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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</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 - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">D5dnnrCsQ9mND6vZkmQZYww</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018001300029</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180104</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Economic Burden of Heart Conditions in Brazil</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Stevens</surname>
            <given-names>Bryce</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pezzullo</surname>
            <given-names>Lynne</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Verdian</surname>
            <given-names>Lara</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tomlinson</surname>
            <given-names>Josh</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>George</surname>
            <given-names>Alice</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bacal</surname>
            <given-names>Fernando</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Deloitte Access Economics Pty Ltd</institution>
        <country country="AU">Austr&#225;lia</country>
        <institution content-type="original">Deloitte Access Economics Pty Ltd, Austr&#225;lia</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <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>
          <city>S&#227;o Paulo</city>
          <state>SP</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - HC-Faculdade de Medicina da USP, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Alice George</bold>, 8 Brindabella Circuit, 2609, Canberra Airport, Canberra &#8211; Australia. E-mail: <email>algeorge@deloitte.com.au</email>, <email>brstevens@deloitte.com.au</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Stevens B, Pezzullo L, Verdian L; Acquisition of data: Stevens B, Tomlinson J; Analysis and interpretation of the data: Stevens B, Pezzullo L, Verdian L, Tomlinson J; Statistical analysis: Stevens B, Tomlinson J; Obtaining financing: Pezzullo L; Writing of the manuscript: Stevens B, Verdian L, Tomlinson J, George A; Critical revision of the manuscript for intellectual content: Stevens B, Pezzullo L, Bacal F.</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-ppub">
        <month>7</month>
        <year>2018</year>
      </pub-date>
      <volume>111</volume>
      <issue>1</issue>
      <fpage>29</fpage>
      <lpage>36</lpage>
      <history>
        <date date-type="received">
          <day>02</day>
          <month>02</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>14</day>
          <month>07</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>31</day>
          <month>07</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Heart conditions impose physical, social, financial and health-related quality of life limitations on individuals in Brazil.</p>
        </sec>
        <sec>
          <title>Objectives:</title>
          <p>This study assessed the economic burden of four main heart conditions in Brazil: hypertension, heart failure, myocardial infarction, and atrial fibrillation. In addition, the cost-effectiveness of telemedicine and structured telephone support for the management of heart failure was assessed.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>A standard cost of illness framework was used to assess the costs associated with the four conditions in 2015. The analysis assessed the prevalence of the four conditions and, in the case of myocardial infarction, also its incidence. It further assessed the conditions&#8217; associated expenditures on healthcare treatment, productivity losses from reduced employment, costs of providing formal and informal care, and lost <underline>wellbeing.</underline> The analysis was informed by a targeted literature review, data scan and modelling. All inputs and methods were validated by consulting 15 clinicians and other stakeholders in Brazil. The cost-effectiveness analysis was based on a meta-analysis and economic evaluation of post-discharge programs in patients with heart failure, assessed from the perspective of the Brazilian Unified Healthcare System (Sistema Unico de Saude).</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Myocardial infarction imposes the greatest financial cost (22.4 billion reais/6.9 billion USD), followed by heart failure (22.1 billion reais/6.8 billion USD), hypertension (8 billion reais/2.5 billion USD) and, finally, atrial fibrillation (3.9 billion reais/1.2 billion USD). Telemedicine and structured telephone support are cost-effective interventions for achieving improvements in the management of heart failure.</p>
        </sec>
        <sec>
          <title>Conclusions:</title>
          <p>Heart conditions impose substantial loss of wellbeing and financial costs in Brazil and should be a public health priority.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Cardiovascular Diseases/economics</kwd>
        <kwd>Hypertension</kwd>
        <kwd>Heart Failure</kwd>
        <kwd>Myocardial Infarction</kwd>
        <kwd>Atrial Fibrillation</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Heart conditions impose physical, social, financial and health-related quality of life limitations on individuals. These conditions result in an economic burden and impact on society due to expenditures on healthcare treatment, productivity losses from employment impacts, costs of providing formal and informal care, and lost wellbeing. Circulatory diseases presently represent the biggest health burden worldwide, accounting for over 17 million deaths every year; this represents half of all noncommunicable disease deaths.<xref ref-type="bibr" rid="B1">1</xref>
			</p>
      <p>At the 2016 World Congress of Cardiology &amp; Cardiovascular Health, the Mexico Declaration for Circulatory Health was signed by leading global organisations committed to improving circulatory health and reducing deaths and disability from heart diseases and stroke around the world. This is aligned with a clear target, set by the World Health Organization (WHO) and signed by country signatories, of reducing deaths from noncommunicable disease by 25 per cent by 2025.<xref ref-type="bibr" rid="B1">1</xref> Our analysis identifies the current burden heart conditions have on Brazil and consequently the potential economic benefits that could result from addressing it.</p>
      <p>This study aims to assess the economic (health system and productivity) impact of four heart conditions in Brazil, providing estimates of the annual cost for the year 2015: hypertension (HTN), myocardial infarction (MI), atrial fibrillation (AF) and heart failure (HF). This study also analyzes the cost-effectiveness of two interventions for HF: telemedicine (TM) and structured telephone support (STS).</p>
    </sec>
    <sec sec-type="methods">
      <title>Method</title>
      <p>This research is part of a larger study of the Latin American region, with country-specific results also identified for Mexico, Chile, Peru, Venezuela, Colombia, Ecuador, Panama and El Salvador. These results for Brazil were presented at ISPOR Vienna (November 2016) and the World Cardiovascular Congress (June 2016).</p>
      <sec>
        <title>Cost of illness</title>
        <p>The analysis was based on estimating the prevalence, incidence, loss of wellbeing, health system and productivity losses attributed to the four heart conditions. Total cost estimates were adjusted based on the comorbidity between conditions. Underpinning the study was a literature search that used search terms associated with the country, region, epidemiology and economic impact of the four heart conditions. Sources included PubMed, government, healthcare and patient organization websites, and general internet search engines.</p>
      </sec>
      <sec>
        <title>Prevalence/incidence of conditions</title>
        <p>The sources used for estimating the prevalence or incidence are outlined in <xref ref-type="table" rid="t1">Table 1</xref>. Whenever possible, Brazil specific rates were used. All estimates were checked with stakeholders interviewed for the project. Identified rates were applied to projections from the United Nations World Population Prospects.<xref ref-type="bibr" rid="B2">2</xref>
				</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Number of people with the four heart conditions in Brazil, 2015</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="33%"/>
              <col width="33%"/>
              <col width="33%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Condition</th>
                <th align="center">Number of people</th>
                <th align="center">Percentage of the adult population<xref ref-type="table-fn" rid="TFN1">*</xref>
								</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">HF</td>
                <td align="center">2 845 722</td>
                <td align="center">2.0</td>
              </tr>
              <tr>
                <td align="left">MI</td>
                <td align="center">334 978</td>
                <td align="center">0.2</td>
              </tr>
              <tr>
                <td align="left">AF</td>
                <td align="center">1 202 151</td>
                <td align="center">0.8</td>
              </tr>
              <tr>
                <td align="left">HTN</td>
                <td align="center">44 526 201</td>
                <td align="center">31.2</td>
              </tr>
              <tr>
                <td align="left">Total conditions</td>
                <td align="center">48 909 052</td>
                <td align="center">34.3</td>
              </tr>
              <tr>
                <td align="left">Total persons with any condition (i.e. accounting for comorbidities)</td>
                <td align="center">45 658 048</td>
                <td align="center">32.0</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <label>*</label>
              <p>Percentage reflects the evidence from studies among populations aged 20 years and over. HF: heart failure; MI: myocardial infarction; AF: atrial fibrillation; HTN: hypertension.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Loss of wellbeing</title>
        <p>Disability weights were based on the WHO Global Burden of Disease studies<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> as shown in <xref ref-type="table" rid="t2">Table 2</xref>. These were then multiplied by the prevalence estimates to identify the years lost to disability for 2015. Years lost to life were based on reported mortality for each condition.</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Financial cost of heart conditions in Brazil, 2015 (millions of reais)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
              <col width="14%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Category</th>
                <th align="center">HF</th>
                <th align="center">MI</th>
                <th align="center">AF</th>
                <th align="center">HTN</th>
                <th align="center">Total (unadjusted)</th>
                <th align="center">Total (adjusted for comorbidities)<sup><xref ref-type="table-fn" rid="TFN5">^</xref></sup></th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="2">Health system costs</td>
                <td align="center">14 469</td>
                <td align="center">16 119</td>
                <td align="center">3 697</td>
                <td align="center">1 098</td>
                <td align="center">35 382</td>
                <td align="center">35 382</td>
              </tr>
              <tr>
                <td align="center">65%</td>
                <td align="center">72%</td>
                <td align="center">94%</td>
                <td align="center">14%</td>
                <td align="center">63%</td>
                <td align="center">63%</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Productivity losses</td>
                <td align="center">7 663</td>
                <td align="center">6 257</td>
                <td align="center">225</td>
                <td align="center">6 927</td>
                <td align="center">21 071</td>
