="center">3,72-27,61</td>
                  <td align="center">&#160;</td>
                  <td align="center">126</td>
                  <td align="center">390,47</td>
                  <td align="center">124,75-740,92</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Custo privado em $</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Idade, anos</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&lt; 0,001</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,52</td>
                </tr>
                <tr>
                  <td align="left">&#8804; 19</td>
                  <td align="center">5</td>
                  <td align="center">105,45</td>
                  <td align="center">52,69-520,48</td>
                  <td align="center">&#160;</td>
                  <td align="center">09</td>
                  <td align="center">1.851,58</td>
                  <td align="center">1.284,76-2.755,11</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">20 - 40</td>
                  <td align="center">68</td>
                  <td align="center">114,52</td>
                  <td align="center">62,57-188,12</td>
                  <td align="center">&#160;</td>
                  <td align="center">37</td>
                  <td align="center">1.234,25</td>
                  <td align="center">839,74-2.455,04</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">41 - 65</td>
                  <td align="center">380</td>
                  <td align="center">148,90</td>
                  <td align="center">79,68-331,97</td>
                  <td align="center">&#160;</td>
                  <td align="center">57</td>
                  <td align="center">1.155,17</td>
                  <td align="center">556,26-2.491,22</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">&#8805; 65</td>
                  <td align="center">273</td>
                  <td align="center">193,19</td>
                  <td align="center">113,57-420,72</td>
                  <td align="center">&#160;</td>
                  <td align="center">43</td>
                  <td align="center">1.004,99</td>
                  <td align="center">572,62-2.734,57</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Causas</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,004</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,14</td>
                </tr>
                <tr>
                  <td align="left">Isqu&#233;mica</td>
                  <td align="center">132</td>
                  <td align="center">200,96</td>
                  <td align="center">113,73-447,87</td>
                  <td align="center">&#160;</td>
                  <td align="center">18</td>
                  <td align="center">1.581,77</td>
                  <td align="center">554,10-3.141,53</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Chag&#225;sica</td>
                  <td align="center">76</td>
                  <td align="center">138,85</td>
                  <td align="center">19,03-303,53</td>
                  <td align="center">&#160;</td>
                  <td align="center">48</td>
                  <td align="center">1.024,00</td>
                  <td align="center">355,21-1.553,49</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Outras</td>
                  <td align="center">217</td>
                  <td align="center">139,82</td>
                  <td align="center">84,39-274,33</td>
                  <td align="center">&#160;</td>
                  <td align="center">73</td>
                  <td align="center">1.378,35</td>
                  <td align="center">784,73-2.485,21</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Consulta ambulatorial (n&#250;mero)</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,002</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,009</td>
                </tr>
                <tr>
                  <td align="left">&lt; 5</td>
                  <td align="center">192</td>
                  <td align="center">168,48</td>
                  <td align="center">67,85-321,16</td>
                  <td align="center">&#160;</td>
                  <td align="center">16</td>
                  <td align="center">1.507,97</td>
                  <td align="center">984,70-3.821,39</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">6 - 10</td>
                  <td align="center">286</td>
                  <td align="center">147,90</td>
