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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.1" specific-use="sps-1.7" xml:lang="en">
  <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">sgdRGdPBkh8CWk8Z7zdZRqy</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2018000400321</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2018005004103</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20180044</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Short-Term and Mid-Term Clinical Outcomes Following Hybrid Coronary Revascularization Versus Off-Pump Coronary Artery Bypass: A Meta-Analysis</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Dong</surname>
            <given-names>Li</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="fn" rid="fn1">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kang</surname>
            <given-names>Yi-kun</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="fn" rid="fn1">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>An</surname>
            <given-names>Xiang-guang</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <institution content-type="orgname">Capital Medical University</institution>
          <institution content-type="orgdiv1">Beijing Chaoyang Hospital</institution>
          <addr-line>
            <city>Beijng</city>
          </addr-line>
          <country country="CN">China</country>
          <institution content-type="original">Heart Center &amp; Beijing Key Laboratory of Hypertension - Beijing Chaoyang Hospital - Capital Medical University, Beijng - China</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Xiang-guang An</bold>, Heart Center &amp; Beijing Key Laboratory of Hypertension - Beijing Chaoyang Hospital - Capital Medical University, Beijng 100020, China. E-mail: <email>anxiangguang@sina.com</email>
				</corresp>
        <fn fn-type="equal" id="fn1">
          <label>*</label>
          <p>Contributed equally to this paper, and should be regarded as co-first authors</p>
        </fn>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research and Critical revision of the manuscript for intellectual content: Xiang-guang A; Acquisition of data, Analysis and interpretation of the data, Statistical analysis and Writing of the manuscript: Li D, Yi-kun K.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>19</day>
        <month>03</month>
        <year>2018</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>04</month>
        <year>2018</year>
      </pub-date>
      <volume>110</volume>
      <issue>4</issue>
      <fpage>321</fpage>
      <lpage>330</lpage>
      <history>
        <date date-type="received">
          <day>07</day>
          <month>08</month>
          <year>2017</year>
        </date>
        <date date-type="rev-recd">
          <day>22</day>
          <month>09</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>06</day>
          <month>10</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>Off-pump coronary artery bypass grafting (OPCAB) is one of the standard treatments for coronary artery disease (CAD) while hybrid coronary revascularization (HCR) represents an evolving revascularization strategy. However, the difference in outcomes between them remains unclear.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>We performed a meta-analysis to compare the short-term and mid-term outcomes of HCR versus OPCAB for the treatment of multivessel or left main CAD.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>We searched the PubMed, EMBASE, Web of Science and Cochrane databases to identify related studies and a routine meta-analysis was conducted.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Nine studies with 6121 patients were included in the analysis. There was no significant difference in short-term major adverse cardiac and cerebrovascular event (MACCE) rate (RR: 0.55, 95% CI: 0.30-1.03, p = 0.06) or mortality (RR: 0.51, 95% CI: 0.17-1.48, p = 0.22). HCR required less ventilator time (SMD: -0.36, 95% CI: -0.55- -0.16, p &lt; 0.001), ICU stay (SMD: -0.35, 95% CI: -0.58 - -0.13, p &lt; 0.01), hospital stay (SMD: -0.29, 95% CI: -0.50- -0.07, p &lt; 0.05) and blood transfusion rate (RR: 0.57, 95% CI: 0.49-0.67, p &lt; 0.001), but needed more operation time (SMD: 1.29, 95% CI: 0.54-2.05, p &lt; 0.001) and hospitalization costs (SMD: 1.06, 95% CI: 0.45-1.66, p &lt; 0.001). The HCR group had lower mid-term MACCE rate (RR: 0.49, 95% CI: 0.26-0.92, p &lt; 0.05) but higher rate in mid-term target vessel revascularization (TVR, RR: 2.20, 95% CI: 1.32-3.67, p &lt; 0.01).</p>
        </sec>
        <sec>
          <title>Conclusions:</title>
          <p>HCR had similar short-term mortality and morbidity comparing to OPCAB. HCR decreased the ventilator time, ICU stay, hospital stay, blood transfusion rate and increased operation time and hospitalization costs. HCR has a lower mid-term MACCE rate while OPCAB shows better in mid-term TVR.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Coronary Artery Disease/surgery</kwd>
        <kwd>Coronary Artery Bypass, Off-Pump</kwd>
        <kwd>Myocardial Revascularization/trends</kwd>
        <kwd>Meta-Analysis</kwd>
        <kwd>Database Bibliographic</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Surgical revascularization still plays an essential role in the treatment of coronary artery disease (CAD) even in the era of widely prevalent percutaneous coronary intervention (PCI). As the most classical and widespread procedure for revascularization, coronary artery bypass grafting (CABG) has been considered the gold standard therapy in the past decades.<xref ref-type="bibr" rid="B1">1</xref> In order to be safe and less disruptive, hybrid coronary revascularization (HCR) and off-pump coronary artery bypass grafting (OPCAB) which combines an off-pump technique with total arterial grafting. Recent years, more and more cardiac centers in the world have adopted OPCAB and HCR.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>It has been intensively discussed whether OPCAB is superior for CAD compared with on-pump CABG, but it remains uncertain. A recent randomized controlled trial (RCT) including 4752 patients found that the outcomes of death, stroke, myocardial infarction, renal failure or repeat revascularization at 5-year follow-up were similar among patients who underwent OPCAB or on-pump CABG.<xref ref-type="bibr" rid="B4">4</xref> Another research investigated 3445 patents with a 13-year follow-up and drew conclusions that both OPCAB and on-pump CABG were safe and effective, and no significant difference was observed between them.<xref ref-type="bibr" rid="B5">5</xref> However, a meta-analysis including 12 studies detected a lower rate of death and adverse effects after OPCAB compared with conventional CABG.<xref ref-type="bibr" rid="B6">6</xref> Generally speaking, OPCAB is considered as lower incidence of neurological complications (including stroke, cognitive decline, etc.),<xref ref-type="bibr" rid="B7">7</xref> in addition to a comparable less mortality and morbidity, particularly in high-risk groups and elderly patients.<xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref>
			</p>
      <p>HCR combines minimally invasive CABG and PCI, offering a relatively atraumatic therapy for multivessel CAD. HCR utilizes a left internal mammary artery (LIMA) graft to the left anterior descending (LAD) coronary artery with drug-eluting stents (DES) to non-LAD target coronary arteries. Several studies have proved the excellent postoperative survival (higher than 99%) and LIMA patency rates (higher than 95%) of HCR, suggesting HCR should be considered as an alternative approach for patients with multivessel CAD.<xref ref-type="bibr" rid="B10">10</xref> A study in France confirmed the feasibility and safety of HCR and also detected that HCR compared favorably to those with traditional CABG alone.<xref ref-type="bibr" rid="B11">11</xref> In addition, both of simultaneous and staged HCR were indicated to be efficient and feasible with favorable outcomes at more than 12-month follow-up.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> However, a 1-year clinical follow-up study angiographically showed a high rate of repeat revascularization after HCR.<xref ref-type="bibr" rid="B14">14</xref> In addition, a transient reduction in the antiplatelet effect of aspirin and clopidogrel was observed after HCR despite limited surgical trauma and off-pump technique.<xref ref-type="bibr" rid="B15">15</xref> Neither baseline platelet aggregation nor postoperatively increased platelet turnover and acute-phase response could explain it. Therefore, further research is badly needed.</p>
      <p>Currently, several comparative studies about the clinical outcomes of OPCAB and HCR are available. Nonetheless, the optimal surgical strategy remains disputable. In the present analysis, we sought to compare the short-term and mid-term clinical outcomes of HCR versus OPCAB for the treatment of multivessel or left main CAD with a pooled data.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Search strategy and selection criteria</title>
        <p>We searched four electronic bibliographic databases including PubMed, EMBASE, Web of Science and Cochrane by using following keywords with different combinations: &#8220;coronary artery disease&#8221;, &#8220;multivessel coronary artery disease&#8221;, &#8220;left main coronary artery disease&#8221;, &#8220;no-touch coronary artery bypass&#8221;, &#8220;off-pump coronary artery bypass&#8221;, &#8220;hybrid coronary revascularization&#8221;, &#8220;minimally invasive coronary artery bypass&#8221; and &#8220;percutaneous coronary intervention&#8221;. The searches were limited to human studies and English-language literatures only. The last search date was March 1, 2017.</p>
        <p>Inclusion criteria were: (1) RCTs, cohort studies or case-control trials (CCT) comparing the outcomes of HCR and OPCAB; (2) at least 15 participants in each group; (3) available to get complete data. In addition, exclusion criteria were: (1) duplicated papers that fail to provide supplementary information; (2) unfinished studies or unavailable data (3) studies with obvious defects in design or data statistics. Two researchers selected literatures and any disagreements were resolved through consensus.</p>
      </sec>
      <sec>
        <title>Data extraction and quality assessment</title>