                <td align="center">20 858</td>
              </tr>
              <tr>
                <td align="center">35%</td>
                <td align="center">28%</td>
                <td align="center">6%</td>
                <td align="center">86%</td>
                <td align="center">37%</td>
                <td align="center">37%</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Income forgone by individuals<xref ref-type="table-fn" rid="TFN3">*</xref>
								</td>
                <td align="center">3 528</td>
                <td align="center">4 540</td>
                <td align="center">156</td>
                <td align="center">2 063</td>
                <td align="center">10 287</td>
                <td align="center">10 196</td>
              </tr>
              <tr>
                <td align="center">16%</td>
                <td align="center">20%</td>
                <td align="center">4%</td>
                <td align="center">26%</td>
                <td align="center">18%</td>
                <td align="center">18%</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Income forgone by businesses<xref ref-type="table-fn" rid="TFN3">*</xref>
								</td>
                <td align="center">333</td>
                <td align="center">403</td>
                <td align="center">31</td>
                <td align="center">4 378</td>
                <td align="center">5 145</td>
                <td align="center">5 050</td>
              </tr>
              <tr>
                <td align="center">2%</td>
                <td align="center">2%</td>
                <td align="center">1%</td>
                <td align="center">55%</td>
                <td align="center">9%</td>
                <td align="center">9%</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Opportunity cost of informal care by family/friends</td>
                <td align="center">2 404</td>
                <td align="center">196</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">2 600</td>
                <td align="center">2 596</td>
              </tr>
              <tr>
                <td align="center">11%</td>
                <td align="center">1%</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">5%</td>
                <td align="center">5%</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Tax revenue forgone by government<xref ref-type="table-fn" rid="TFN4">**</xref>
								</td>
                <td align="center">1 399</td>
                <td align="center">1 117</td>
                <td align="center">37</td>
                <td align="center">486</td>
                <td align="center">3 039</td>
                <td align="center">3 016</td>
              </tr>
              <tr>
                <td align="center">6%</td>
                <td align="center">5%</td>
                <td align="center">1%</td>
                <td align="center">6%</td>
                <td align="center">5%</td>
                <td align="center">5%</td>
              </tr>
              <tr>
                <td align="left">Total cost</td>
                <td align="center">22 132</td>
                <td align="center">22 375</td>
                <td align="center">3 921</td>
                <td align="center">8 025</td>
                <td align="center">56 454</td>
                <td align="center">56 241</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>Results in millions of reais.</p>
            </fn>
            <fn id="TFN3">
              <label>*</label>
              <p>The result from absenteeism, reduced employment participation, and premature mortality.</p>
            </fn>
            <fn id="TFN4">
              <label>**</label>
              <p>Due to reduced income of individuals with heart conditions and their carers.</p>
            </fn>
            <fn id="TFN5">
              <label>^</label>
              <p>Comorbidity totals do not sum to the total of the individual conditions as one person can have more than one condition and the interaction between conditions causes the total estimate of the four conditions together to vary. HF: heart failure; MI: myocardial infarction; AF: atrial fibrillation; HTN: hypertension.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Health system costs</title>
        <p>The discharges and average length of stay for each of the conditions<xref ref-type="bibr" rid="B5">5</xref> were combined with cost estimates for each of the four condition categories<xref ref-type="bibr" rid="B5">5</xref> to estimate each condition&#8217;s burden on the health system as a share of all conditions treated. This was then combined with an estimate of total relevant health expenditure for Brazil<xref ref-type="bibr" rid="B6">6</xref> to result in the cost of treating each of the four conditions. Health costs were estimated from the perspective of health care payers, i.e. both public and private payers. Cost breakdowns were based on those reported for Brazil.<xref ref-type="bibr" rid="B7">7</xref> This method allows us to reflect most appropriately the impacts based on the number, length of stay and cost intensity of each condition for Brazil specifically. However, data on condition-specific health expenditures are not available for other components of the health system (e.g. primary care). Accordingly, each condition&#8217;s share of total health system expenditure was assumed to be the same as its share of total hospital expenditure.</p>
      </sec>
      <sec>
        <title>Productivity losses</title>
        <p>Consistent with the &#8216;full or near-full employment&#8217; criterion,<sup>a</sup> a human capital approach to the estimation of productivity losses was adopted. Calculations involving productivity losses were based on employment rates by age-gender groups. It was assumed that those with heart conditions were, in the absence of the condition, as likely to be employed as others in their corresponding age-gender group. Forgone wage income was based on wage data for Brazil.<xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>Absenteeism was associated with all of the conditions. For HF it was estimated as 12.66 days for those with NYHA III/IV and 3.04 days per year for those with NYHA I/II.<xref ref-type="bibr" rid="B8">8</xref> Absenteeism was estimated as 3.03 days per year<xref ref-type="bibr" rid="B8">8</xref> for HTN, 75 days per year for those admitted to hospital<xref ref-type="bibr" rid="B9">9</xref> with MI, and 2.1 days per year<xref ref-type="bibr" rid="B10">10</xref> for AF. Reduced employment participation, where individuals are no longer able to be employed due to their condition, was identified for both HF and MI, but not for AF or HTN. For HF, there was 13% lower employment participation rate (based on those with coronary heart disease).<xref ref-type="bibr" rid="B11">11</xref> The study also showed increased withdrawal of unemployed people from the labor force, especially those aged below 60 years and those engaged in manual work. For MI, there was a 21% lower employment participation [based on those with acute coronary syndrome (ACS) five years after an event].<xref ref-type="bibr" rid="B12">12</xref> As the lower employment participation rates in both the coronary heart disease and ACS studies were based on populations in developed countries, these rates were adjusted by the observed rates of reduced employment participation for those with disability in Europe and Latin America, as reported by the Organization for Economic Cooperation and Development (OECD).<xref ref-type="bibr" rid="B13">13</xref>
				</p>
        <p>Forgone income due to premature death was based on mortality statistics for each condition and the otherwise expected life expectancy according to WHO life tables.<xref ref-type="bibr" rid="B14">14</xref> The anticipated number of years of life left to live by the deceased individual was multiplied first by employment rates and then by the average weekly wage for men and women respectively. The productivity discount rate for future earnings was 5.25% based on the difference between wage growth and inflation (using the annualized average for both over the past five years). The present value of future wages was based on the five-year average real growth rate.<xref ref-type="bibr" rid="B15">15</xref>
				</p>
        <p>Informal care costs were identified for both HF and MI. For HF, each individual was provided an estimated 6.7 hours of informal care per week.<xref ref-type="bibr" rid="B16">16</xref> While there are a variety of sources for this parameter, the study chosen was the most robust methodologically and provided a similar estimate to what could be derived from a study in Latin America.<xref ref-type="bibr" rid="B17">17</xref> For MI, based on a study of coronary heart disease patients, informal care hours were estimated to be 279 hours per year per patient.<xref ref-type="bibr" rid="B18">18</xref>
				</p>
        <p>Taxation revenue foregone was based on the average income tax rate for a single individual and the average indirect tax rate according to the OECD.<xref ref-type="bibr" rid="B19">19</xref><sup>,</sup><xref ref-type="bibr" rid="B20">20</xref> The estimated income tax liability was applied to the estimated total value of forgone earnings to determine the value of taxation lost. An adjustment was also applied for the number working in the &#8216;informal economy&#8217; which is likely to reduce the taxation revenue collected. Exchange rates between USD and the local currency were based on the average of the daily exchange rates from the International Monetary Fund from January 2015 to November 2015.</p>
      </sec>
      <sec>
        <title>Comorbidities</title>
        <p>As multiple conditions could affect one person simultaneously, the total cost of the four conditions was estimated by reviewing literature<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref> that identified the number of individuals with two, three or four concomitant conditions as outlined in <xref ref-type="fig" rid="f1">Figure 1</xref>. Where literature did not outline the concomitant rates between each of the four conditions, the sources were extrapolated until all combinations were derived.</p>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Potential comorbidity combinations accounted for. HF: heart failure; MI: myocardial infarction; AF: atrial fibrillation; HTN: hypertension.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-111-01-0029-80104-gf01.jpg"/></fig>
        </p>
      </sec>
      <sec>
        <title>Cost-effectiveness analysis for HF</title>
        <p>To undertake the analysis, a targeted literature review was carried out to identify either published cost-effectiveness studies which could be adapted to the Brazilian context, or literature which could inform the design of, and inputs to, a cost-effectiveness model. The review identified a relatively recent network meta-analysis and cost-effectiveness analysis of TM and STS programs after discharge in patients with HF, conducted by the National Institute for Health Research in 2013.<xref ref-type="bibr" rid="B24">24</xref> This study was therefore used as the basis for a cost-effectiveness analysis of STS and TM from the perspective of the Sistema Unico de Saude.</p>
      </sec>
      <sec>
        <title>Model structure</title>
        <p>A Markov model was constructed in TreeAge Pro&#169;2015 to evaluate the cost-effectiveness of STS and TM compared with standard care (SC) for a hypothetical cohort of patients discharged in the last 28 days following HF-related hospitalizations. The model as shown in <xref ref-type="fig" rid="f2">Figure 2</xref> considered two different permanent health states, &#8216;alive at home&#8217; and &#8216;dead&#8217; as well as two temporary health states for &#8216;hospitalized due to HF&#8217; and &#8216;hospitalized for all other causes&#8217;. The model is based on monthly cycles with half-cycle corrections.</p>
        <p>
          <fig id="f2">
            <label>Figure 2</label>
            <caption>
              <title>Markov model for recently discharged heart failure (HF) patients.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-111-01-0029-80104-gf02.jpg"/></fig>