                  <td align="center">79,49-308,74</td>
                  <td align="center">&#160;</td>
                  <td align="center">16</td>
                  <td align="center">1.530,34</td>
                  <td align="center">713,99-2.890,81</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">11 - 15</td>
                  <td align="center">124</td>
                  <td align="center">190,69</td>
                  <td align="center">111,44-510,07</td>
                  <td align="center">&#160;</td>
                  <td align="center">42</td>
                  <td align="center">800,50</td>
                  <td align="center">446,29-2.232,58</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">16 - 20</td>
                  <td align="center">46</td>
                  <td align="center">151,78</td>
                  <td align="center">89,09-339,14</td>
                  <td align="center">&#160;</td>
                  <td align="center">28</td>
                  <td align="center">905,63</td>
                  <td align="center">309,77-1.756,99</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">&#8805; 21</td>
                  <td align="center">78</td>
                  <td align="center">189,04</td>
                  <td align="center">116,25-363,56</td>
                  <td align="center">&#160;</td>
                  <td align="center">44</td>
                  <td align="center">1.445,44</td>
                  <td align="center">955,98-2.737,73</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Classe funcional</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,010</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">I e II</td>
                  <td align="center">326</td>
                  <td align="center">134,27</td>
                  <td align="center">72,15-278,23</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">III e IV</td>
                  <td align="center">101</td>
                  <td align="center">213,35</td>
                  <td align="center">110,97-637,56</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Etnia</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,57</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,15</td>
                </tr>
                <tr>
                  <td align="left">Branca e amarela</td>
                  <td align="center">564</td>
                  <td align="center">169,05</td>
                  <td align="center">85,18-339,40</td>
                  <td align="center">&#160;</td>
                  <td align="center">126</td>
                  <td align="center">1.161,89</td>
                  <td align="center">573,85-2.432,95</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">Negra e parda</td>
                  <td align="center">148</td>
                  <td align="center">157,10</td>
                  <td align="center">86,02-391,50</td>
                  <td align="center">&#160;</td>
                  <td align="center">20</td>
                  <td align="center">1.709,93</td>
                  <td align="center">800,58-3.134,78</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>FEVE</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,92</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">0,32</td>
                </tr>
                <tr>
                  <td align="left">&#8804; 40%</td>
                  <td align="center">310</td>
                  <td align="center">149,32</td>
                  <td align="center">75,75-331,42</td>
                  <td align="center">&#160;</td>
                  <td align="center">10</td>
                  <td align="center">1.133,99</td>
                  <td align="center">712,47-2.548,44</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">&gt; 40%</td>
                  <td align="center">129</td>
                  <td align="center">136,30</td>
                  <td align="center">72,65-286,64</td>
                  <td align="center">&#160;</td>
                  <td align="center">126</td>
                  <td align="center">1.203,64</td>
                  <td align="center">583,40-2.487,27</td>
                  <td align="center">&#160;</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN8">
                <p>Medidas apresentadas como mediana e intervalo interquartil. FEVE: fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda; IC: insufici&#234;ncia card&#237;aca; TC: transplante card&#237;aco.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Custo do tratamento farmacol&#243;gico na farm&#225;cia comercial de acordo com an&#225;lises de subgrupo</title>