        <p>For articles approved in the primary selection, two reviewers assessed the quality of studies and extract data independently. The CONSORT statement<xref ref-type="bibr" rid="B16">16</xref> and STROBE statement<xref ref-type="bibr" rid="B17">17</xref> were used to measure the quality of RCTs and observational studies, respectively. Low-quality studies should be excluded and any disagreements were resolved by consensus or judged by the senior author.</p>
        <p>Extracted information included: (1) characteristics of studies and patients; (2) basic management of HCR and OPCAB; (3) short-term (in-hospital or 30-day) and mid-term (3 months to 36 months) mortality, stroke and major adverse cardiac and cerebrovascular event (MACCE) which was defined as the incidence of all-cause death, stroke, myocardial infarction (MI) and target vessel revascularization (TVR); (4) in-hospital outcomes: operation time, ventilator time, ICU stay, hospital stay, blood transfusion rate, incidence of atrial fibrillation (AF) and hospitalization costs.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>We performed the analyses using RevMan 5.3 software (Cochrane Collaboration, Copenhagen, Denmark). Relative risk (RR) with 95% confidence interval (CI) was calculated for dichotomous variables and standardized mean difference (SMD) with 95% CI was calculated for continuous variables. Then <italic>Forest plots</italic> were presented graphically for all clinical outcomes. Statistical heterogeneity between studies was calculated using chi-squared test and the <italic>I</italic>-squared measure on a scale of 0-100% (less than 50% represented a low heterogeneity, 50%-75% indicated a moderate inconsistency and higher than 75% meant a large degree of heterogeneity). Fix-effect model was used in analysis with heterogeneity &lt; 50% while random-effect model was conducted with heterogeneity &#8805; 50%. In addition, publication bias of short-term (in-hospital or 30-day) MACCE rate was also assessed using funnel plot. Two-sided p value &lt; 0.05 was considered statistically significant.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Literature selection and characteristics of studies</title>
        <p>The process of literature selection for potentially eligible studies and exclusion reasons is illustrated using a flow diagram in <xref ref-type="fig" rid="f1">Figure 1</xref>. Initially, 1045 published articles were identified (455 from PubMed, 469 from EMBASE, 106 from Web of Science and 15 from Cochrane). Overall, 52 unduplicated English articles related to HCR and OPCAB were selected from these citations. Finally, nine observational studies with 6121 patients were included in the present analysis.<xref ref-type="bibr" rid="B18">18</xref><sup>-</sup><xref ref-type="bibr" rid="B26">26</xref>
				</p>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Flow diagram shows the process of literature selection.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0321-80044-gf01.jpg"/></fig>
        </p>
        <p>The basic characteristics of these studies are presented in <xref ref-type="table" rid="t1">Table 1</xref>. Among 6121 patients, 5418 (88.5%) subjects got OPCAB while 290 (4.7%) patients received staged HCR and 398 (6.7%) patients received simultaneous HCR. For those who underwent HCR, minimal invasive techniques such as endoscopic atraumatic coronary artery bypass (endo-ACAB), mini-sternotomy and mini-thoracotomy were utilized. Most of them received DES and a combination of aspirin and clopidogrel was applied as a preventive antiplatelet therapy. Short-term (in-hospital or 30-day) and mid-term clinical outcomes are shown in <xref ref-type="table" rid="t2">Table 2</xref>.</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Characteristics of the included studies</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">References</th>
                <th align="center" rowspan="2">Year</th>
                <th align="center" rowspan="2">Primary endpoint</th>
                <th align="center" rowspan="2">Follow-up</th>
                <th align="center" colspan="7" style="border-bottom-width:thin;border-bottom-style:solid">HCR</th>
                <th align="center" colspan="3" style="border-bottom-width:thin;border-bottom-style:solid">OPCAB</th>
              </tr>
              <tr>
                <th align="center">Number of patients</th>
                <th align="center">Mean age</th>
                <th align="center">Baseline LVEF (%)</th>
                <th align="center">Setting</th>
                <th align="center">Surgery type</th>
                <th align="center">Stents</th>
                <th align="center">Antiplatelet strategy</th>
                <th align="center">Number of patients</th>
                <th align="center">Mean age</th>
                <th align="center">Baseline LVEF (%)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Kon<xref ref-type="bibr" rid="B18">18</xref>
								</td>
                <td align="center">2008</td>
                <td align="center">In-hospital MACCE</td>
                <td align="center">1 year</td>
                <td align="center">15</td>
                <td align="center">61.0 &#177; 10.0</td>
                <td align="center">47.0 &#177; 14.0</td>
                <td align="center">Simultaneous</td>
                <td align="center">Smallthoracotomy</td>
                <td align="center">DES</td>
                <td align="center">Aspirin 325 mg, clopidogrel 300 mg</td>
                <td align="center">30</td>
                <td align="center">65.0 &#177; 10.0 </td>
                <td align="center">45.0 &#177; 14.0</td>
              </tr>
              <tr>
                <td align="left">Vassiliades<xref ref-type="bibr" rid="B19">19</xref>
								</td>
                <td align="center">2009</td>
                <td align="center">In-hospital mortality</td>
                <td align="center">1 year</td>
                <td align="center">91</td>
                <td align="center">64.7 &#177; 13.7</td>
                <td align="center">51.5 &#177; 9.4</td>
                <td align="center">Staged</td>
                <td align="center">Endo-ACAB</td>
                <td align="center">DES(85.8%)</td>
                <td align="center">Aspirin 81-162 mg, clopidogrel 75 mg</td>
                <td align="center">4175</td>
                <td align="center">62.8 &#177; 11.7</td>
                <td align="center">50.9 &#177; 12.7</td>
              </tr>
              <tr>
                <td align="left">Hu<xref ref-type="bibr" rid="B20">20</xref>
								</td>
                <td align="center">2010</td>
                <td align="center">In-hospital MACCE</td>
                <td align="center">Mean 18 months</td>
                <td align="center">104</td>
                <td align="center">61.8 &#177; 10.2</td>
                <td align="center">62.4 &#177; 6.9</td>
                <td align="center">Simultaneous</td>
                <td align="center">Ministernotomy</td>
                <td align="center">DES</td>
                <td align="center">Aspirin 100 mg, clopidogrel 300 mg</td>
                <td align="center">104</td>
                <td align="center">62.4 &#177; 8.0</td>
                <td align="center">63.4 &#177; 7.5</td>
              </tr>
              <tr>
                <td align="left">Halkos<xref ref-type="bibr" rid="B21">21</xref>
								</td>
                <td align="center">2011</td>
                <td align="center">In-hospital MACCE</td>
                <td align="center">Median 3.2 years</td>
                <td align="center">147</td>
                <td align="center">64.3 &#177; 12.8</td>
                <td align="center">54.6 &#177; 8.7</td>
                <td align="center">Staged</td>
                <td align="center">Endo-ACAB with robotic assistance</td>
                <td align="center">DES (mojority)</td>
                <td align="center">Clopidogrel 600 mg</td>
                <td align="center">588</td>
                <td align="center">64.3 &#177; 12.5</td>
                <td align="center">54.7 &#177; 8.7</td>
              </tr>
              <tr>
                <td align="left">Halkos<xref ref-type="bibr" rid="B22">22</xref>
								</td>
                <td align="center">2011</td>
                <td align="center">In-hospital and 30-day MACCE</td>
                <td align="center">Median 3.2 years</td>
                <td align="center">27</td>
                <td align="center">63.9 &#177; 13.7</td>
                <td align="center">56.6 &#177; 7.7</td>
                <td align="center">Staged</td>
                <td align="center">Mini-sternotomy, robotic assistance</td>
                <td align="center">DES(92.6%)</td>
                <td align="center">Clopidogrel 600 mg</td>
                <td align="center">81</td>
                <td align="center">63.9 &#177; 12.7</td>
                <td align="center">56.6 &#177; 7.6</td>
              </tr>
              <tr>
                <td align="left">Bachinsky<xref ref-type="bibr" rid="B23">23</xref>
								</td>
                <td align="center">2012</td>
                <td align="center">In-hospital and 30-day MACCE</td>
                <td align="center">30 days</td>
                <td align="center">25</td>
                <td align="center">63.2 &#177; 10.5</td>
                <td align="center">55.3 &#177; 10.4</td>
                <td align="center">Staged</td>
                <td align="center">Thoracotomy with robotic assistance</td>
                <td align="center">DES(71.0%)</td>
                <td align="center">Aspirin 325 mg, clopidogrel 600 mg</td>
                <td align="center">27</td>
                <td align="center">66.8 &#177; 10.7</td>
                <td align="center">51.5 &#177; 12.0</td>
              </tr>
              <tr>
                <td align="left">Zhou<xref ref-type="bibr" rid="B24">24</xref>
								</td>
                <td align="center">2013</td>
                <td align="center">In-hospital MACCE</td>
                <td align="center">30 days</td>
                <td align="center">141</td>
                <td align="center">62.0 &#177; 10.1</td>
                <td align="center">61.8 &#177; 6.9</td>
                <td align="center">Simultaneous</td>
                <td align="center">Mini-sternotomy</td>
                <td align="center">DES</td>