        </p>
      </sec>
      <sec>
        <title>Time horizon, duration and discount rate</title>
        <p>As HF is a life-long condition after onset, the model captured a lifetime horizon of 30 years with patients progressing through the model until they either died or reached the end of the 30-year time horizon. It was assumed that the interventions of STS, TM and SC were provided for the full duration of the time horizon, outside of hospitalization. Both health system costs and quality-adjusted life-years (QALYs) were discounted at an annual rate of 5%.</p>
      </sec>
      <sec>
        <title>Data sources</title>
        <sec>
          <title>Efficacy estimates</title>
          <p>The monthly probability of death with SC following a non-fatal hospitalization was based on data from the CHARM study,<xref ref-type="bibr" rid="B25">25</xref> which followed 7,572 patients for a period of 38 months and showed the mortality risk to be the highest after hospital discharge, then decreasing over time. The mean number of HF-related and other (all cause) hospitalizations were based on a published meta-analysis<xref ref-type="bibr" rid="B26">26</xref> and estimated by the National Institute for Health Research.<xref ref-type="bibr" rid="B24">24</xref>
					</p>
          <p>Effectiveness parameters relating to risks of death and hospitalization for STS and TM interventions were based on the hazard ratios for all-cause mortality, all-cause hospitalizations and HF-related hospitalizations during the treatment period. The hazard ratios were estimated from the network meta-analysis by the National Institute for Health Research.<xref ref-type="bibr" rid="B24">24</xref>
					</p>
        </sec>
        <sec>
          <title>Health state utilities</title>
          <p>Health state utilities for SC, STS and TM treatment approaches were based on the previous economic model of TM strategies conducted in a published meta-analysis,<xref ref-type="bibr" rid="B26">26</xref> which used utilities of 0.612 and 0.662 for SC and STS/TM groups, respectively. As with previous economic analyses, a negative adjustment of 0.1 was applied to account for the disutility associated with HF-related hospitalizations.<xref ref-type="bibr" rid="B24">24</xref>
					</p>
        </sec>
        <sec>
          <title>Resource utilization and costs</title>
          <p>STS and TM consist of three main units of healthcare resources:</p>
          <p>
            <list list-type="bullet">
              <list-item>
                <p>devices and equipment within the patient&#8217;s home, which include the device hub, peripherals and communication costs;</p>
              </list-item>
              <list-item>
                <p>maintenance/monitoring in the STS or TM center; and</p>
              </list-item>
              <list-item>
                <p>medical care units to deal with events or alerts, such as GP or nurse visits, or hospital-based outpatient visits.</p>
              </list-item>
            </list>
          </p>
          <p>The units of resources making up the components of SC, STS and TM were based on the published literature, and unit costs were obtained from DATASUS, the Brazilian Ministry of Health&#8217;s data department.</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Cost of illness for heart failure, myocardial infarction, atrial fibrillation and hypertension</title>
        <p>The four heart conditions were estimated to affect approximately 45.7 million people in Brazil, 32.0% of the adult<sup>b</sup> population. After adjusting for comorbidities, heart conditions were conservatively estimated to result in a financial cost of 56.2 billion reais (17.3 billion USD) in 2015 in Brazil. Of this, approximately 62.9% was health system cost. In 2015, the burden of these four conditions comprised approximately 5.5% of total national healthcare expenditure.</p>
      </sec>
      <sec>
        <title>Prevalence/incidence</title>
        <p>HTN has the highest prevalence of the four conditions, followed by HF. As outlined in <xref ref-type="table" rid="t1">Table 1</xref> there were 48.9 million conditions affecting 45.7 million people (some people have more than one condition).</p>
      </sec>
      <sec>
        <title>Economic impact</title>
        <p>MI imposes the greatest financial cost, followed by HF, HTN and, finally, AF. <xref ref-type="table" rid="t2">Table 2</xref> outlines the cost per condition by bearer of cost, demonstrating that each condition impacts individuals, government and society differently. Health costs make up the majority of expenditure for HF, MI and AF, reflecting the nature of Brazil&#8217;s health system.</p>
        <p><xref ref-type="table" rid="t3">Table 3</xref> shows that HTN has the lowest cost per case and MI the highest. While the costs per case seem quite small for HTN, they reflect the total cost of the condition divided by the total number of people with the condition; whether they are receiving treatment or not. This per person cost should be considered in this &#8216;average&#8217; context, rather than reflecting the actual health costs incurred for someone receiving treatment.</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Financial cost of heart conditions in Brazil per case, 2015 (reais)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">
								</th>
                <th align="center">HF</th>
                <th align="center">MI</th>
                <th align="center">AF</th>
                <th align="center">HTN</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Health system cost per case</td>
                <td align="center">5 085 (65%)</td>
                <td align="center">48 118 (72%)</td>
                <td align="center">3 075 (94%)</td>
                <td align="center">25 (14%)</td>
              </tr>
              <tr>
                <td align="left">Productivity cost per case</td>
                <td align="center">2 693 (35%)</td>
                <td align="center">18 678 (28%)</td>
                <td align="center">187 (6%)</td>
                <td align="center">156 (86%)</td>
              </tr>
              <tr>
                <td align="left">Total financial cost per case</td>
                <td align="center">7 777</td>
                <td align="center">66 797</td>
                <td align="center">3 262</td>
                <td align="center">180</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN6">
              <p>HF: heart failure; MI: myocardial infarction; AF: atrial fibrillation; HTN: hypertension.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Loss of wellbeing</title>
        <p>In addition, the heart conditions included impose a substantial wellbeing loss as outlined in <xref ref-type="table" rid="t4">Table 4</xref>. Of the 3.2 million disability adjusted life years (DALYs), adjusted for comorbidities, there are 1.9 million healthy years lost due to disability (YLD) and over 1.3 million years of life lost due to premature mortality (YLL).</p>
        <table-wrap id="t4">
          <label>Table 4</label>
          <caption>
            <title>Loss of wellbeing of heart conditions in Brazil, 2015</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Condition</th>
                <th align="center">YLDs</th>
                <th align="center">YLLs</th>
                <th align="center">DALYs</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">HF</td>
                <td align="center">270 806 (14%)</td>
                <td align="center">251 136 (18%)</td>
                <td align="center">521 941 (16%)</td>
              </tr>
              <tr>
                <td align="left">MI</td>
                <td align="center">2 128 (0.1%)</td>
                <td align="center">1 112 469 (80%)</td>
                <td align="center">1 114 597 (34%)</td>
              </tr>
              <tr>
                <td align="left">AF</td>
                <td align="center">269 014 (14%)</td>
                <td align="center">28 237 (2%)</td>
                <td align="center">297 251 (9%)</td>
              </tr>
              <tr>
                <td align="left">HTN</td>
                <td align="center">1 380 312 (72%)</td>
                <td align="center">
								</td>
                <td align="center">1 380 312 (42%)</td>
              </tr>
              <tr>
                <td align="left">Total (unadjusted)</td>
                <td align="center">1 922 260</td>
                <td align="center">1 391 842</td>
                <td align="center">3 314 102</td>
              </tr>
              <tr>
                <td align="left">Total (adjusted for comorbidities)<xref ref-type="table-fn" rid="TFN8">^</xref>
								</td>
                <td align="center">1 901 386</td>
                <td align="center">1 340 453</td>
                <td align="center">3 241 838</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN7">
              <p>HF: heart failure, MI: myocardial infarction, AF: atrial fibrillation, HTN: hypertension.</p>
            </fn>
            <fn id="TFN8">
              <label>^</label>
              <p>Comorbidity totals do not sum to the total of the individual conditions as one person can have more than one condition and the interaction between conditions causes the total estimate of the four conditions together to vary. YLDs: years lost due to disability; YLLs: years of life lost due to premature mortality; DALYs: disability-adjusted life-years.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Cost-effectiveness analysis for heart failure</title>
        <sec>
          <title>Base case result</title>
          <p>Over the 30-year time horizon, the estimated discounted cumulative costs for the TM and STS interventions were 50,098 and 44,038 reais higher than SC, respectively, but generated an additional 1.91 and 1.63 QALY, respectively. This resulted in an estimated incremental cost-effectiveness ratio (ICER) of 26,437&#8211;81,984 reais/QALY and 27,281 reais/QALY for TM and STS, respectively, compared to SC, noting a willingness to pay (WTP) threshold of 27,328 reais/QALY. The threshold was based on one to three times the GDP per capita of Brazil.<sup>6c</sup> The incremental net monetary benefit was 1,688 reais for TM vs SC and 77 reais for STS vs SC (<xref ref-type="table" rid="t5">Table 5</xref>).</p>
          <table-wrap id="t5">
            <label>Table 5</label>
            <caption>
              <title>Base case result</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="25%"/>
                <col width="25%"/>
                <col width="25%"/>
                <col width="25%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">SC</th>
                  <th align="center">TM</th>
                  <th align="center">STS</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Total costs (reais)</td>
                  <td align="center">5 832</td>
                  <td align="center">55 930</td>
                  <td align="center">49 870</td>
                </tr>
                <tr>
                  <td align="left">Total QALYs</td>
                  <td align="center">3.99</td>
                  <td align="center">5.89</td>
                  <td align="center">5.61</td>
                </tr>
                <tr>
                  <td align="left">Net monetary benefit</td>
                  <td align="center">103 306</td>
                  <td align="center">104 994</td>
                  <td align="center">103 382</td>
                </tr>
                <tr>
                  <td align="left">Incremental costs (reais)</td>
                  <td align="center">
									</td>
                  <td align="center">50 098</td>
                  <td align="center">44 038</td>
                </tr>
                <tr>
                  <td align="left">Incremental QALYs</td>
                  <td align="center">
									</td>
                  <td align="center">1.89</td>
                  <td align="center">1.61</td>
                </tr>
                <tr>
                  <td align="left">Incremental cost (reais) per QALY</td>
                  <td align="center">
									</td>
                  <td align="center">26 437</td>