          <p>No grupo IC, a mediana de custo mensal para homens foi $155,34 (IQ 91,30-314,85) e para mulheres foi $175,21 (IQ 80,68-415,44) (p = 0,412). Com rela&#231;&#227;o a comorbidades, houve um aumento na mediana de custo mensal associado a hipertens&#227;o (p &lt; 0,001) e diabetes (p &lt; 0,001). Hipertens&#227;o foi respons&#225;vel por incremento de custo de $60,35 (28% maior) (p = 0,005), e diabetes, por incremento de custo de $130,19 (48% maior) (p &lt; 0,001). O custo da miocardiopatia isqu&#234;mica ($200,96, IQ 113,73-447,87) foi significativamente maior do que o da miocardiopatia chag&#225;sica ($138,85, IQ 19,03-303,53, p = 0,003) o de outras causas ($139,82, IQ 84,39-274,33, p = 0,004). Na an&#225;lise multivariada, observou-se uma significativa intera&#231;&#227;o entre custo e idade para pacientes com IC, tendo indiv&#237;duos mais idosos apresentado custos significativamente maiores (&#946; = 0,018, p &lt; 0,001). Homens (&#946; = -0,165, p &lt; 0,001) e indiv&#237;duos n&#227;o diab&#233;ticos apresentaram custos significativamente menores (&#946; = 0,568, p = 0,003).</p>
          <p>No grupo TC, a mediana de custo mensal dos medicamentos prescritos apresentou tend&#234;ncia a ser menor para homens ($1.056,83, IQ 532,31-2.325,00) do que para mulheres ($1.313,48, IQ 907,33-3.011,20) (p = 0,069). No entanto, diabetes foi a &#250;nica comorbidade respons&#225;vel por aumento de custo ($795,99, 40% maior) (p = 0,045). N&#227;o houve diferen&#231;a de custo entre as causas. A <xref ref-type="table" rid="t08">Tabela 4</xref> apresenta compara&#231;&#245;es adicionais entre as vari&#225;veis cl&#237;nicas e a mediana do custo mensal para os dois grupos. No grupo TC, a an&#225;lise multivariada mostrou significativa intera&#231;&#227;o entre custo e aus&#234;ncia de hipertens&#227;o (&#946; = -0,218, p &lt; 0,001). A aus&#234;ncia de hipertens&#227;o resultou em menores custos no sistema privado. Nesse modelo, n&#227;o houve diferen&#231;as estatisticamente significativas para outras vari&#225;veis.</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>At&#233; onde sabemos, este &#233; o primeiro estudo a demonstrar que o custo da dispensa&#231;&#227;o de medicamentos prescritos para pacientes com IC e TC, comprados atrav&#233;s de preg&#227;o, &#233; substancialmente inferior ao estimado no mercado privado para a pr&#225;tica cl&#237;nica. Nessa compara&#231;&#227;o, a compra atrav&#233;s de preg&#227;o para IC seguida por dispensa&#231;&#227;o aos pacientes chega a ser uma barganha. A idade mais avan&#231;ada associou-se a custos mais altos, e a aus&#234;ncia de diabetes, a custos mais baixos em pacientes com IC nos dois sistemas de compra. A magnitude da redu&#231;&#227;o de custo atrav&#233;s do preg&#227;o foi maior na presen&#231;a de diabetes e de hipertens&#227;o (<xref ref-type="fig" rid="f04">Figura 2</xref>).</p>
        <p>Nosso custo para o tratamento farmacol&#243;gico da IC foi significativamente menor quando comparado ao relatado previamente, variando de $261 a $438 por m&#234;s por paciente<xref ref-type="bibr" rid="B09">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>. O custo dos medicamentos comprados no preg&#227;o no nosso estudo variou de 2,28% a 3,8% daqueles publicados nos EUA, enquanto o estimado no mercado privado variou de 37% a 62%. O sistema de sa&#250;de dos EUA, conhecido como um dos mais dispendiosos no mundo e com maiores pre&#231;os para os medicamentos<xref ref-type="bibr" rid="B15">15</xref>, pode ter contribu&#237;do para tais diferen&#231;as. Entretanto, a enorme diferen&#231;a de custo corroborou nossos achados da efici&#234;ncia do preg&#227;o em reduzir custos do tratamento de IC.</p>
        <p>Com rela&#231;&#227;o ao TC, a compara&#231;&#227;o com os dados de apenas um estudo publicado analisando o custo de imunossupressores at&#233; dois anos ap&#243;s transplante de &#243;rg&#227;os s&#243;lidos mostrou que o preg&#227;o pode ser proporcionalmente menos eficiente em reduzir custos ap&#243;s TC. Naquele estudo, os custos variaram de $448 a $1.321 por paciente por m&#234;s<xref ref-type="bibr" rid="B16">16</xref>. Entretanto, o custo dos outros medicamentos n&#227;o foi considerado, o que poderia subestimar o custo total do tratamento farmacol&#243;gico.</p>