                <td align="center">Aspirin 100 mg, heparin 120 IU/kg</td>
                <td align="center">141</td>
                <td align="center">63.2 &#177; 8.5</td>
                <td align="center">60.1 &#177; 9.3</td>
              </tr>
              <tr>
                <td align="left">Harskamp<xref ref-type="bibr" rid="B25">25</xref>
								</td>
                <td align="center">2014</td>
                <td align="center">cTnI after 24h</td>
                <td align="center">1 year</td>
                <td align="center">33</td>
                <td align="center">65.0 &#177; 6.5</td>
                <td align="center">55.0 &#177; 7.5</td>
                <td align="center">Simultaneous</td>
                <td align="center">Mini-thoracotomy with robotic assistance</td>
                <td align="center">DES(75.8%)</td>
                <td align="center">Aspirin and clopidogrel</td>
                <td align="center">32</td>
                <td align="center">67.0 &#177; 7.0</td>
                <td align="center">55.0 &#177; 5.0</td>
              </tr>
              <tr>
                <td align="left">Song<xref ref-type="bibr" rid="B26">26</xref>
								</td>
                <td align="center">2016</td>
                <td align="center">In-hospital outcomes</td>
                <td align="center">Median 2.5 years</td>
                <td align="center">120</td>
                <td align="center">62.3 &#177; 9.4</td>
                <td align="center">63.9 &#177; 7.3</td>
                <td align="center">Simultaneous</td>
                <td align="center">Mini-sternotomy</td>
                <td align="center">DES(99.5%)</td>
                <td align="center">Aspirin 100 mg, clopidogrel 300 mg</td>
                <td align="center">240</td>
                <td align="center">62.8 &#177; 8.4</td>
                <td align="center">64.2 &#177; 6.9</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>MACCE: major adverse cardiac and cerebrovascular event, cTnI: cardiac troponin I, HCR: hybrid coronary revascularization, OPCAB: Off-pump coronary artery bypass grafting, LVEF: left ventricular ejection fraction, endo&#8209;ACAB: endoscopic atraumatic coronary artery bypass, DES: drug-eluting stent.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Short-term and mid-term clinical outcomes of the included studies</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">References</th>
                <th align="center" rowspan="2">Time of outcomes</th>
                <th align="center" colspan="6" style="border-bottom-width:thin;border-bottom-style:solid">HCR</th>
                <th align="center" colspan="6" style="border-bottom-width:thin;border-bottom-style:solid">OPCAB</th>
              </tr>
              <tr>
                <th align="center">Number of patients</th>
                <th align="center">MACCE</th>
                <th align="center">Death</th>
                <th align="center">Stroke</th>
                <th align="center">MI</th>
                <th align="center">TVR</th>
                <th align="center">Number of patients</th>
                <th align="center">MACCE</th>
                <th align="center">Death</th>
                <th align="center">Stroke</th>
                <th align="center">MI</th>
                <th align="center">TVR</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="2">Kon<xref ref-type="bibr" rid="B18">18</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">15</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">30</td>
                <td align="center">7</td>
                <td align="center">0</td>
                <td align="center">1</td>
                <td align="center">6</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="center">Mid-term</td>
                <td align="center">15</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">1</td>
                <td align="center">30</td>
                <td align="center">7</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Vassiliades<xref ref-type="bibr" rid="B19">19</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">91</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">4175</td>
                <td align="center">126</td>
                <td align="center">74</td>
                <td align="center">47</td>
                <td align="center">20</td>
                <td align="center">12</td>
              </tr>
              <tr>
                <td align="center">Mid-term</td>
                <td align="center">91</td>
                <td align="center">10</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">7</td>
                <td align="center">4175</td>
                <td align="center">--</td>
                <td align="center">230</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Hu<xref ref-type="bibr" rid="B20">20</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">104</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">104</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="center">Mid-term</td>
                <td align="center">104</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">1</td>
                <td align="center">104</td>
                <td align="center">10</td>
                <td align="center">1</td>
                <td align="center">5</td>
                <td align="center">0</td>
                <td align="center">3</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Halkos<xref ref-type="bibr" rid="B21">21</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">147</td>
                <td align="center">3</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">588</td>
                <td align="center">12</td>
                <td align="center">5</td>
                <td align="center">4</td>
                <td align="center">3</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="center">Mid-term</td>
                <td align="center">147</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">13</td>
                <td align="center">588</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">18</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Halkos<xref ref-type="bibr" rid="B22">22</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">27</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">81</td>
                <td align="center">4</td>
                <td align="center">3</td>
                <td align="center">0</td>
                <td align="center">2</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="center">Mid-term</td>
                <td align="center">27</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">2</td>
                <td align="center">81</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">--</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Bachinsky<xref ref-type="bibr" rid="B23">23</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">25</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">27</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="left">Zhou<xref ref-type="bibr" rid="B24">24</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">141</td>
                <td align="center">7</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">5</td>
                <td align="center">0</td>
                <td align="center">141</td>
                <td align="center">10</td>
                <td align="center">2</td>
                <td align="center">1</td>
                <td align="center">7</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="left" rowspan="2">Harskamp<xref ref-type="bibr" rid="B25">25</xref>
								</td>
                <td align="center">Short-term</td>
                <td align="center">33</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">32</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">0</td>
              </tr>
              <tr>
                <td align="center">Mid-term</td>
                <td align="center">33</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">2</td>
                <td align="center">32</td>
                <td align="center">2</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">1</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Song<xref ref-type="bibr" rid="B26">26</xref>
								</td>
                <td align="center">Mid-term</td>
                <td align="center">120</td>
                <td align="center">8</td>
                <td align="center">3</td>
                <td align="center">0</td>
                <td align="center">0</td>
                <td align="center">5</td>
                <td align="center">237</td>
                <td align="center">19</td>
                <td align="center">6</td>
                <td align="center">8</td>
                <td align="center">2</td>
                <td align="center">6</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>HCR: hybrid coronary revascularization, OPCAB: Off-pump coronary artery bypass grafting, MACCE: major adverse cardiac and cerebrovascular event, MI: myocardial infarction, TVR: target vessel revascularization.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Short-term outcomes</title>
        <p>As illustrated in <xref ref-type="table" rid="t3">Table 3</xref>, there was no significant difference in short-term MACCE rate (relative risk (RR): 0.55, 95% confidence interval (CI): 0.30-1.03, p = 0.06; p for heterogeneity = 0.85, I<sup>2</sup> = 0%) or mortality (RR: 0.51, 95% CI: 0.17-1.48, p = 0.22; p for heterogeneity = 0.99, I<sup>2</sup>= 0%) or stroke (RR: 0.93, 95% CI: 0.28-3.05, p = 0.90; p for heterogeneity = 1.00, I<sup>2</sup> = 0%) between the two groups. HCR required less ventilator time (standardized mean difference (SMD): -0.36, 95% CI: -0.55- -0.16, p &lt; 0.001), ICU stay (SMD: -0.35, 95% CI: -0.58- -0.13, p &lt; 0.01), hospital stay (SMD: -0.29, 95% CI: -0.50- -0.07, p &lt; 0.05) and blood transfusion rate (relative risk (RR): 0.57, 95% CI: 0.49-0.67, p &lt; 0.001), but needed more operation time (SMD: 1.29, 95% CI: 0.54-2.05, p &lt; 0.001) and hospitalization costs (SMD: 1.06, 95% CI: 0.45-1.66, p &lt; 0.001).</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Summary of results for short-term clinical outcomes of HCR versus OPCAB</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
              <col width="16%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Outcomes</th>
                <th align="center">Number of studies</th>