                  <td align="center">27 281</td>
                </tr>
                <tr>
                  <td align="left">Incremental net monetary benefit</td>
                  <td align="center">
									</td>
                  <td align="center">1 688</td>
                  <td align="center">77</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN9">
                <p>QALY: quality-adjusted life-year; SC: standard care; TM: telemedicine; STS: structured telephone support.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Multivariate sensitivity analysis</title>
          <p>An alternative multivariate scenario analysis was carried out where the costs of TM and STS were varied as well as the health state utilities. In this scenario, the costs of the interventions were increased by 20% and the health state utilities for health states for the strategies were assumed to be the same as those for SC. The results of this scenario analysis are presented in <xref ref-type="table" rid="t6">Table 6</xref>, which shows that the ICER increases from 26,437 to 41,123 reais/QALY for TM vs SC, and increases from 27,281 to 40,309 reais/QALY for STC vs SC.</p>
          <table-wrap id="t6">
            <label>Table 6</label>
            <caption>
              <title>Multivariate sensitivity analysis</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="25%"/>
                <col width="25%"/>
                <col width="25%"/>
                <col width="25%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">SC</th>
                  <th align="center">TM</th>
                  <th align="center">STS</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Total costs (reais)</td>
                  <td align="center">5,832</td>
                  <td align="center">68 891</td>
                  <td align="center">58 538</td>
                </tr>
                <tr>
                  <td align="left">Total QALYs</td>
                  <td align="center">3.99</td>
                  <td align="center">5.45</td>
                  <td align="center">5.30</td>
                </tr>
                <tr>
                  <td align="left">Incremental costs (reais)</td>
                  <td align="center">
									</td>
                  <td align="center">60 059</td>
                  <td align="center">52 706</td>
                </tr>
                <tr>
                  <td align="left">Incremental QALYs</td>
                  <td align="center">
									</td>
                  <td align="center">1.46</td>
                  <td align="center">1.31</td>
                </tr>
                <tr>
                  <td align="left">Incremental cost (reais) per QALY</td>
                  <td align="center">
									</td>
                  <td align="center">41 123</td>
                  <td align="center">40 309</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN10">
                <p>QALY: quality-adjusted life-year; SC: standard care; TM: telemedicine; STS: structured telephone support.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Assuming a WTP threshold of 27,328- 81,984 reais/QALY as above, the cost-effectiveness analysis suggests that TM and STS may be cost-effective treatment options for the management of patients with HF.</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>Our analysis provides the inaugural estimate on the cost of the four conditions across Brazil. By analysing four conditions concurrently in a common framework, we were able to identify the total impact and the impacts of the conditions relative to each other. We have identified that, while MI has significant acute care costs, it does not have as significant informal care costs as HF or HTN. Conversely, HF, while not having as significant acute care costs as MI, has significant productivity losses. While HTN has a low health cost per person, it has a significant total cost due to the large number of people with the condition. Our analysis demonstrates that these conditions can have a large productivity and wellbeing impact beyond their health system costs, which is an important finding from a societal perspective. If policymakers focus only on health costs of a condition, or the relative cost of care per person, they may miss the broader impact that these conditions have across the economy, and the true cost once other fiscal impacts are taken into account.</p>
      <p>While the study has focused on using administrative datasets for health costs, as they are more likely to be reflective of cost allocation by payers, the datasets themselves may not reflect real costs for each condition. For example, the coding and reporting of conditions is subject to clinicians&#8217; individual judgement in nominating the underlying cause, active condition, or chronic condition as the primary condition, and this choice can change the reporting of attributable impacts. A systematic review and meta-analysis of administrative databases for HF identified that datasets do not capture a quarter of cases,<xref ref-type="bibr" rid="B27">27</xref> while a systematic review of electronic medical data for AF identified that there was a disproportionate focus on inpatient data and additional research incorporating outpatient codes, and electrocardiogram data are required to correctly identify the presentations of AF.<xref ref-type="bibr" rid="B28">28</xref> Therefore, while the costs reported are reflective of current clinical judgement and administrative reporting, the cost allocation attributable to each condition can continue to be improved.</p>
      <p>In attributing the relative severity of conditions, their treatment and the impact on related conditions should be considered. Treatment of one of these conditions could alleviate the future development of another costed condition, and the detailed relationships between conditions are still being established. For example, while HTN is understood to be a common risk factor for heart conditions, there is a growing body of evidence that suggests AF is associated with MI.<xref ref-type="bibr" rid="B29">29</xref> Therefore, addressing AF could alleviate future cases of MI and the corresponding cost attributed to MI.</p>
      <p>The primary limitation in this study was comprehensive data availability. There are three key assumptions in the methodology that had to be made and could impact the results, which the reader should keep in mind. First, our health cost estimates are driven by reported hospital statistics for each of the conditions. This is likely to be more appropriate for conditions that have significant acute care management (e.g. MI), but it may under-represent the true cost of conditions that have a greater emphasis on primary care or pharmaceutical management, such as HTN. Second, common to all productivity estimates using a human capital approach, the unemployment rate for Brazil may or may not be sufficiently low to incur a permanent productivity loss. A loss in productivity due to heart conditions from a societal perspective will only equate to a loss in productivity to the economy under the condition that the economy is at the non-accelerating inflation rate of unemployment, so any reduction in hours worked due to illness cannot be replaced in the longer term by employing or increasing hours of other substitute workers. Thirdly, although TM and STS were found to provide beneficial effects in reducing all-cause mortality for recently discharged HF patients, in the original study,<xref ref-type="bibr" rid="B24">24</xref> these results were statistically inconclusive. While this uncertainty around estimates was assessed in the sensitivity analysis, these strategies will need to be re-examined as new evidence emerges.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>This study has found that heart conditions impose significant financial and wellbeing impacts across Brazil, with the four conditions costing $56.2 billion reais in 2015 alone. Prevention or better management of heart conditions could result in significant benefits both in improved wellbeing and economic savings. Telemedicine and structured telephone support are cost effective mechanisms for achieving improvements in the management of heart failure.</p>
      <p>The study was supported by funding from the Novartis Group. The authors are solely responsible for its content.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>This study was funded by Novartis Group.</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 fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
      </fn>
    </fn-group>
    <ack>
      <title>Acknowledgements</title>
      <p>The authors at Deloitte Access Economics designed the study, collected data, performed analysis and wrote the initial draft of the manuscript. All authors read, commented on, and approved the final manuscript. This research is part of a larger study of the Latin American region, with country specific results also identified for Mexico, Chile, Peru, Venezuela, Colombia, Ecuador, Panama and El Salvador. These results for Brazil were presented at ISPOR Vienna (November 2016) and the World Cardiovascular Congress (June 2016).</p>
    </ack>
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  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Os Custos das Doen&#231;as Card&#237;acas no Brasil</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Stevens</surname>
            <given-names>Bryce</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pezzullo</surname>
            <given-names>Lynne</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Verdian</surname>
            <given-names>Lara</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tomlinson</surname>
            <given-names>Josh</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>George</surname>
            <given-names>Alice</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bacal</surname>
            <given-names>Fernando</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff3">
        <label>1</label>
        <institution content-type="original">Deloitte Access Economics Pty Ltd, Austr&#225;lia</institution>
      </aff>
      <aff id="aff4">
        <label>2</label>
        <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - HC-Faculdade de Medicina da USP, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Alice George</bold>, Brindabella Circuit, 2609, Canberra Airport, Canberra &#8211; Austr&#225;lia. E-mail: <email>algeorge@deloitte.com.au</email>, <email>brstevens@deloitte.com.au</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: Stevens B, Pezzullo L, Verdian L; Obten&#231;&#227;o de dados: Stevens B, Tomlinson J; An&#225;lise e interpreta&#231;&#227;o dos dados: Stevens B, Pezzullo L, Verdian L, Tomlinson J; An&#225;lise estat&#237;stica: Stevens B, Tomlinson J; Obten&#231;&#227;o de financiamento: Pezzullo L; Reda&#231;&#227;o do manuscrito: Stevens B, Verdian L, Tomlinson J, George A; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Stevens B, Pezzullo L, Bacal F. </p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>As doen&#231;as card&#237;acas imp&#245;em limita&#231;&#245;es &#224; qualidade de vida nos aspectos f&#237;sicos, sociais, financeiros e de sa&#250;de no Brasil.</p>
        </sec>
        <sec>
          <title>Objetivos:</title>