        <p>Para explicar nossos resultados, especulamos que a compra por preg&#227;o possa criar um ambiente competitivo para muitas ind&#250;strias envolvidas na produ&#231;&#227;o de medicamentos para IC. A concorr&#234;ncia, ao inv&#233;s de ser uma desvantagem para a ind&#250;stria, serviria para impulsionar os fabricantes de medicamentos a melhorar seus processos de neg&#243;cio para manter o lucro ao mesmo tempo em que beneficiaria a sociedade. Ao contr&#225;rio, o pequeno n&#250;mero de ind&#250;strias envolvidas na produ&#231;&#227;o dos imunossupressores e o restrito mercado podem impedir o desenvolvimento de um ambiente competitivo e limitar a efici&#234;ncia do preg&#227;o para TC. Como resultado, a terapia farmacol&#243;gica no transplante tem alto custo se comparada &#224;quela da IC<xref ref-type="bibr" rid="B16">16</xref>.</p>
        <p>Como esperado e confirmando dados publicados, as comorbidades associaram-se com maior custo<xref ref-type="bibr" rid="B08">8</xref><sup>,</sup><xref ref-type="bibr" rid="B09">9</xref>. O maior custo para pacientes mais idosos poderia ser explicado pelo fato de que o envelhecimento leva a um maior n&#250;mero de comorbidades. Em geral, as comorbidades requerem tratamento com polifarm&#225;cia; entretanto, &#233; importante ressaltar que diabetes se associou a maior aumento de custos na IC, provavelmente como consequ&#234;ncia do papel da diabetes no desenvolvimento de muitas comorbidades<xref ref-type="bibr" rid="B09">9</xref>. O preg&#227;o, no entanto, foi mais eficiente na diabetes (<xref ref-type="fig" rid="f04">Figura 2</xref>).</p>
        <sec>
          <title>Implica&#231;&#245;es cl&#237;nicas e no sistema de sa&#250;de</title>
          <p>Nossos achados sugerem que o preg&#227;o seja uma alternativa positiva de apoio financeiro ao sistema de sa&#250;de e poderia ser introduzido em sistema de sa&#250;de de outros pa&#237;ses para reduzir o custo do tratamento farmacol&#243;gico da IC e ap&#243;s TC. Os envolvidos em suprimento de medicamentos para IC deveriam considerar a possibilidade de compra por preg&#227;o e dispensa&#231;&#227;o para os pacientes. O custo dos medicamentos para pacientes n&#227;o hospitalizados pode influenciar sua ades&#227;o ao tratamento farmacol&#243;gico recomendado<xref ref-type="bibr" rid="B10">10</xref>. O menor custo poderia resultar em maior acesso a esse tratamento com maior ades&#227;o aos medicamentos prescritos, melhor sobrevida e menos hospitaliza&#231;&#227;o. O uso do preg&#227;o mundo afora para pol&#237;ticas de sa&#250;de poderia beneficiar muitos indiv&#237;duos em pa&#237;ses desenvolvidos e principalmente n&#227;o desenvolvidos, reduzindo o custo da IC.</p>
        </sec>
        <sec>
          <title>Limita&#231;&#245;es</title>
          <p>Nosso estudo tem limita&#231;&#245;es. Avaliamos apenas medicamentos prescritos e dispensados; consequentemente, n&#227;o pudemos verificar a ades&#227;o do paciente ao tratamento. No entanto, &#233; suficiente para demonstrar quanto de terapia farmacol&#243;gica ocorre na pr&#225;tica cl&#237;nica. Os regimes administrados foram baseados naqueles prescritos por cardiologistas especializados em um centro terci&#225;rio, podendo n&#227;o representar assist&#234;ncia prim&#225;ria em IC. Nosso estudo unic&#234;ntrico n&#227;o incluiu pacientes de m&#250;ltiplas pr&#225;ticas nem de diferentes regi&#245;es geogr&#225;ficas brasileiras; entretanto, em geral, nessas condi&#231;&#245;es o tratamento farmacol&#243;gico n&#227;o &#233; orientado por diretrizes. Por fim, nosso estudo foi uma revis&#227;o retrospectiva de registros m&#233;dicos, uma vez que um estudo prospectivo demandaria mais tempo e recursos econ&#244;micos.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>O presente estudo sobre pr&#225;tica contempor&#226;nea demonstrou que o preg&#227;o pode ser importante para reduzir o custo da terapia farmacol&#243;gica em IC para pacientes ambulatoriais ou ap&#243;s TC. Al&#233;m disso, comorbidades e idade avan&#231;ada associaram-se a maior custo, o que deve ser considerado quando do planejamento de estrat&#233;gias de sa&#250;de para IC. Da mesma forma, o principal achado &#233; que o preg&#227;o possa tornar-se estrat&#233;gia governamental para expandir o acesso dos menos privilegiados &#224; terapia medicamentosa e no melhor uso dos recursos p&#250;blicos.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