                <th align="center">Total numbers of patients</th>
                <th align="center">SMD or RR</th>
                <th align="center">95% CI</th>
                <th align="center">p value</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Short-term MACCE rate</td>
                <td align="center">8</td>
                <td align="center">5761</td>
                <td align="center">0.55</td>
                <td align="center">[0.30, 1.03]</td>
                <td align="center">0.06</td>
              </tr>
              <tr>
                <td align="left">Staged HCR</td>
                <td align="center">4</td>
                <td align="center">5161</td>
                <td align="center">0.58</td>
                <td align="center">[0.23, 1.47]</td>
                <td align="center">0.25</td>
              </tr>
              <tr>
                <td align="left">Simultaneous HCR</td>
                <td align="center">4</td>
                <td align="center">600</td>
                <td align="center">0.54</td>
                <td align="center">[0.23, 1.23]</td>
                <td align="center">0.14</td>
              </tr>
              <tr>
                <td align="left">Short-term mortality</td>
                <td align="center">8</td>
                <td align="center">5761</td>
                <td align="center">0.51</td>
                <td align="center">[0.17, 1.48]</td>
                <td align="center">0.22</td>
              </tr>
              <tr>
                <td align="left">Staged HCR</td>
                <td align="center">4</td>
                <td align="center">5161</td>
                <td align="center">0.46</td>
                <td align="center">[0.12, 1.73]</td>
                <td align="center">0.25</td>
              </tr>
              <tr>
                <td align="left">Simultaneous HCR</td>
                <td align="center">4</td>
                <td align="center">600</td>
                <td align="center">0.66</td>
                <td align="center">[0.11, 3.88]</td>
                <td align="center">0.64</td>
              </tr>
              <tr>
                <td align="left">Short-term stroke</td>
                <td align="center">8</td>
                <td align="center">5761</td>
                <td align="center">0.93</td>
                <td align="center">[0.28, 3.05]</td>
                <td align="center">0.90</td>
              </tr>
              <tr>
                <td align="left">Operation time</td>
                <td align="center">3</td>
                <td align="center">542</td>
                <td align="center">1.29</td>
                <td align="center">[0.54, 2.05]</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">Ventilator time</td>
                <td align="center">6</td>
                <td align="center">1861</td>
                <td align="center">-0.36</td>
                <td align="center">[-0.55, -0.16]</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">ICU stay</td>
                <td align="center">7</td>
                <td align="center">1913</td>
                <td align="center">-0.35</td>
                <td align="center">[-0.58, -0.13]</td>
                <td align="center">0.002</td>
              </tr>
              <tr>
                <td align="left">Hospital stay</td>
                <td align="center">7</td>
                <td align="center">1538</td>
                <td align="center">-0.29</td>
                <td align="center">[-0.50, -0.07]</td>
                <td align="center">0.01</td>
              </tr>
              <tr>
                <td align="left">Blood transfusion rate</td>
                <td align="center">6</td>
                <td align="center">1361</td>
                <td align="center">0.57</td>
                <td align="center">[0.49, 0.67]</td>
                <td align="center">&lt; 0.001</td>
              </tr>
              <tr>
                <td align="left">AF rate</td>
                <td align="center">7</td>
                <td align="center">1933</td>
                <td align="center">1.08</td>
                <td align="center">[0.83, 1.40]</td>
                <td align="center">0.56</td>
              </tr>
              <tr>
                <td align="left">Hospitalization costs</td>
                <td align="center">3</td>
                <td align="center">305</td>
                <td align="center">1.06</td>
                <td align="center">[0.45, 1.66]</td>
                <td align="center">&lt; 0.001</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>HCR: hybrid coronary revascularization, OPCAB: Off-pump coronary artery bypass grafting, MACCE: major adverse cardiac and cerebrovascular event, AF: atrial fibrillation, SMD: standardized mean difference, RR: relative risk, CI: confidence interval.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Subgroup analysis</title>
        <p><xref ref-type="table" rid="t3">Table 3</xref> also showed the subgroup analysis, which was performed by dividing the studies into staged-HCR group and simultaneous-HCR group. No statistical difference was observed in short-term MACCE rate or mortality in the two subgroups (<italic>P</italic> value in both subgroups &gt; 0.05).</p>
      </sec>
      <sec>
        <title>Mid-term outcomes</title>
        <p>The studies that contained mid-term outcomes were included in the analysis. As shown in <xref ref-type="fig" rid="f2">Figure 2</xref>, the HCR group had lower MACCE rate (RR: 0.49, 95% CI: 0.26-0.92, p &lt; 0.05, P for heterogeneity = 0.26, I<sup>2</sup> = 25%) but had higher rate in TVR (RR: 2.20, 95% CI: 1.32-3.67, p &lt; 0.01, P for heterogeneity = 0.46, I<sup>2</sup> = 0%) in mid-term follow. No significant difference in mid-term mortality was detected between the two groups (RR: 0.47, 95% CI: 0.17-1.32, p &lt; 0.01, P for heterogeneity = 0.34, I<sup>2</sup> = 7%).</p>
        <p>
          <fig id="f2">
            <label>Figure 2</label>
            <caption>
              <title>Meta-analysis shows the relative risk (RR) of mid-term MACCE rate, mortality and TVR. MACCE: major adverse cardiac and cerebrovascular event, TVR: target vessel revascularization, CI: confidence interval, HCR: hybrid coronary revascularization; OPCAB: off-pump coronary artery bypass grafting.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0321-80044-gf02.jpg"/></fig>
        </p>
      </sec>
      <sec>
        <title>Heterogeneity</title>
        <p>In the current analysis, no obvious heterogeneity was found between studies in either short-term or mid-term MACCE rate and mortality (p for heterogeneity &gt; 0.05, I<sup>2</sup>&lt; 50%). And subgroup analysis showed no heterogeneity (p for heterogeneity = 0.95, I<sup>2</sup> = 0%).</p>
      </sec>
      <sec>
        <title>Publication bias</title>
        <p>The funnel graph of short-term MACCE rate was established in <xref ref-type="fig" rid="f3">Figure 3</xref>, and there was no evident publication bias among all included studies by visual examination.</p>
        <p>
          <fig id="f3">
            <label>Figure 3</label>
            <caption>
              <title>Funnel plot shows the test for publication bias of short-term (in-hospital or 30-day) mortality and MACCE rate. MACCE: major adverse cardiac and cerebrovascular event, RR: relative risk, SE: standard error.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-110-04-0321-80044-gf03.jpg"/></fig>
        </p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>The present meta-analysis shows that HCR, compared with OPCAB, seems not to significantly improve short-term mortality and morbidity of postoperative complications for patients with CAD. These results are similar to previews research. Hu<xref ref-type="bibr" rid="B27">27</xref> first systematically compared the short-term clinical outcomes after HCR versus OPCAB for the treatment of multivessel or left main CAD, and most of the results were consistent with the current analysis. However, some differences between the two analyses should be also mentioned. We excluded one study<xref ref-type="bibr" rid="B28">28</xref> due to small sample size(less than 15 patients), outdated surgical procedures (8-10 cm thoracotomy incisions), different kinds of DES (cypher or taxus), uncertainty of baseline LVEF (not reported) and high heterogeneity in analysis. We also put three recent high-quality studies into pooled data so that all outcomes are updated. In addition, in the present study, we focus on postoperative complications and take stroke as a primary endpoint. Therefore, the present analysis is needed for a better elucidation of HCR and OPCAB.</p>
      <p>To our knowledge, this is the first meta-analysis comparing the mid-term clinical outcomes between HCR and OPCAB so far. Our data shows that HCR has a lower mid-term MACCE rate while OPCAB shows a better result in mid-term TVR. Moreover, no significant difference in mid-term mortality was detected between the two groups. Patients undergoing the hybrid procedure have relatively better mid-term clinical outcomes probably owing to reduced myocardial manipulation and activation of coagulation<xref ref-type="bibr" rid="B26">26</xref><sup>.</sup> It has been widely recognized that the dislodgement or rupture of atherosclerotic plaques during surgical aortic manipulation results in a major cause of stroke.<xref ref-type="bibr" rid="B29">29</xref> Since the aorta is more or less affected in the surgical procedure, it is still unclear whether OPCAB can decrease postoperative stroke rate compared with on-pump CABG. In contrast, grafting in HCR only involves LAD artery while other coronary arteries are treated by PCI. As a result, low rate of neurological complications becomes one of the main advantages of HCR. Although, in the present analysis we detect no significant difference of stroke rate between OPCAB and HCR in a short-term follow-up, which seems to be contradictory to some previous analyses.</p>