          <p>Este estudo avaliou o custo de quatro importantes doen&#231;as card&#237;acas no Brasil: hipertens&#227;o, insufici&#234;ncia card&#237;aca, infarto do mioc&#225;rdio e fibrila&#231;&#227;o atrial. Al&#233;m disso, avaliou a rela&#231;&#227;o de custo-efetividade de telemedicina e suporte telef&#244;nico estruturado para o manejo de insufici&#234;ncia card&#237;aca.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Um custo padr&#227;o da estrutura de enfermidade foi usado para avaliar os custos associados &#224;s quatro condi&#231;&#245;es em 2015. Analisou-se a preval&#234;ncia das quatro doen&#231;as e, em caso de infarto do mioc&#225;rdio, tamb&#233;m sua incid&#234;ncia. Avaliaram-se ainda as despesas associadas ao tratamento, a perda de produtividade a partir da redu&#231;&#227;o do emprego, os custos do fornecimento de assist&#234;ncia formal e informal e o bem-estar perdido referentes &#224;s condi&#231;&#245;es. A an&#225;lise teve por base uma revis&#227;o de literatura-alvo, varredura de dados e modelagem. Todos os <italic>inputs</italic> e m&#233;todos foram validados por 15 cl&#237;nicos consultores e outras partes interessadas no Brasil. A an&#225;lise de custo-efetividade baseou-se em uma meta-an&#225;lise e uma avalia&#231;&#227;o econ&#244;mica de programas ap&#243;s a alta de pacientes com insufici&#234;ncia card&#237;aca, considerados a partir da perspectiva do Sistema &#218;nico de Sa&#250;de do Brasil.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Infarto do mioc&#225;rdio acarretou o mais alto custo financeiro (R$ 22,4 bilh&#245;es/6,9 bilh&#245;es de d&#243;lares), seguido de insufici&#234;ncia card&#237;aca (R$ 22,1 bilh&#245;es/6,8 bilh&#245;es de d&#243;lares), hipertens&#227;o (R$ 8 bilh&#245;es/2,5 bilh&#245;es de d&#243;lares) e, finalmente, fibrila&#231;&#227;o atrial (R$ 3,9 bilh&#245;es/1,2 bilh&#227;o de d&#243;lares). Telemedicina e suporte telef&#244;nico estruturado s&#227;o interven&#231;&#245;es custo-efetivas para o aprimoramento do manejo da insufici&#234;ncia card&#237;aca.</p>
        </sec>
        <sec>
          <title>Conclus&#245;es:</title>
          <p>As doen&#231;as card&#237;acas determinam substanciais custos financeiros e perda de bem-estar no Brasil e deveriam ser uma prioridade de sa&#250;de p&#250;blica. </p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Doen&#231;as Cardiovasculares/economia</kwd>
        <kwd>Hipertens&#227;o</kwd>
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Infarto do Mioc&#225;rdio</kwd>
        <kwd>Fibrila&#231;&#227;o Atrial</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>As doen&#231;as card&#237;acas imp&#245;em limita&#231;&#245;es &#224; qualidade de vida relacionadas a aspectos f&#237;sicos, sociais, financeiros e de sa&#250;de dos indiv&#237;duos. Tais doen&#231;as resultam em um custo e um impacto na sociedade devidos &#224;s despesas com tratamento de sa&#250;de, perda de produtividade no emprego, custos do fornecimento de assist&#234;ncia formal e informal e perda de bem-estar. Atualmente as doen&#231;as circulat&#243;rias constituem o maior &#244;nus para a sa&#250;de no mundo, sendo respons&#225;veis por mais de 17 milh&#245;es de mortes a cada ano, o que representa metade de todas as mortes por doen&#231;a n&#227;o transmiss&#237;vel.<xref ref-type="bibr" rid="B1">1</xref>
				</p>
        <p>No Congresso Mundial de Cardiologia e Sa&#250;de Cardiovascular de 2016, a Declara&#231;&#227;o do M&#233;xico para Sa&#250;de Circulat&#243;ria foi assinada pelas principais organiza&#231;&#245;es globais comprometidas em melhorar a sa&#250;de circulat&#243;ria e em reduzir as mortes e a incapacidade por doen&#231;as card&#237;acas e acidente vascular encef&#225;lico no mundo. Tal iniciativa acha-se alinhada com o objetivo claro estabelecido pela Organiza&#231;&#227;o Mundial da Sa&#250;de (OMS) e pelos pa&#237;ses signat&#225;rios para reduzir as mortes por doen&#231;as n&#227;o transmiss&#237;veis em 25% at&#233; 2025.<xref ref-type="bibr" rid="B1">1</xref> Nossa an&#225;lise identifica a carga atual das doen&#231;as card&#237;acas no Brasil e, consequentemente, os potenciais benef&#237;cios econ&#244;micos que resultariam da sua abordagem.</p>
        <p>Este estudo visa avaliar o impacto econ&#244;mico (sistema de sa&#250;de e produtividade) de quatro doen&#231;as card&#237;acas no Brasil, a partir de estimativas do custo anual para 2015: hipertens&#227;o (HTN), infarto do mioc&#225;rdio (IM), fibrila&#231;&#227;o atrial (FA) e insufici&#234;ncia card&#237;aca (IC). Al&#233;m disso, analisa a rela&#231;&#227;o de custo-efetividade de duas interven&#231;&#245;es para IC: telemedicina (TM) e suporte telef&#244;nico estruturado (STE).</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todo</title>
        <p>Esta pesquisa &#233; parte de um estudo maior da Am&#233;rica Latina, com identifica&#231;&#227;o de resultados espec&#237;ficos para alguns pa&#237;ses, como M&#233;xico, Chile, Peru, Venezuela, Col&#244;mbia, Equador, Panam&#225; e El Salvador. Os resultados do Brasil foram apresentados no Congresso Europeu ISPOR em Viena em novembro de 2016 e no Congresso Cardiovascular Mundial em junho de 2016.</p>
        <sec>
          <title>Custo da doen&#231;a</title>
          <p>A an&#225;lise baseou-se em estimar preval&#234;ncia, incid&#234;ncia, perda de bem-estar, custos do sistema de sa&#250;de e perda de produtividade atribu&#237;dos &#224;s quatro doen&#231;as card&#237;acas. As estimativas de custo total foram ajustadas com base na comorbidade das condi&#231;&#245;es. Subjacente ao estudo, houve uma pesquisa na literatura com termos de busca associados com pa&#237;s, regi&#227;o, epidemiologia e impacto econ&#244;mico das quatro doen&#231;as card&#237;acas. As fontes inclu&#237;ram PubMed, <italic>websites</italic> do governo, do sistema de sa&#250;de e de organiza&#231;&#245;es de pacientes, assim como engenhos de busca da Internet em geral.</p>
        </sec>
        <sec>
          <title>Preval&#234;ncia/incid&#234;ncia das doen&#231;as</title>
          <p>A <xref ref-type="table" rid="t7">Tabela 1</xref> apresenta as fontes usadas para estimar a preval&#234;ncia ou incid&#234;ncia das condi&#231;&#245;es. Sempre que poss&#237;vel, utilizaram-se taxas espec&#237;ficas do Brasil. Todas as estimativas foram checadas com as partes interessadas entrevistadas para o projeto. As taxas identificadas foram aplicadas &#224;s proje&#231;&#245;es dos Prospectos sobre Popula&#231;&#227;o Mundial das Na&#231;&#245;es Unidas.<xref ref-type="bibr" rid="B2">2</xref>
					</p>
          <table-wrap id="t7">
            <label>Tabela 1</label>
            <caption>
              <title>N&#250;mero de pessoas com as quatro condi&#231;&#245;es card&#237;acas no Brasil, 2015</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="33%"/>
                <col width="33%"/>
                <col width="33%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Condi&#231;&#227;o</th>
                  <th align="center">N&#250;mero de pessoas</th>
                  <th align="center">Porcentagem da popula&#231;&#227;o adulta<xref ref-type="table-fn" rid="TFN11">*</xref>
									</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">IC</td>
                  <td align="center">2.845.722</td>
                  <td align="center">2,0</td>
                </tr>
                <tr>
                  <td align="left">IM</td>
                  <td align="center">334.978</td>
                  <td align="center">0,2</td>
                </tr>
                <tr>
                  <td align="left">FA</td>
                  <td align="center">1.202.151</td>
                  <td align="center">0,8</td>
                </tr>
                <tr>
                  <td align="left">HTN</td>
                  <td align="center">44.526.201</td>
                  <td align="center">31,2</td>
                </tr>
                <tr>
                  <td align="left">Total das condi&#231;&#245;es</td>
                  <td align="center">48.909.052</td>
                  <td align="center">34,3</td>
                </tr>
                <tr>
                  <td align="left">Total de pessoas com qualquer condi&#231;&#227;o (i.e., respons&#225;vel por comorbidades)</td>
                  <td align="center">45.658.048</td>
                  <td align="center">32,0</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN11">
                <label>*</label>
                <p>Porcentagem reflete a evid&#234;ncia de estudos com popula&#231;&#245;es com idade m&#237;nima de 20 anos. IC: insufici&#234;ncia card&#237;aca; IM: infarto do mioc&#225;rdio, FA: fibrila&#231;&#227;o atrial; HTN: hipertens&#227;o.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Perda de bem-estar</title>
          <p>Os pesos da incapacidade tiveram por base os estudos sobre Carga Global de Doen&#231;a da OMS<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> (<xref ref-type="table" rid="t8">Tabela 2</xref>). Foram ent&#227;o multiplicados pelas estimativas de preval&#234;ncia para que se identificassem os anos perdidos em virtude de incapacidade em 2015. Os anos de vida perdidos foram baseados na mortalidade relatada para cada condi&#231;&#227;o.</p>
          <table-wrap id="t8">
            <label>Tabela 2</label>
            <caption>
              <title>Custo financeiro das condi&#231;&#245;es card&#237;acas no Brasil, 2015 (milh&#245;es de reais)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
                <col width="14%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Categoria</th>
                  <th align="center">IC</th>
                  <th align="center">IM</th>
                  <th align="center">FA</th>
                  <th align="center">HTN</th>
                  <th align="center">Total (n&#227;o ajustado)</th>
                  <th align="center">Total (ajustado para comorbidades)<sup><xref ref-type="table-fn" rid="TFN15">^</xref></sup></th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left" rowspan="2">Custos do sistema de sa&#250;de</td>
                  <td align="center">14.469</td>
                  <td align="center">16.119</td>
                  <td align="center">3.697</td>
                  <td align="center">1.098</td>
                  <td align="center">35.382</td>
                  <td align="center">35.382</td>
                </tr>
                <tr>
                  <td align="center">65%</td>
                  <td align="center">72%</td>
                  <td align="center">94%</td>
                  <td align="center">14%</td>
                  <td align="center">63%</td>
                  <td align="center">63%</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Perda de produtividade</td>
                  <td align="center">7.663</td>
                  <td align="center">6.257</td>
                  <td align="center">225</td>
                  <td align="center">6.927</td>
                  <td align="center">21.071</td>
                  <td align="center">20.858</td>
                </tr>
                <tr>
                  <td align="center">35%</td>
                  <td align="center">28%</td>
                  <td align="center">6%</td>
                  <td align="center">86%</td>
                  <td align="center">37%</td>
                  <td align="center">37%</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Renda perdida por indiv&#237;duo<xref ref-type="table-fn" rid="TFN13">*</xref>
									</td>
                  <td align="center">3.528</td>
                  <td align="center">4.540</td>
                  <td align="center">156</td>
                  <td align="center">2.063</td>
                  <td align="center">10.287</td>
                  <td align="center">10.196</td>
                </tr>
                <tr>
                  <td align="center">16%</td>
                  <td align="center">20%</td>
                  <td align="center">4%</td>
                  <td align="center">26%</td>
                  <td align="center">18%</td>
                  <td align="center">18%</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Renda perdida por neg&#243;cio<xref ref-type="table-fn" rid="TFN13">*</xref>
									</td>
                  <td align="center">333</td>
                  <td align="center">403</td>
                  <td align="center">31</td>
                  <td align="center">4.378</td>
                  <td align="center">5.145</td>
                  <td align="center">5.050</td>
                </tr>
                <tr>
                  <td align="center">2%</td>
                  <td align="center">2%</td>
                  <td align="center">1%</td>
                  <td align="center">55%</td>
                  <td align="center">9%</td>
                  <td align="center">9%</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Custo de oportunidade da assist&#234;ncia informal por fam&#237;lia/amigos</td>
                  <td align="center">2.404</td>
                  <td align="center">196</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">2.600</td>
                  <td align="center">2.596</td>