      <p>However, Song et al.<xref ref-type="bibr" rid="B26">26</xref> reported that more patients in OPCAB group suffer from stroke than HCR group in a 30-month follow-up, which indicates that the differences may be well recognized in a long-term follow-up. In recent years, technical advances in OPCAB utilize a no-touch technique to avoid aortic manipulation during grafting. A retrospective study showed that the OPCAB with no-touch technique could improve prognosis by minimizing the neurological complications and the morbidity.<xref ref-type="bibr" rid="B30">30</xref> Emmert et al.<xref ref-type="bibr" rid="B31">31</xref> also reported that the aortic no-touch OPCAB provided superior neurological outcomes than on-pump CABG and no-touch technique should be properly applied. Halbersma et al.<xref ref-type="bibr" rid="B32">32</xref> investigated the four-year clinical outcomes after OPCAB with no-touch technique and concluded that it was a safe and efficient choice for patients with multivessel or left main CAD. Compelling data have indicated that the combination of OPCAB and clampless strategies can reduce stroke risk. However, the major shortcoming of no-touch OPCAB is its greater technical requirement so that it is not applicable for every surgical team or every patient.<xref ref-type="bibr" rid="B33">33</xref> Nevertheless, further investigations should be still carried out to compare no-touch OPCAB and HCR.</p>
      <p>In the current analysis, neither staged HCR nor simultaneous HCR makes a difference to the short-term outcomes, which is consistent with former studies.<xref ref-type="bibr" rid="B27">27</xref> Commonly, there are three strategies for HCR: (1) performing LIMA-LAD grafting first and then followed by PCI, the interval varies from several hours to a few weeks; (2) vice versa; (3) combined LIMA-LAD grafting and PCI at the same time in a hybrid operative unit. The optimal sequence of LIMA-LAD grafting and PCI has been debated but still remains unclear. In fact, most centers choose their own surgical procedures mainly based on preferences of physicians, considerations of patients, economic issues and available resources. Although several studies have indicated that both simultaneous and staged HCR contribute to excellent results, most centers prefer to adopt the latter one with LIMA-LAD grafting performed first.<xref ref-type="bibr" rid="B34">34</xref> The CABG-first approach is recommended by the American College of Cardiology Foundation/American Heart Association<xref ref-type="bibr" rid="B35">35</xref> and it has some obvious advantages. It can reduce the overlapping from two different teams so that they can perform in their most familiar way and avoid to interacting with each other in operation room. Then antiplatelet and antithrombotic strategies can be well managed and adjusted according to physicians from different teams.<xref ref-type="bibr" rid="B36">36</xref> However, the disadvantages include that patients have to undergo at least two surgeries and need more time to recover. Moreover, hemorrhagic tendency and overload of kidneys also deserve significant attention. Currently, no study has compared the clinical outcomes of staged HCR and simultaneous HCR directly, so further research should be placed on it.</p>
      <p>In the present analysis, we also confirm that HCR apparently decreases the ventilator time, ICU stay, hospital stay and blood transfusion rate comparing to OPCAB. Although these items may not directly influence the main outcomes, they are also important criteria to judge a surgical procedure. Several reasons may account for these advantages of HCR. With the development of surgical procedures, endoscopic technique and mini incision are widely utilized in HCR to help patients ease suffering and recover sooner.<xref ref-type="bibr" rid="B37">37</xref> And retractor-stabilizer, such as robot, provides access that LIMA-LAD grafting can be performed with accuracy and precision with minimally invasive thoracotomy or sternotomy.<xref ref-type="bibr" rid="B38">38</xref> Practically, with the assistance of a surgical robot, it offers an excellent visual field and reduces operation time. However, some drawbacks of HCR also deserve our attention. Our study detects that the hybrid procedure required longer operation time and incurred much higher in-hospital costs than OPCAB. In Bachinsky`s study,<xref ref-type="bibr" rid="B23">23</xref> despite lower postoperative costs, the HCR group still needs more overall hospital costs owning to its higher procedural costs. Consequently, pros and cons of HCR should be weighed and considered carefully before operation.</p>
      <p>Some limitations of the present analysis should be also emphasized. Firstly, all included studies belong to observational studies and no single RCT has been conducted so far. Secondly, some included studies contain relatively small samples (fewer than 50 patients) and remain imbalance of patient number between groups so that deviation of results may inevitably exist. Thirdly, long-term patency is more convincing than short-term and mid-term outcomes, but very limited references were published with long-term follow-up so far. Finally, some uncontrolled factors may interfere with the current analysis. Variables like gender ratio and LVEF at baseline have not been adjusted. And diverse surgery procedures, stents (DES or bare stent) as well as antiplatelet strategies may disturb the accuracy of results too.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusions</title>
      <p>HCR shows similar results with OPCAB in short-term clinical outcomes. HCR decreases the ventilator time, ICU stay, hospital stay, blood transfusion rate and increases the operation time and hospitalization costs. Although repeated vessel revascularization is greater with HCR, it has a lower mid-term MACCE rate and could provide a safe and reproducible alternative for patients with multivessel CAD.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
      <fn 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>
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  <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>Resultados Cl&#237;nicos de Curto e M&#233;dio Prazo ap&#243;s Revasculariza&#231;&#227;o Coronariana H&#237;brida versus Revasculariza&#231;&#227;o Mioc&#225;rdica sem Circula&#231;&#227;o Extracorp&#243;rea: Uma Meta-An&#225;lise</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Dong</surname>
            <given-names>Li</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="fn" rid="fn2">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kang</surname>
            <given-names>Yi-kun</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="fn" rid="fn2">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>An</surname>
            <given-names>Xiang-guang</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <institution content-type="original">Heart Center &amp; Beijing Key Laboratory of Hypertension - Beijing Chaoyang Hospital - Capital Medical University, Beijng - China</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Xiang-guang An</bold>, Heart Center &amp; Beijing Key Laboratory of Hypertension - Beijing Chaoyang Hospital - Capital Medical University, Beijng 100020, China. E-mail: <email>anxiangguang@sina.com</email>
				</corresp>
        <fn fn-type="equal" id="fn2">
          <label>*</label>
          <p>Contribu&#237;ram igualmente para este artigo.</p>
        </fn>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Xiang-guang A; Obten&#231;&#227;o de dados, An&#225;lise e interpreta&#231;&#227;o dos dados, An&#225;lise estat&#237;stica e Reda&#231;&#227;o do manuscrito: Li D, Yi-kun K.</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>Fundamentos:</title>
          <p>A revasculariza&#231;&#227;o do mioc&#225;rdio sem circula&#231;&#227;o extracorp&#243;rea (CRM sem CEC) &#233; um dos tratamentos padr&#227;o para a doen&#231;a arterial coron&#225;ria (DAC), enquanto que a revasculariza&#231;&#227;o coron&#225;ria h&#237;brida (RCH) &#233; uma estrat&#233;gia de revasculariza&#231;&#227;o em evolu&#231;&#227;o. No entanto, a diferen&#231;a nos resultados entre eles ainda n&#227;o est&#225; clara.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Realizamos uma meta-an&#225;lise para comparar os resultados a curto e m&#233;dio prazo da RCH versus a CRM sem CEC para o tratamento de DAC de m&#250;ltiplos vasos ou art&#233;ria principal esquerda.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Pesquisamos as bases de dados PubMed, EMBASE, Web of Science e Cochrane para identificar estudos relacionados e realizamos uma meta-an&#225;lise de rotina.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Nove estudos com 6121 pacientes foram inclu&#237;dos na an&#225;lise. N&#227;o houve diferen&#231;a significativa na taxa de eventos card&#237;acos e cerebrovasculares adversos maiores de curto prazo (ECCAM) (RR de 0,55, IC de 95% 0,30-1,03, p = 0,06) ou mortalidade (RR: 0,51, IC 95%: 0,17-1,48, p = 0,22). A RCH requereu menos tempo de ventila&#231;&#227;o (DMP -0,36; IC de 95%: -0,16 -0,55-, p &lt; 0,001), tempo de UTI (DMP: -0,35, IC de 95%: -0,58- -0,13, p &lt; 0,01), estadia hospitalar (DMP: -0,29; IC de 95%: -0.50 - -0,07, p &lt; 0,05) e taxa de transfus&#227;o de sangue (RR: Cl 0,57, 95% de 0,49-0,67, p &lt; 0,001), mas necessitou mais tempo de cirurgia (DMP): 1,29, IC de 95% 0,54-2,05, p &lt; 0,001) e custos de hospitaliza&#231;&#227;o (DMP: 1,06, 95 %: 0,45-1,66, p &lt; 0,001). O grupa RCH tinha uma taxa mais baixa de ECCAM a m&#233;dio prazo (RR de 0,49, IC de 95% 0,26-0,92, p &lt; 0,05), mas uma taxa mais elevada a m&#233;dio prazo em revasculariza&#231;&#227;o de vaso alvo (RVA, RR: 2,20, IC 95%: 1,32). 3,67, p &lt; 0,01).</p>
        </sec>
        <sec>
          <title>Conclus&#245;es:</title>
          <p>A RCH teve mortalidade e morbidade semelhantes no curto prazo comparada ao CRM sem CEC. A RCH diminuiu o tempo de ventila&#231;&#227;o, a interna&#231;&#227;o na UTI, a interna&#231;&#227;o hospitalar, a taxa de transfus&#227;o de sangue e o aumento do tempo de opera&#231;&#227;o e os custos de hospitaliza&#231;&#227;o. A RCH tem uma taxa ECCAM mais baixa no m&#233;dio prazo, enquanto a CRM sem CEC se mostra melhor em RVA a m&#233;dio prazo.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Doen&#231;a da Art&#233;ria Coronariana/cirurgia</kwd>
        <kwd>Ponte de Art&#233;ria Coron&#225;ria sem Circula&#231;&#227;o Extracorp&#243;rea</kwd>
        <kwd>Revasculariza&#231;&#227;o Mioc&#225;rdica/tend&#234;ncias</kwd>
        <kwd>Metan&#225;lise</kwd>