                </tr>
                <tr>
                  <td align="center">11%</td>
                  <td align="center">1%</td>
                  <td align="center">
									</td>
                  <td align="center">
									</td>
                  <td align="center">5%</td>
                  <td align="center">5%</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Receitas fiscais perdidas pelo governo<xref ref-type="table-fn" rid="TFN14">**</xref>
									</td>
                  <td align="center">1.399</td>
                  <td align="center">1.117</td>
                  <td align="center">37</td>
                  <td align="center">486</td>
                  <td align="center">3.039</td>
                  <td align="center">3.016</td>
                </tr>
                <tr>
                  <td align="center">6%</td>
                  <td align="center">5%</td>
                  <td align="center">1%</td>
                  <td align="center">6%</td>
                  <td align="center">5%</td>
                  <td align="center">5%</td>
                </tr>
                <tr>
                  <td align="left">Custo total</td>
                  <td align="center">22.132</td>
                  <td align="center">22.375</td>
                  <td align="center">3.921</td>
                  <td align="center">8.025</td>
                  <td align="center">56.454</td>
                  <td align="center">56.241</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN12">
                <p>Resultados em milh&#245;es de reais.</p>
              </fn>
              <fn id="TFN13">
                <label>*</label>
                <p>Resultado de absente&#237;smo, participa&#231;&#227;o reduzida no emprego e mortalidade prematura.</p>
              </fn>
              <fn id="TFN14">
                <label>**</label>
                <p>Devido &#224; redu&#231;&#227;o da renda de indiv&#237;duos com doen&#231;as card&#237;acas e seus cuidadores.</p>
              </fn>
              <fn id="TFN15">
                <label>^</label>
                <p>O total de comorbidades n&#227;o chega ao total de condi&#231;&#245;es individuais, pois uma pessoa pode ter mais de uma condi&#231;&#227;o e a intera&#231;&#227;o entre as condi&#231;&#245;es causa a varia&#231;&#227;o na estimativa total das quatro condi&#231;&#245;es juntas. IC: insufici&#234;ncia card&#237;aca; IM: infarto do mioc&#225;rdio; FA: fibrila&#231;&#227;o atrial; HTN: hipertens&#227;o.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Custos do sistema de sa&#250;de</title>
          <p>As altas e a perman&#234;ncia m&#233;dia de cada uma das quatro condi&#231;&#245;es<xref ref-type="bibr" rid="B5">5</xref> foram combinadas &#224;s estimativas de custo para cada uma delas<xref ref-type="bibr" rid="B5">5</xref> para estimar seu peso individual no sistema de sa&#250;de como parte de todas as doen&#231;as tratadas. Isso foi ent&#227;o combinado com uma estimativa do total relevante de gasto com sa&#250;de no Brasil<xref ref-type="bibr" rid="B6">6</xref> para resultar no custo de tratamento de cada uma das quatro condi&#231;&#245;es. Os custos de sa&#250;de foram estimados a partir da perspectiva dos pagadores da assist&#234;ncia &#224; sa&#250;de, tanto p&#250;blicos quanto privados. A decomposi&#231;&#227;o dos custos teve por base aqueles relatados para o Brasil.<xref ref-type="bibr" rid="B7">7</xref> Este m&#233;todo reflete mais adequadamente os impactos com base no n&#250;mero, na perman&#234;ncia e na intensidade do custo de cada condi&#231;&#227;o especificamente para o Brasil. Entretanto, dados sobre as despesas de sa&#250;de espec&#237;ficas de cada condi&#231;&#227;o n&#227;o est&#227;o dispon&#237;veis para outros componentes do sistema de sa&#250;de (e.g., cuidado prim&#225;rio). Assim, admitiu-se que a parte de cada condi&#231;&#227;o na despesa total do sistema de sa&#250;de fosse a mesma que a sua cota no total da despesa hospitalar.</p>
        </sec>
        <sec>
          <title>Perda de produtividade</title>
          <p>Consistente com o crit&#233;rio de &#8216;emprego pleno ou quase pleno&#8217;,<sup>a</sup> adotou-se uma abordagem de capital humano para estimar as perdas de produtividade. C&#225;lculos envolvendo perda de produtividade foram baseados em taxas de emprego por faixa et&#225;ria e sexo. Admitiu-se que portadores de doen&#231;as card&#237;acas, na aus&#234;ncia da condi&#231;&#227;o, apresentavam a mesma probabilidade de estarem empregados que os outros de mesmo sexo e faixa et&#225;ria. A renda salarial n&#227;o recebida foi baseada em dados salariais para o Brasil.<xref ref-type="bibr" rid="B7">7</xref>
					</p>
          <p>Absente&#237;smo associou-se com todas as condi&#231;&#245;es. Para IC, foi estimado em 12,66 dias por ano para aqueles com IC NYHA III/IV, e em 3,04 dias por ano para aqueles com IC NYHA I/II.<xref ref-type="bibr" rid="B8">8</xref> O absente&#237;smo foi estimado em 3,03 dias por ano<xref ref-type="bibr" rid="B9">9</xref> para HTN, 75 dias por ano para pacientes hospitalizados<xref ref-type="bibr" rid="B9">9</xref> com IM, e 2,1 dias por ano<xref ref-type="bibr" rid="B10">10</xref> para FA. Identificou-se redu&#231;&#227;o de participa&#231;&#227;o no emprego, com indiv&#237;duos impossibilitados de continuar empregados devido &#224; sua condi&#231;&#227;o, para IC e IM, mas n&#227;o para FA ou HTN. A taxa de participa&#231;&#227;o no emprego para IC foi 13% mais baixa (tendo por base indiv&#237;duos com doen&#231;a arterial coronariana).<xref ref-type="bibr" rid="B11">11</xref> Al&#233;m disso, o estudo mostrou aumento da sa&#237;da de indiv&#237;duos desempregados da for&#231;a de trabalho, em especial aqueles com menos de 60 anos e aqueles engajados em trabalho manual. Quanto ao IM, a participa&#231;&#227;o no emprego foi 21% mais baixa, tendo por base indiv&#237;duos com s&#237;ndrome coronariana aguda (SCA) cinco anos ap&#243;s um evento.<xref ref-type="bibr" rid="B12">12</xref> Como as taxas de participa&#231;&#227;o no emprego mais baixas tanto para doen&#231;a arterial coronariana quanto SCA foram obtidas em estudos conduzidos com popula&#231;&#245;es de pa&#237;ses desenvolvidos, tais taxas foram ajustadas pelas taxas observadas de redu&#231;&#227;o de participa&#231;&#227;o no emprego para aqueles com incapacidade na Europa e Am&#233;rica Latina, segundo relato da Organiza&#231;&#227;o para Coopera&#231;&#227;o e Desenvolvimento Econ&#244;mico (OCDE).<xref ref-type="bibr" rid="B13">13</xref>
					</p>
          <p>Renda n&#227;o recebida devido a morte prematura foi baseada em estat&#237;stica de mortalidade para cada condi&#231;&#227;o e expectativa de vida segundo as tabelas de vida da OMS.<xref ref-type="bibr" rid="B14">14</xref> O n&#250;mero esperado de anos de vida que um indiv&#237;duo falecido deixou de viver foi multiplicado primeiro pelas taxas de emprego e depois pela m&#233;dia do sal&#225;rio semanal para homens e mulheres. A taxa de desconto de produtividade para ganhos futuros foi de 5,25% com base na diferen&#231;a entre o crescimento do sal&#225;rio e a infla&#231;&#227;o, usando a m&#233;dia anualizada para ambos nos &#250;ltimos cinco anos. O valor presente dos sal&#225;rios futuros foi baseado na taxa de crescimento real m&#233;dia de cinco anos.<xref ref-type="bibr" rid="B15">15</xref>
					</p>
          <p>Os custos de assist&#234;ncia informal foram identificados para IC e IM. Para IC, atribuiu-se a cada indiv&#237;duo uma estimativa de 6,7 horas de assist&#234;ncia informal por semana.<xref ref-type="bibr" rid="B16">16</xref> Embora haja uma variedade de fontes para tal par&#226;metro, o estudo escolhido foi o mais robusto do ponto de vista metodol&#243;gico, fornecendo uma estimativa similar &#224;quela que poderia ser obtida de um estudo na Am&#233;rica Latina.<xref ref-type="bibr" rid="B17">17</xref> Quanto ao IM, com base em um estudo de pacientes com doen&#231;a arterial coronariana, as horas de assist&#234;ncia informal foram estimadas em 279 por ano por paciente.<xref ref-type="bibr" rid="B18">18</xref>
					</p>
          <p>A receita de tributa&#231;&#227;o n&#227;o recebida teve por base a m&#233;dia da taxa de imposto de renda para um &#250;nico indiv&#237;duo e a m&#233;dia da taxa de imposto indireto segundo a OCDE.<xref ref-type="bibr" rid="B19">19</xref><sup>,</sup><xref ref-type="bibr" rid="B20">20</xref> A responsabilidade fiscal estimada foi aplicada ao valor total estimado de ganhos perdidos para determinar o valor da tributa&#231;&#227;o perdida. Aplicou-se ainda um ajuste para o n&#250;mero de indiv&#237;duos trabalhando na &#8216;economia informal&#8217;, que pode reduzir as receitas fiscais arrecadadas. As taxas de c&#226;mbio entre o d&#243;lar americano e a moeda local foram baseadas na m&#233;dia das taxas de c&#226;mbio di&#225;rias do Fundo Monet&#225;rio Internacional de janeiro a novembro de 2015.</p>
        </sec>
        <sec>
          <title>Comorbidades</title>
          <p>Como m&#250;ltiplas condi&#231;&#245;es podem afetar uma pessoa simultaneamente, o custo total das quatro condi&#231;&#245;es foi estimado ao revisar a literatura,<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref> que identificou o n&#250;mero de indiv&#237;duos com duas, tr&#234;s ou quatro condi&#231;&#245;es concomitantes como mostra a <xref ref-type="fig" rid="f3">Figura 1</xref>. Onde a literatura n&#227;o delineou as taxas concomitantes para as quatro condi&#231;&#245;es, as fontes foram extrapoladas at&#233; que todas as combina&#231;&#245;es fossem derivadas.</p>
          <p>
            <fig id="f3">
              <label>Figura 1</label>
              <caption>
                <title>Potenciais combina&#231;&#245;es de comorbidades.IC: insufici&#234;ncia card&#237;aca; IM: infarto do mioc&#225;rdio; FA: fibrila&#231;&#227;o atrial; HTN: hipertens&#227;o.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-111-01-0029-80104-gf01-pt.jpg"/></fig>
          </p>
        </sec>
        <sec>
          <title>An&#225;lise de custo-efetividade para IC</title>
          <p>Para a an&#225;lise, a literatura-alvo foi revisada para identificar estudos de custo-efetividade que pudessem ser adaptados ao contexto mexicano, ou que pudessem informar o desenho do modelo de custo-efetividade e seus <italic>inputs</italic>. A revis&#227;o identificou uma meta-an&#225;lise de rede relativamente recente e an&#225;lise de custo-efetividade de programas de TM e STE ap&#243;s a alta de pacientes com IC, conduzidas pelo Instituto Nacional para Pesquisa em Sa&#250;de em 2013.<xref ref-type="bibr" rid="B24">24</xref> Esse estudo foi usado como base para a an&#225;lise de custo-efetividade de STE e TM a partir da perspectiva do Sistema &#218;nico de Sa&#250;de.</p>
        </sec>
        <sec>
          <title>Estrutura do modelo</title>
          <p>Construiu-se um modelo de Markov em TreeAge Pro&#169;2015 para avaliar a rela&#231;&#227;o de custo-efetividade de STE e TM em compara&#231;&#227;o ao cuidado padr&#227;o (CP) para uma hipot&#233;tica coorte de pacientes que receberam alta nos 28 dias que se seguiram &#224; hospitaliza&#231;&#227;o relacionada a IC. O modelo mostrado na <xref ref-type="fig" rid="f4">Figura 2</xref> considerou dois diferentes estados de sa&#250;de permanentes, &#8216;vivo em casa&#8217; e &#8216;falecido&#8217;, al&#233;m de dois estados de sa&#250;de tempor&#225;rios, &#8216;hospitaliza&#231;&#227;o por IC&#8217; e &#8216;hospitaliza&#231;&#227;o por todas as outras causas&#8217;. O modelo foi baseado em ciclos mensais com corre&#231;&#245;es na metade do ciclo.</p>
          <p>
            <fig id="f4">
              <label>Figura 2</label>
              <caption>
                <title>Modelo de Markov para pacientes com insufici&#234;ncia card&#237;aca (IC) com alta recente.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-111-01-0029-80104-gf02-pt.jpg"/></fig>
          </p>
        </sec>
        <sec>
          <title>Horizonte de tempo, dura&#231;&#227;o e taxa de desconto</title>