        <kwd>Bases de Dados Bibliogr&#225;ficas</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A revasculariza&#231;&#227;o cir&#250;rgica continua a desempenhar um papel essencial no tratamento da doen&#231;a arterial coronariana (DAC), mesmo na &#233;poca em que a interven&#231;&#227;o coron&#225;ria percut&#226;nea (ICP) &#233; amplamente prevalente. Na medida que o procedimento mais cl&#225;ssico e generalizado para revasculariza&#231;&#227;o, o bypass coron&#225;rio (CABG), tem sido considerado a terapia padr&#227;o ouro nas d&#233;cadas passadas,<xref ref-type="bibr" rid="B1">1</xref> foram propostas por ser mais seguras e menos disruptivas, a revasculariza&#231;&#227;o coronariana h&#237;brida (RCH) e a revasculariza&#231;&#227;o do mioc&#225;rdio sem circula&#231;&#227;o extracorp&#243;rea (CRM sem CEC) a que combina uma t&#233;cnica CEC com enxerto arterial total. Nos &#250;ltimos anos, mais e mais centros card&#237;acos no mundo adotaram a CRM sem CEC e a RCH.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>Foi discutido intensamente se a CRM sem CEC &#233; superior para DAC em compara&#231;&#227;o com CRM sem CEC, mas ainda permanece incerto. Um estudo recente (RCT) controlado randomizado incluindo 4752 pacientes verificou que os resultados de morte, acidente vascular cerebral, infarto do mioc&#225;rdio, insufici&#234;ncia renal ou revasculariza&#231;&#227;o repetida ap&#243;s 5 anos de acompanhamento foram semelhantes entre os pacientes que foram submetidos a revasculariza&#231;&#227;o do mioc&#225;rdio sem ou com CEC.<xref ref-type="bibr" rid="B4">4</xref> Outra pesquisa investigou 3.445 pacientes com seguimento de 13 anos e concluiu que tanto a CRM sem CEC como a CRM com CEC eram seguras e eficazes, e n&#227;o foram observadas diferen&#231;as significativas entre elas.<xref ref-type="bibr" rid="B5">5</xref> No entanto, uma meta-an&#225;lise que incluiu 12 estudos detectou uma menor taxa de morte e efeitos adversos ap&#243;s a CRM sem CEC em compara&#231;&#227;o com a CRM convencional.<xref ref-type="bibr" rid="B6">6</xref> De um modo geral, a CRM sem CEC &#233; considerada como de menor incid&#234;ncia de complica&#231;&#245;es neurol&#243;gicas (incluindo acidente vascular cerebral, comprometimento cognitivo, etc.),<xref ref-type="bibr" rid="B7">7</xref> al&#233;m de um menor mortalidade e morbidade compar&#225;veis, particularmente em grupos de alto risco e pacientes idosos.<xref ref-type="bibr" rid="B8">8</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref> A RCH combina a revasculariza&#231;&#227;o mioc&#225;rdica minimamente invasiva e o ICP, oferecendo uma terapia relativamente n&#227;o traum&#225;tica para DAC de m&#250;ltiplos vasos. A RCH usa um enxerto de art&#233;ria mam&#225;ria interna esquerda (AMIE) na art&#233;ria coron&#225;ria descendente anterior (CDA) anterior com stents de libera&#231;&#227;o de f&#225;rmaco (DES) para art&#233;rias coron&#225;rias alvo n&#227;o CDA. V&#225;rios estudos demonstraram as excelentes taxas de sobreviv&#234;ncia p&#243;s-operat&#243;ria (mais de 99%) e as taxas de pat&#234;ncia AMIE (mais de 95%) de RCH, sugerindo que a RCH deve ser considerada como uma abordagem alternativa para pacientes com DAC multivaso.<xref ref-type="bibr" rid="B10">10</xref>
				</p>
        <p>Um estudo realizado na Fran&#231;a confirmou a viabilidade e a seguran&#231;a da RCH e tamb&#233;m constatou que a RCH se comparou favoravelmente com aqueles com CABG tradicional sozinho.<xref ref-type="bibr" rid="B11">11</xref> Al&#233;m disso, foi indicado que tanto a RCH simult&#226;nea como a estagiada eram eficientes e vi&#225;veis com resultados favor&#225;veis em um seguimento de 12 meses.<xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> No entanto, um estudo de acompanhamento cl&#237;nico de um ano mostrou uma taxa angiogr&#225;fica de revasculariza&#231;&#227;o repetida elevada ap&#243;s RCH.<xref ref-type="bibr" rid="B14">14</xref> Al&#233;m disso, observou-se uma redu&#231;&#227;o transit&#243;ria no efeito antiplaquet&#225;rio da aspirina e do clopidogrel ap&#243;s a RCH apesar do trauma cir&#250;rgico limitado e t&#233;cnica sem circula&#231;&#227;o extracorp&#243;rea.<xref ref-type="bibr" rid="B15">15</xref> Nem a agrega&#231;&#227;o plaquet&#225;ria no in&#237;cio nem o aumento p&#243;s-operat&#243;rio do turnover plaquet&#225;rio e a resposta &#224; fase aguda podem explic&#225;-lo. Portanto, &#233; necess&#225;ria uma investiga&#231;&#227;o mais aprofundada.</p>
        <p>Atualmente, v&#225;rios estudos comparativos sobre os resultados cl&#237;nicos do CRM sem CEC e RCH est&#227;o dispon&#237;veis. No entanto, a estrat&#233;gia cir&#250;rgica ideal continua discut&#237;vel. Na an&#225;lise atual, tentamos comparar os resultados cl&#237;nicos de curto e m&#233;dio prazo de RCH versus CRM sem CEC para o tratamento de DAC de m&#250;ltiplos vasos ou art&#233;ria coron&#225;ria esquerda principal utilizando dados agrupados.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Estrat&#233;gia de pesquisa e crit&#233;rios de sele&#231;&#227;o</title>
          <p>Pesquisamos quatro bancos de dados bibliogr&#225;ficos eletr&#244;nicos, incluindo PubMed, EMBASE, Web of Science e Cochrane, utilizando as seguintes palavras-chave com diferentes combina&#231;&#245;es: "doen&#231;a arterial coron&#225;ria", "doen&#231;a arterial coron&#225;ria multivaso" "doen&#231;a da art&#233;ria coron&#225;ria esquerda principal" "bypass da art&#233;ria coron&#225;ria <italic>no touch</italic>" &#8221;revasculariza&#231;&#227;o do mioc&#225;rdio sem circula&#231;&#227;o extracorp&#243;rea&#8220; "revasculariza&#231;&#227;o coron&#225;ria h&#237;brida'' &#8220;revasculariza&#231;&#227;o coron&#225;ria minimamente invasiva&#8221; e &#8220;interven&#231;&#227;o coron&#225;ria percut&#226;nea". As pesquisas foram limitadas a estudos humanos e &#224;s literaturas apenas em ingl&#234;s. A &#250;ltima data de pesquisa foi 1&#186; de mar&#231;o de 2017.</p>
          <p>Os crit&#233;rios de inclus&#227;o foram: (1) ECRs, estudos de coorte ou ensaios de casos e controles (ECC) que compararam os resultados de RCH e CRM sem CEC; (2) pelo menos 15 participantes em cada grupo; (3) dispon&#237;vel para obter dados completos. E os crit&#233;rios de exclus&#227;o foram: (1) documentos duplicados que n&#227;o forneciam informa&#231;&#245;es complementares; (2) estudos n&#227;o conclu&#237;dos ou dados n&#227;o dispon&#237;veis (3) estudos com defeitos &#243;bvios em estat&#237;sticas de projeto ou dados. Dois pesquisadores selecionaram a literatura e os desacordos foram resolvidos por consenso.</p>
        </sec>
        <sec>
          <title>Extra&#231;&#227;o de dados e avalia&#231;&#227;o de qualidade</title>
          <p>Para os artigos aprovados na sele&#231;&#227;o prim&#225;ria, dois revisores avaliaram a qualidade dos estudos e extra&#237;ram os dados de forma independente. A declara&#231;&#227;o CONSORT<xref ref-type="bibr" rid="B16">16</xref> e a declara&#231;&#227;o STROBE<xref ref-type="bibr" rid="B17">17</xref> foram utilizadas para medir a qualidade dos ECR e os estudos observacionais, respectivamente. Estudos de baixa qualidade deveriam ser exclu&#237;dos e qualquer desacordo resolvido por consenso ou julgado pelo autor principal.</p>
          <p>A informa&#231;&#227;o extra&#237;da incluiu: (1) caracter&#237;sticas dos estudos e dos pacientes; (2) manejo b&#225;sico de RCH e CRM sem CEC; (3) mortalidade a curto prazo (hospitalar ou 30 dias) e de m&#233;dio prazo (3 meses a 36 meses), acidente vascular cerebral e grande evento card&#237;aco e cerebrovascular adverso (ECCAM) que foi definido como a incid&#234;ncia de morte por todas as causas, acidente vascular cerebral, infarto do mioc&#225;rdio (IM) e revasculariza&#231;&#227;o do vaso alvo (RVA); (4) resultados hospitalares: tempo de opera&#231;&#227;o, tempo de ventila&#231;&#227;o, interna&#231;&#227;o na UTI, interna&#231;&#227;o hospitalar, taxa de transfus&#227;o de sangue, incid&#234;ncia de fibrila&#231;&#227;o atrial (FA) e custos de hospitaliza&#231;&#227;o.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Realizamos as an&#225;lises usando o software RevMan 5.3 (Cochrane Collaboration, Copenhagen, Dinamarca). O risco relativo (RR) foi calculado com um intervalo de confian&#231;a (IC) de 95% para as vari&#225;veis dicot&#244;micas e a diferen&#231;a de m&#233;dia padronizada (DMP) com IC 95% foi calculada para as vari&#225;veis cont&#237;nuas. Ent&#227;o, o <italic>Forest plot</italic> foi apresentado graficamente para todos os resultados cl&#237;nicos. A heterogeneidade estat&#237;stica entre os estudos foi calculada utilizando o teste de qui-quadrado e a medida de <italic>I</italic>-quadrado em uma escala de 0-100% (menos de 50% apresentaram baixa heterogeneidade, 50% -75% indicaram uma inconsist&#234;ncia moderada e mais do que 75% significaram um alto grau de heterogeneidade). Utilizamos o modelo de efeitos fixos na an&#225;lise com heterogeneidade &lt; 50% enquanto o modelo de efeitos aleat&#243;rios foi realizado com heterogeneidade &#8805; 50%. Al&#233;m disso, o vi&#233;s de publica&#231;&#227;o da taxa ECCAM no curto prazo (intrahospital&#225;rio ou 30 dias) tamb&#233;m foi avaliado usando um gr&#225;fico de funil. O valor <italic>P</italic> de dois lados &lt; 0,05 foi considerado estatisticamente significante.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <sec>
          <title>Sele&#231;&#227;o de literatura e caracter&#237;sticas dos estudos</title>
          <p>O processo de sele&#231;&#227;o de literatura para estudos potencialmente eleg&#237;veis e os motivos da exclus&#227;o s&#227;o ilustrados usando um fluxograma na <xref ref-type="fig" rid="f4">Figura 1</xref>. Inicialmente, foram identificados 1045 artigos publicados (455 de PubMed, 469 da EMBASE, 106 da Web of Science e 15 de Cochrane). Em geral, 52 artigos ingleses n&#227;o duplicados relacionados &#224;s RCH e CRM sem CEC foram selecionados a partir dessas cita&#231;&#245;es. Finalmente, foram inclu&#237;dos nove estudos observacionais com um total de 6121 pacientes na an&#225;lise presente.<xref ref-type="bibr" rid="B18">18</xref><sup>-</sup><xref ref-type="bibr" rid="B26">26</xref>
					</p>
          <p>
            <fig id="f4">
              <label>Figura 1</label>
              <caption>
                <title>O diagrama de fluxo mostra o processo de sele&#231;&#227;o da literatura.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-110-04-0321-80044-gf01-pt.jpg"/></fig>
          </p>
          <p>As caracter&#237;sticas b&#225;sicas desses estudos s&#227;o apresentadas na <xref ref-type="table" rid="t4">Tabela 1</xref>. Entre 6121 pacientes, 5418 (88,5%) indiv&#237;duos receberam CRM sem CEC, enquanto 290 (4,7%) pacientes receberam RCH estagiada e 398 (6,7%) pacientes receberam RCH simult&#226;nea. Para aqueles que foram submetidos a RCH, utilizaram-se t&#233;cnicas minimamente invasivas, como o bypass endosc&#243;pico n&#227;o traum&#225;tico da art&#233;ria coron&#225;ria (endo-ACAB), mini-esternotomia e mini-toracotomia. A maioria deles recebeu DES e uma combina&#231;&#227;o de aspirina e clopidogrel foi aplicada como terapia preventiva antiplaquet&#225;ria. Os resultados cl&#237;nicos de curto prazo (intrahospital&#225;rio ou 30 dias) e de m&#233;dio prazo s&#227;o apresentados na <xref ref-type="table" rid="t5">Tabela 2</xref>.</p>
          <table-wrap id="t4">
            <label>Tabela 1</label>
            <caption>
              <title>Caracter&#237;sticas dos estudos inclu&#237;dos</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" rowspan="2">Refer&#234;ncias</th>
                  <th align="center" rowspan="2">Ano</th>
                  <th align="center" rowspan="2">Par&#226;metro final</th>
                  <th align="center" rowspan="2">Seguimento</th>
                  <th align="center" colspan="7" style="border-bottom-width:thin;border-bottom-style:solid">RCH</th>
                  <th align="center" colspan="3" style="border-bottom-width:thin;border-bottom-style:solid">CRM sem CEC</th>
                </tr>
                <tr>
                  <th align="center">N&#250;mero de pacientes</th>
                  <th align="center">Idade m&#233;dia</th>
                  <th align="center">LVEF (%)Basal</th>
                  <th align="center">Configura&#231;&#227;o</th>
                  <th align="center">Tipo de cirurgia</th>
                  <th align="center">Stents</th>
                  <th align="center">Estrat&#233;gia antiplaquet&#225;ria</th>
                  <th align="center">N&#250;mero de pacientes</th>
                  <th align="center">Idade m&#233;dia</th>
                  <th align="center">FEVE (%) Basal</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Kon<xref ref-type="bibr" rid="B18">18</xref>
									</td>
                  <td align="center">2008</td>
                  <td align="center">Intrahospital&#225;rio ECCAM</td>
                  <td align="center">1 ano</td>
                  <td align="center">15</td>
                  <td align="center">61.0 &#177; 10.0</td>
                  <td align="center">47.0 &#177; 14.0</td>
                  <td align="center">Simult&#226;nea</td>
                  <td align="center">Pequenatoracotomia</td>
                  <td align="center">DES</td>
                  <td align="center">Aspirina 325 mg, clopidogrel 300 mg</td>
                  <td align="center">30</td>
                  <td align="center">65.0 &#177; 10.0 </td>
                  <td align="center">45.0 &#177; 14.0</td>
                </tr>
                <tr>
                  <td align="left">Vassiliades<xref ref-type="bibr" rid="B19">19</xref>
									</td>
                  <td align="center">2009</td>
                  <td align="center">Intrahospital&#225;rio mortalidade</td>
                  <td align="center">1 ano</td>
                  <td align="center">91</td>
                  <td align="center">64.7 &#177; 13.7</td>
                  <td align="center">51.5 &#177; 9.4</td>
                  <td align="center">Estagiada</td>
                  <td align="center">Endo-ACAB</td>
                  <td align="center">DES(85.8%)</td>
                  <td align="center">Aspirina 81-162 mg, clopidogrel 75 mg</td>
                  <td align="center">4175</td>
                  <td align="center">62.8 &#177; 11.7</td>
                  <td align="center">50.9 &#177; 12.7</td>
                </tr>
                <tr>
                  <td align="left">Hu<xref ref-type="bibr" rid="B20">20</xref>
									</td>
                  <td align="center">2010</td>
                  <td align="center">Intrahospital&#225;rio ECCAM</td>
                  <td align="center">M&#233;dia 18 meses</td>
                  <td align="center">104</td>
                  <td align="center">61.8 &#177; 10.2</td>
                  <td align="center">62.4 &#177; 6.9</td>
                  <td align="center">Simult&#226;nea</td>
                  <td align="center">Miniesternotomia</td>
                  <td align="center">DES</td>
                  <td align="center">Aspirina 100 mg, clopidogrel 300 mg</td>
                  <td align="center">104</td>
                  <td align="center">62.4 &#177; 8.0</td>
                  <td align="center">63.4 &#177; 7.5</td>
                </tr>
                <tr>
                  <td align="left">Halkos<xref ref-type="bibr" rid="B21">21</xref>
									</td>
                  <td align="center">2011</td>
                  <td align="center">Intrahospital&#225;rio ECCAM</td>
                  <td align="center">Mediana 3.2 anos</td>
                  <td align="center">147</td>
                  <td align="center">64.3 &#177; 12.8</td>
                  <td align="center">54.6 &#177; 8.7</td>
                  <td align="center">Estagiada</td>
                  <td align="center">Endo-ACAB com assist&#234;ncia rob&#243;tica</td>
                  <td align="center">DES (mojority)</td>
                  <td align="center">Clopidogrel 600 mg</td>
                  <td align="center">588</td>
                  <td align="center">64.3 &#177; 12.5</td>
                  <td align="center">54.7 &#177; 8.7</td>
                </tr>
                <tr>
                  <td align="left">Halkos<xref ref-type="bibr" rid="B22">22</xref>
									</td>
                  <td align="center">2011</td>
                  <td align="center">Intrahospital&#225;rio y 30-dias ECCAM</td>
                  <td align="center">Mediana 3.2 anos</td>
                  <td align="center">27</td>
                  <td align="center">63.9 &#177; 13.7</td>
                  <td align="center">56.6 &#177; 7.7</td>
                  <td align="center">Estagiada</td>
                  <td align="center">Miniesternotomia, assist&#234;ncia rob&#243;tica</td>
                  <td align="center">DES(92.6%)</td>
                  <td align="center">Clopidogrel 600 mg</td>
                  <td align="center">81</td>
                  <td align="center">63.9 &#177; 12.7</td>
                  <td align="center">56.6 &#177; 7.6</td>
                </tr>
                <tr>
                  <td align="left">Bachinsky<xref ref-type="bibr" rid="B23">23</xref>
									</td>
                  <td align="center">2012</td>
                  <td align="center">Intrahospital&#225;rio y 30-dia ECCAM</td>
                  <td align="center">30 dias</td>
                  <td align="center">25</td>
                  <td align="center">63.2 &#177; 10.5</td>
                  <td align="center">55.3 &#177; 10.4</td>
                  <td align="center">Estagiada</td>
                  <td align="center">Toracotomia com assist&#234;ncia rob&#243;tica</td>
                  <td align="center">DES(71.0%)</td>
                  <td align="center">Aspirina 325 mg, clopidogrel 600 mg</td>
                  <td align="center">27</td>
                  <td align="center">66.8 &#177; 10.7</td>
                  <td align="center">51.5 &#177; 12.0</td>
                </tr>
                <tr>
                  <td align="left">Zhou<xref ref-type="bibr" rid="B24">24</xref>
									</td>
                  <td align="center">2013</td>
                  <td align="center">Intrahospital&#225;rio ECCAM</td>
                  <td align="center">30 dias</td>
                  <td align="center">141</td>
                  <td align="center">62.0 &#177; 10.1</td>
                  <td align="center">61.8 &#177; 6.9</td>
                  <td align="center">Simult&#226;nea</td>
                  <td align="center">Miniesternotomia</td>
                  <td align="center">DES</td>
                  <td align="center">Aspirina 100 mg, heparin 120 IU/kg</td>
                  <td align="center">141</td>
                  <td align="center">63.2 &#177; 8.5</td>
                  <td align="center">60.1 &#177; 9.3</td>
                </tr>
                <tr>
                  <td align="left">Harskamp<xref ref-type="bibr" rid="B25">25</xref>
									</td>
                  <td align="center">2014</td>
                  <td align="center">cTnI depois 24h</td>
                  <td align="center">1 ano</td>
                  <td align="center">33</td>
                  <td align="center">65.0 &#177; 6.5</td>
                  <td align="center">55.0 &#177; 7.5</td>
                  <td align="center">Simult&#226;nea</td>
                  <td align="center">Minitoracotomia com assist&#234;ncia rob&#243;tica</td>
                  <td align="center">DES(75.8%)</td>
                  <td align="center">Aspirina y clopidogrel</td>
                  <td align="center">32</td>
                  <td align="center">67.0 &#177; 7.0</td>
                  <td align="center">55.0 &#177; 5.0</td>
                </tr>
                <tr>
                  <td align="left">Song<xref ref-type="bibr" rid="B26">26</xref>
									</td>
                  <td align="center">2016</td>
                  <td align="center">Intrahospital&#225;rio resultados</td>
                  <td align="center">Mediana 2.5 anos</td>
                  <td align="center">120</td>
                  <td align="center">62.3 &#177; 9.4</td>
                  <td align="center">63.9 &#177; 7.3</td>
                  <td align="center">Simult&#226;nea</td>
                  <td align="center">Miniesternotomia</td>
                  <td align="center">DES(99.5%)</td>
                  <td align="center">Aspirina 100 mg, clopidogrel 300 mg</td>
                  <td align="center">240</td>
                  <td align="center">62.8 &#177; 8.4</td>
                  <td align="center">64.2 &#177; 6.9</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN4">
                <p>ECCAM: evento adverso card&#237;aco e cerebrovascular adverso maior, cTnI: troponina card&#237;aca I, RCH: revasculariza&#231;&#227;o coronariana h&#237;brida, CRM sem CEC: cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica sem circula&#231;&#227;o extracorp&#243;rea, FEVE: fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda, endo-ACAB: bypass endosc&#243;pico da art&#233;ria coron&#225;ria n&#227;o traum&#225;tico, DES: stent eluente de drogas</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t5">