          <p>Como a IC &#233; uma condi&#231;&#227;o para toda a vida ap&#243;s sua instala&#231;&#227;o, o modelo capturou um horizonte de tempo de vida de 30 anos com os pacientes progredindo no modelo at&#233; que morressem ou chegassem ao final do horizonte de tempo de 30 anos. Admitiu-se que as interven&#231;&#245;es de STE, TM e CP fossem oferecidas durante toda a dura&#231;&#227;o do horizonte de tempo, fora da hospitaliza&#231;&#227;o. Tanto os custos do sistema de sa&#250;de quanto os anos de vida ajustados por qualidade (QALY) foram descontados a uma taxa anual de 5%.</p>
        </sec>
        <sec>
          <title>Fontes de dados</title>
          <sec>
            <title>Estimativas de efic&#225;cia</title>
            <p>A probabilidade mensal de morte com CP seguinte a uma hospitaliza&#231;&#227;o n&#227;o fatal baseou-se em dados do estudo CHARM,<xref ref-type="bibr" rid="B25">25</xref> que acompanhou 7.572 pacientes por um per&#237;odo de 38 meses, tendo mostrado o mais alto risco de mortalidade ap&#243;s a alta hospitalar, com redu&#231;&#227;o ao longo do tempo. O n&#250;mero m&#233;dio de hospitaliza&#231;&#245;es relacionadas a IC e a todas as outras causas baseou-se em uma meta-an&#225;lise,<xref ref-type="bibr" rid="B26">26</xref> tendo sido estimado pelo Instituto Nacional para Pesquisa em Sa&#250;de.<xref ref-type="bibr" rid="B24">24</xref>
						</p>
            <p>Os par&#226;metros de efetividade relacionados aos riscos de morte e hospitaliza&#231;&#227;o para as interven&#231;&#245;es de STE e TM basearam-se em raz&#245;es de risco para mortalidade por todas as causas, hospitaliza&#231;&#245;es por todas as causas e hospitaliza&#231;&#245;es relacionadas a IC durante o per&#237;odo de tratamento. As raz&#245;es de risco foram estimadas a partir da meta-an&#225;lise de rede do Instituto Nacional para Pesquisa em Sa&#250;de.<xref ref-type="bibr" rid="B24">24</xref>
						</p>
          </sec>
          <sec>
            <title>Estados de sa&#250;de</title>
            <p>Os valores de estado de sa&#250;de para abordagens de tratamento com CP, STE e TM basearam-se no modelo econ&#244;mico pr&#233;vio de estrat&#233;gias de TM conduzidas em uma meta-an&#225;lise publicada,<xref ref-type="bibr" rid="B26">26</xref> que usou os &#237;ndices de estado de sa&#250;de de 0,612 e 0,662 para os grupos CP e STE/TM, respectivamente. Como em an&#225;lises econ&#244;micas pr&#233;vias, um ajuste negativo de 0,1 foi aplicado para dar conta da &#8216;desutilidade&#8217; associada com hospitaliza&#231;&#245;es relacionadas &#224; IC.<xref ref-type="bibr" rid="B24">24</xref>
						</p>
          </sec>
          <sec>
            <title>Utiliza&#231;&#227;o de recursos e custos</title>
            <p>O STE e a TM consistem de tr&#234;s principais unidades de recursos de assist&#234;ncia &#224; sa&#250;de:</p>
            <p>
              <list list-type="bullet">
                <list-item>
                  <p>dispositivos e equipamento dentro da casa do paciente, que incluem o ponto central do dispositivo, perif&#233;ricos e custos de comunica&#231;&#227;o;</p>
                </list-item>
                <list-item>
                  <p>manuten&#231;&#227;o/monitoramento no centro de STE ou TM; e</p>
                </list-item>
                <list-item>
                  <p>unidades de assist&#234;ncia m&#233;dica para lidar com eventos ou alertas, como consultas de cl&#237;nicos gerais ou enfermeiros, ou consultas ambulatoriais em hospitais.</p>
                </list-item>
              </list>
            </p>
            <p>As unidades de recursos que comp&#245;em o CP, o STE e a TM foram baseadas na literatura e seus custos foram obtidos no DATASUS, do departamento de inform&#225;tica do Minist&#233;rio da Sa&#250;de brasileiro.</p>
          </sec>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Custo da enfermidade por insufici&#234;ncia card&#237;aca, infarto do mioc&#225;rdio, fibrila&#231;&#227;o atrial e hipertens&#227;o</title>
          <p>Estima-se que as quatro doen&#231;as card&#237;acas afetem aproximadamente 45,7 milh&#245;es de pessoas no Brasil, 32% da popula&#231;&#227;o adulta.<sup>b</sup> Ap&#243;s ajustar para comorbidades, estimou-se, de maneira conservativa, que as doen&#231;as card&#237;acas resultaram em um custo financeiro de R$ 56,2 bilh&#245;es (17,3 bilh&#245;es de d&#243;lares) em 2015 no Brasil. Desses, cerca de 62,9% devem-se a custo do sistema de sa&#250;de. Em 2015, a carga dessas quatro condi&#231;&#245;es correspondeu a aproximadamente 5,5% do total nacional da despesa com assist&#234;ncia &#224; sa&#250;de.</p>
        </sec>
        <sec>
          <title>Preval&#234;ncia/incid&#234;ncia</title>
          <p>Das quatro condi&#231;&#245;es, a HTN apresenta a maior preval&#234;ncia, seguida pela IC. A <xref ref-type="table" rid="t7">Tabela 1</xref> mostra 48,9 milh&#245;es de condi&#231;&#245;es afetando 45,7 milh&#245;es de pessoas, algumas das quais tinham mais de uma condi&#231;&#227;o.</p>
        </sec>
        <sec>
          <title>Impacto econ&#244;mico</title>
          <p>O IM imp&#245;e o maior custo financeiro, seguindo pela IC, HTN e finalmente FA. A <xref ref-type="table" rid="t8">Tabela 2</xref> mostra o custo por condi&#231;&#227;o por componente de custo, demonstrando que cada condi&#231;&#227;o impacta indiv&#237;duos, governos e sociedade de maneira diferente. Os custos de sa&#250;de constituem a maior parte da despesa por IC, IM e FA, refletindo a natureza do sistema de sa&#250;de do Brasil.</p>
          <p>A <xref ref-type="table" rid="t9">Tabela 3</xref> mostra que a HTN tem o menor custo por caso, e o IM, o maior. Embora os custos por caso pare&#231;am pequenos para HTN, refletem o custo total da condi&#231;&#227;o dividido pelo n&#250;mero total de pessoas com a condi&#231;&#227;o, estejam ou n&#227;o recebendo tratamento. Esse custo por pessoa deve ser considerado nesse contexto &#8216;m&#233;dio&#8217;, em lugar de refletir os verdadeiros custos de sa&#250;de a que fica sujeito um indiv&#237;duo em tratamento.</p>
          <table-wrap id="t9">
            <label>Tabela 3</label>
            <caption>
              <title>Custo financeiro das condi&#231;&#245;es card&#237;acas no Brasil por caso, 2015 (reais).</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">
									</th>
                  <th align="center">IC</th>
                  <th align="center">IM</th>
                  <th align="center">FA</th>
                  <th align="center">HTN</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Custo do sistema de sa&#250;de por caso</td>
                  <td align="center">5.085 (65%)</td>
                  <td align="center">48.118 (72%)</td>
                  <td align="center">3.075 (94%)</td>
                  <td align="center">25 (14%)</td>
                </tr>
                <tr>
                  <td align="left">Custo da produtividade por caso</td>
                  <td align="center">2.693 (35%)</td>
                  <td align="center">18.678 (28%)</td>
                  <td align="center">187 (6%)</td>
                  <td align="center">156 (86%)</td>
                </tr>
                <tr>
                  <td align="left">Custo financeiro total por caso</td>
                  <td align="center">7.777</td>
                  <td align="center">66.797</td>
                  <td align="center">3.262</td>
                  <td align="center">180</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN16">
                <p>IC: insufici&#234;ncia card&#237;aca; IM: infarto do mioc&#225;rdio; FA: fibrila&#231;&#227;o atrial; HTN: hipertens&#227;o.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Perda de bem-estar</title>
          <p>Al&#233;m disso, as doen&#231;as card&#237;acas analisadas imp&#245;em uma substancial perda de bem-estar, como mostra a <xref ref-type="table" rid="t10">Tabela 4</xref>. Dos 3,2 milh&#245;es de anos de vida perdidos ajustados por incapacidade (DALY), ajustados para comorbidades, h&#225; 1,9 milh&#227;o de anos de vida saud&#225;vel perdidos em virtude de incapacidade (YLD) e mais de 1,3 milh&#227;o de anos de vida perdidos em decorr&#234;ncia de morte prematura (YLL).</p>
          <table-wrap id="t10">
            <label>Tabela 4</label>
            <caption>
              <title>Perda de bem-estar das condi&#231;&#245;es card&#237;acas no Brasil, 2015.</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="25%"/>
                <col width="25%"/>
                <col width="25%"/>
                <col width="25%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Condi&#231;&#227;o</th>
                  <th align="center">YLD</th>
                  <th align="center">YLL</th>
                  <th align="center">DALY</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">IC</td>
                  <td align="center">270.806 (14%)</td>
                  <td align="center">251.136 (18%)</td>
                  <td align="center">521.941 (16%)</td>
                </tr>
                <tr>
                  <td align="left">IM</td>
                  <td align="center">2.128 (0,1%)</td>
                  <td align="center">1.112.469 (80%)</td>
                  <td align="center">1.114.597 (34%)</td>
                </tr>
                <tr>
                  <td align="left">FA</td>
                  <td align="center">269.014 (14%)</td>
                  <td align="center">28.237 (2%)</td>
                  <td align="center">297.251 (9%)</td>
                </tr>
                <tr>
                  <td align="left">HTN</td>
                  <td align="center">1.380.312 (72%)</td>
                  <td align="center">
									</td>
                  <td align="center">1.380.312 (42%)</td>
                </tr>
                <tr>
                  <td align="left">Total (n&#227;o ajustado)</td>
                  <td align="center">1.922.260</td>
                  <td align="center">1.391.842</td>
                  <td align="center">3.314.102</td>
                </tr>
                <tr>
                  <td align="left">Total (ajustado por comorbidades)<sup><xref ref-type="table-fn" rid="TFN18">^</xref></sup></td>
                  <td align="center">1.901.386</td>
                  <td align="center">1.340.453</td>
                  <td align="center">3.241.838</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN17">
                <p>IC: insufici&#234;ncia card&#237;aca, IM: infarto do mioc&#225;rdio, FA: fibrila&#231;&#227;o atrial, HTN: hipertens&#227;o.</p>
              </fn>
              <fn id="TFN18">
                <label>^</label>
                <p>O total de comorbidades n&#227;o chega ao total de condi&#231;&#245;es individuais, pois uma pessoa pode ter mais de uma condi&#231;&#227;o e a intera&#231;&#227;o entre as condi&#231;&#245;es causa a varia&#231;&#227;o na estimativa total das quatro condi&#231;&#245;es juntas. YLD: anos de vida saud&#225;vel perdidos em virtude de incapacidade; YLL: anos de vida perdidos em decorr&#234;ncia de morte prematura; DALY: anos de vida perdidos ajustados por incapacidade. </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>An&#225;lise de custo-efetividade para insufici&#234;ncia card&#237;aca</title>
          <sec>
            <title>Resultado de caso-base</title>
            <p>Considerando o horizonte de tempo de 30 anos, a estimativa dos custos acumulados descontados para as interven&#231;&#245;es de TM e STE excedeu o de CP em R$ 50.098 e R$ 44.038, respectivamente, mas gerou QALY adicional de 1,91 e 1,63, respectivamente. Isso resultou em uma raz&#227;o custo-efetividade incremental (RCEI) estimada de R$ 26.437&#8211;81.984/QALY e R$ 27.281/QALY para TM e STE, respectivamente, em compara&#231;&#227;o a CP, salientando-se um limiar de vontade de pagar (WTP) de R$ 27.328/QALY. O limiar foi baseado em uma a tr&#234;s vezes o PIB per capita do Brasil.<sup>6c</sup> O benef&#237;cio monet&#225;rio l&#237;quido incremental foi de R$1.688 para TM vs CP e de R$ 77 para STE vs CP (<xref ref-type="table" rid="t11">Tabela 5</xref>).</p>
            <table-wrap id="t11">
              <label>Tabela 5</label>
              <caption>
                <title>Resultado de caso-base.</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col width="25%"/>
                  <col width="25%"/>
                  <col width="25%"/>
                  <col width="25%"/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">
										</th>
                    <th align="center">CP</th>
                    <th align="center">TM</th>
                    <th align="center">STE</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td align="left">Custo total (R$)</td>
                    <td align="center">5.832</td>
                    <td align="center">55.930</td>
                    <td align="center">49.870</td>
                  </tr>
                  <tr>
                    <td align="left">QALY total</td>
                    <td align="center">3,99</td>
                    <td align="center">5,89</td>
                    <td align="center">5,61</td>
                  </tr>
                  <tr>
                    <td align="left">Benef&#237;cio monet&#225;rio l&#237;quido</td>
                    <td align="center">103.306</td>
                    <td align="center">104.994</td>
                    <td align="center">103.382</td>
                  </tr>
                  <tr>
                    <td align="left">Custos incrementais (R$)</td>
                    <td align="center">
										</td>
                    <td align="center">50.098</td>
                    <td align="center">44.038</td>
                  </tr>
                  <tr>
                    <td align="left">QALY incremental</td>
                    <td align="center">
										</td>
                    <td align="center">1,89</td>
                    <td align="center">1,61</td>
                  </tr>
                  <tr>
                    <td align="left">Custo incremental (R$) por QALY</td>
                    <td align="center">
										</td>
                    <td align="center">26.437</td>
                    <td align="center">27.281</td>
                  </tr>
                  <tr>
                    <td align="left">Benef&#237;cio monet&#225;rio l&#237;quido incremental</td>
                    <td align="center">
										</td>
                    <td align="center">1.688</td>
                    <td align="center">77</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN19">
                  <p>QALY: anos de vida ajustados por qualidade; CP: cuidado padr&#227;o; TM: telemedicina; STE: suporte telef&#244;nico estruturado.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </sec>
          <sec>
            <title>An&#225;lise multivariada de sensibilidade</title>
            <p>Conduziu-se uma an&#225;lise multivariada de cen&#225;rio alternativo em que os custos de TM e de STE eram variados, assim como os estados de sa&#250;de. Nesse cen&#225;rio, os custos das interven&#231;&#245;es foram aumentados em 20% e assumiu-se que os valores dos estados de sa&#250;de para as estrat&#233;gias eram os mesmos que aqueles para CP. Os resultados da an&#225;lise desse cen&#225;rio s&#227;o apresentados na <xref ref-type="table" rid="t12">Tabela 6</xref>, que mostra que a RCEI aumenta de R$ 26.437/QALY para R$ 41.123/QALY para TM vs CP, e de R$ 27.281/QALY para R$ 40.309/QALY para STE vs CP.</p>
            <table-wrap id="t12">
              <label>Tabela 6</label>
              <caption>
                <title>An&#225;lise multivariada de sensibilidade</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col width="25%"/>
                  <col width="25%"/>
                  <col width="25%"/>
                  <col width="25%"/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">
										</th>
                    <th align="center">CP</th>
                    <th align="center">TM</th>
                    <th align="center">STE</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td align="left">Custo total (R$)</td>
                    <td align="center">5.832</td>
                    <td align="center">68.891</td>
                    <td align="center">58.538</td>
                  </tr>
                  <tr>
                    <td align="left">QALY total</td>
                    <td align="center">3,99</td>
                    <td align="center">5,45</td>
                    <td align="center">5,30</td>
                  </tr>
                  <tr>
                    <td align="left">Custos incrementais (R$)</td>
                    <td align="center">
										</td>
                    <td align="center">60.059</td>
                    <td align="center">52.706</td>
                  </tr>
                  <tr>
                    <td align="left">QALY incremental</td>
                    <td align="center">
										</td>
                    <td align="center">1,46</td>
                    <td align="center">1,31</td>
                  </tr>
                  <tr>
                    <td align="left">Custo incremental (R$) por QALY</td>
                    <td align="center">
										</td>
                    <td align="center">41.123</td>
                    <td align="center">40.309</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN20">
                  <p>QALY: anos de vida ajustados por qualidade; CP: cuidado padr&#227;o; TM: telemedicina; STE: suporte telef&#244;nico estruturado.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
            <p>Admitindo um limiar de WTP de R$ 27.328-81.984/QALY, a an&#225;lise de custo-efetividade sugere que TM e STE possam ser op&#231;&#245;es de tratamento custo-efetivo para o manejo de pacientes com IC.</p>
          </sec>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Nosso estudo fornece uma estimativa inicial do custo de quatro doen&#231;as no Brasil. Ao analis&#225;-las ao mesmo tempo em uma estrutura comum, fomos capazes de identificar o impacto total e os impactos de cada doen&#231;a em rela&#231;&#227;o &#224;s demais. Observamos que, enquanto o IM apresenta significativos custos de cuidados agudos, n&#227;o tem significativos custos de cuidados informais como a IC ou a HTN. Ao contr&#225;rio, embora a IC n&#227;o tenha significativos custos de cuidados agudos como o IM, apresenta significativa perda de produtividade. Enquanto a HTN apresenta baixo custo de sa&#250;de por pessoa, tem um significativo custo total devido ao grande n&#250;mero de pessoas com a condi&#231;&#227;o. Nossa an&#225;lise demonstra que essas condi&#231;&#245;es podem apresentar um grande impacto na produtividade e no bem-estar, al&#233;m de seus custos no sistema de sa&#250;de, o que &#233; um importante achado a partir da perspectiva societ&#225;ria. Se os legisladores focarem apenas nos custos de sa&#250;de de uma condi&#231;&#227;o, ou no custo relativo do cuidado por pessoa, podem deixar passar o impacto maior que tal condi&#231;&#227;o exerce na economia, bem como seu verdadeiro custo ao serem considerados outros impactos fiscais.</p>
        <p>Embora o estudo tenha focado o uso de conjuntos de dados administrativos para custos de sa&#250;de, pois h&#225; maior probabilidade de refletirem a aloca&#231;&#227;o de custo por pagador, os pr&#243;prios conjuntos de dados podem n&#227;o refletir os reais custos para cada condi&#231;&#227;o. Por exemplo, a codifica&#231;&#227;o e o relato das condi&#231;&#245;es acham-se sujeitos ao julgamento individual dos cl&#237;nicos para a indica&#231;&#227;o da causa de base, da condi&#231;&#227;o ativa ou da condi&#231;&#227;o cr&#244;nica como a condi&#231;&#227;o prim&#225;ria, e tal escolha pode mudar o relato dos impactos atribu&#237;veis. Uma revis&#227;o sistem&#225;tica e meta-an&#225;lise de banco de dados administrativos para IC identificou que os conjuntos de dados n&#227;o capturam um quarto dos casos,<xref ref-type="bibr" rid="B27">27</xref> enquanto uma revis&#227;o sistem&#225;tica de dados m&#233;dicos eletr&#244;nicos para FA mostrou a exist&#234;ncia de foco desproporcional em dados de pacientes hospitalizados, sendo necess&#225;ria pesquisa adicional incorporando c&#243;digos de pacientes externos e achados eletrocardiogr&#225;ficos para identificar corretamente as apresenta&#231;&#245;es de FA.<xref ref-type="bibr" rid="B28">28</xref> Logo, enquanto os custos relatados refletem o atual julgamento cl&#237;nico e o relato administrativo, a aloca&#231;&#227;o de custo atribu&#237;da a cada condi&#231;&#227;o pode continuar a ser melhorada.</p>
        <p>Ao atribuir gravidade relativa &#224;s condi&#231;&#245;es, seu tratamento e impacto nas condi&#231;&#245;es relacionadas devem ser considerados. O tratamento de uma dessas condi&#231;&#245;es poderia aliviar o desenvolvimento futuro de outra, e detalhes das rela&#231;&#245;es entre as condi&#231;&#245;es ainda est&#227;o sendo estabelecidos. Por exemplo, enquanto a HTN &#233; considerada um fator de risco comum para doen&#231;as card&#237;acas, h&#225; evid&#234;ncia cada vez maior sugerindo a associa&#231;&#227;o entre FA e IM.<xref ref-type="bibr" rid="B29">29</xref> Logo, abordar a FA poderia aliviar futuros casos de IM e o custo correspondente a ele atribu&#237;do.</p>
        <p>A maior limita&#231;&#227;o deste estudo foi a ampla disponibilidade de dados. Tr&#234;s pressupostos principais na metodologia tiveram que ser estabelecidos, o que pode ter tido um impacto nos resultados. Primeiro, nossas estimativas de custos de sa&#250;de foram guiadas por estat&#237;sticas hospitalares relatadas para cada uma das condi&#231;&#245;es. Isso deve ser mais apropriado para condi&#231;&#245;es que requeiram significativo manejo de cuidado agudo (e.g. IM), mas pode sub-representar o verdadeiro custo das condi&#231;&#245;es com maior &#234;nfase no cuidado prim&#225;rio ou manejo farmacol&#243;gico, como a HTN. Segundo, comum a todas as estimativas de produtividade que usam uma abordagem de capital humano, a taxa de desemprego no Brasil pode ou n&#227;o ser suficientemente baixa para ficar sujeita a uma perda permanente de produtividade. A partir da perspectiva societ&#225;ria, uma perda de produtividade por doen&#231;a card&#237;aca s&#243; equivale a uma perda de produtividade para a economia se a taxa de desemprego n&#227;o aumenta de forma acelerada, de modo que qualquer redu&#231;&#227;o em horas trabalhadas devido a enfermidade n&#227;o possa ser reposta em longo prazo com a admiss&#227;o ou o aumento de horas de outros trabalhadores substitutos. Terceiro, embora TM e STE tenham mostrado efeitos ben&#233;ficos na redu&#231;&#227;o da mortalidade por todas as causas para pacientes de IC que receberam alta recentemente no estudo original,<xref ref-type="bibr" rid="B24">24</xref> tais resultados foram estatisticamente inconclusivos. Embora tal incerteza quanto &#224;s estimativas tenha sido avaliada na an&#225;lise de sensibilidade, essas estrat&#233;gias ter&#227;o que ser reexaminadas &#224; medida que surjam novas evid&#234;ncias.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Este estudo mostrou que, no Brasil, as doen&#231;as card&#237;acas exercem significativo impacto financeiro e no bem-estar, com um custo de R$ 56,2 bilh&#245;es apenas em 2015 para as quatro condi&#231;&#245;es. Preven&#231;&#227;o ou melhor manejo das doen&#231;as card&#237;acas poderia resultar em significativos benef&#237;cios para melhorar o bem-estar e preservar a economia. A TM e o STE s&#227;o mecanismos custo-efetivos para aprimorar o manejo da IC.</p>
        <p>Este estudo foi financiado pelo Grupo Novartis. Os autores s&#227;o os &#250;nicos respons&#225;veis pelo seu conte&#250;do.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo foi financiado pela Novartis Group.</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 fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
        </fn>
      </fn-group>
      <ack>
        <title>Agradecimentos</title>
        <p>Os autores de Deloitte Access Economics desenharam o estudo, coletaram dados, realizaram a an&#225;lise e esbo&#231;aram o manuscrito. Todos os autores leram, comentaram e aprovaram o manuscrito final. Esta pesquisa &#233; parte de um estudo maior da Am&#233;rica Latina, com identifica&#231;&#227;o de resultados espec&#237;ficos para alguns pa&#237;ses, como M&#233;xico, Chile, Peru, Venezuela, Col&#244;mbia, Equador, Panam&#225; e El Salvador. Os resultados do Brasil foram apresentados no Congresso Europeu ISPOR em Viena em novembro de 2016 e no Congresso Cardiovascular Mundial em junho de 2016.</p>
      </ack>
    </back>
  </sub-article>
</article>