            <label>Tabela 2</label>
            <caption>
              <title>Resultados cl&#237;nicos a curto prazo y m&#233;dio prazo dos estudos inclu&#237;dos</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" rowspan="2">Refer&#234;ncias</th>
                  <th align="center" rowspan="2">Tempo dos resultados</th>
                  <th align="center" colspan="6" style="border-bottom-width:thin;border-bottom-style:solid">RCH</th>
                  <th align="center" colspan="6" style="border-bottom-width:thin;border-bottom-style:solid">CRM sem CEC</th>
                </tr>
                <tr>
                  <th align="center">N&#250;mero de pacientes</th>
                  <th align="center">ECCAM</th>
                  <th align="center">Morte</th>
                  <th align="center">AVC</th>
                  <th align="center">IM</th>
                  <th align="center">RVA</th>
                  <th align="center">N&#250;mero de pacientes</th>
                  <th align="center">ECCAM</th>
                  <th align="center">Morte</th>
                  <th align="center">AVC</th>
                  <th align="center">IM</th>
                  <th align="center">RVA</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left" rowspan="2">Kon<xref ref-type="bibr" rid="B18">18</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">15</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">30</td>
                  <td align="center">7</td>
                  <td align="center">0</td>
                  <td align="center">1</td>
                  <td align="center">6</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="center">M&#233;dio prazo</td>
                  <td align="center">15</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">1</td>
                  <td align="center">30</td>
                  <td align="center">7</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Vassiliades<xref ref-type="bibr" rid="B19">19</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">91</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">4175</td>
                  <td align="center">126</td>
                  <td align="center">74</td>
                  <td align="center">47</td>
                  <td align="center">20</td>
                  <td align="center">12</td>
                </tr>
                <tr>
                  <td align="center">M&#233;dio prazo</td>
                  <td align="center">91</td>
                  <td align="center">10</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">7</td>
                  <td align="center">4175</td>
                  <td align="center">--</td>
                  <td align="center">230</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Hu<xref ref-type="bibr" rid="B20">20</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">104</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">104</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="center">M&#233;dio prazo</td>
                  <td align="center">104</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">1</td>
                  <td align="center">104</td>
                  <td align="center">10</td>
                  <td align="center">1</td>
                  <td align="center">5</td>
                  <td align="center">0</td>
                  <td align="center">3</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Halkos<xref ref-type="bibr" rid="B21">21</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">147</td>
                  <td align="center">3</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">588</td>
                  <td align="center">12</td>
                  <td align="center">5</td>
                  <td align="center">4</td>
                  <td align="center">3</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="center">M&#233;dio prazo</td>
                  <td align="center">147</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">13</td>
                  <td align="center">588</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">18</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Halkos<xref ref-type="bibr" rid="B22">22</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">27</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">81</td>
                  <td align="center">4</td>
                  <td align="center">3</td>
                  <td align="center">0</td>
                  <td align="center">2</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="center">M&#233;dio prazo</td>
                  <td align="center">27</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">2</td>
                  <td align="center">81</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">--</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Bachinsky<xref ref-type="bibr" rid="B23">23</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">25</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">27</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="left">Zhou<xref ref-type="bibr" rid="B24">24</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">141</td>
                  <td align="center">7</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">5</td>
                  <td align="center">0</td>
                  <td align="center">141</td>
                  <td align="center">10</td>
                  <td align="center">2</td>
                  <td align="center">1</td>
                  <td align="center">7</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="left" rowspan="2">Harskamp<xref ref-type="bibr" rid="B25">25</xref>
									</td>
                  <td align="center">Curto prazo</td>
                  <td align="center">33</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">32</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                </tr>
                <tr>
                  <td align="center">M&#233;dio prazo</td>
                  <td align="center">33</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">2</td>
                  <td align="center">32</td>
                  <td align="center">2</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Song<xref ref-type="bibr" rid="B26">26</xref>
									</td>
                  <td align="center">M&#233;dio prazo</td>
                  <td align="center">120</td>
                  <td align="center">8</td>
                  <td align="center">3</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">5</td>
                  <td align="center">237</td>
                  <td align="center">19</td>
                  <td align="center">6</td>
                  <td align="center">8</td>
                  <td align="center">2</td>
                  <td align="center">6</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN5">
                <p>RCH: revasculariza&#231;&#227;o coronariana h&#237;brida CRM sem CEC: cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica sem circula&#231;&#227;o extracorp&#243;rea, ECCAM: evento cerebrovascular card&#237;aco e adverso maior, IM: infarto do mioc&#225;rdio, RVA: revasculariza&#231;&#227;o do vaso alvo.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Resultados de curto prazo</title>
          <p>Conforme ilustrado na <xref ref-type="table" rid="t6">Tabela 3</xref>, n&#227;o houve diferen&#231;as significativas na taxa de ECCAM no curto prazo (risco relativo (RR): 0,55, intervalo de confian&#231;a de 95% (IC): 0,30-1,03, p = 0,06, p para heterogeneidade = 0,85, I<sup>2</sup> = 0%) ou mortalidade (RR: 0,51, IC 95%: 0,17-1,48, p = 0,22, p para heterogeneidade = 0,99, I<sup>2</sup> = 0%) ou acidente vascular cerebral (RR: 0,93, IC 95%: 0,28-3,05, p = 0,90, p para heterogeneidade = 1,00, I<sup>2</sup> = 0%) entre os dois grupos. RCH exigiu menos tempo de ventila&#231;&#227;o (diferen&#231;a de m&#233;dia padronizada (DMP): -0,36, IC 95%: -0,55- -0,16, p &lt; 0,001), perman&#234;ncia na UTI (DMP: -0, 35, IC 95%: -0,58- -0,13, p &lt; 0,01), interna&#231;&#227;o hospitalar (DMP: -0,29, IC 95%: -0,50 - -0,07, p &lt; 0,05) e taxa de transfus&#227;o de sangue (risco relativo (RR): 0,57, IC 95%: 0,49-0,67, p &lt; 0,001), mas necessitaram mais tempo de opera&#231;&#227;o (DMP: 1,29, IC 95%: 0,54-2,05, p &lt; 0,001) e custos de hospitaliza&#231;&#227;o (DMP: 1,06, IC 95%: 0,45-1,66, p &lt; 0,001).</p>
          <table-wrap id="t6">
            <label>Tabela 3</label>
            <caption>
              <title>Resumo de resultados cl&#237;nicos a curto prazo resultados de RCH versus CRM sem CEC</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
                <col width="16%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Resultados</th>
                  <th align="center">N&#250;mero de estudos</th>
                  <th align="center">N&#250;mero total de pacientes</th>
                  <th align="center">DMP ou RR </th>
                  <th align="center">95% CI</th>
                  <th align="center">Valor de p</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Taxa a curto prazo ECCAM</td>
                  <td align="center">8</td>
                  <td align="center">5761</td>
                  <td align="center">0.55</td>
                  <td align="center">[0.30, 1.03]</td>
                  <td align="center">0.06</td>
                </tr>
                <tr>
                  <td align="left">RCH estagiada</td>
                  <td align="center">4</td>
                  <td align="center">5161</td>
                  <td align="center">0.58</td>
                  <td align="center">[0.23, 1.47]</td>
                  <td align="center">0.25</td>
                </tr>
                <tr>
                  <td align="left">RCH simult&#226;nea</td>
                  <td align="center">4</td>
                  <td align="center">600</td>
                  <td align="center">0.54</td>
                  <td align="center">[0.23, 1.23]</td>
                  <td align="center">0.14</td>
                </tr>
                <tr>
                  <td align="left">Mortalidade a curto prazo</td>
                  <td align="center">8</td>
                  <td align="center">5761</td>
                  <td align="center">0.51</td>
                  <td align="center">[0.17, 1.48]</td>
                  <td align="center">0.22</td>
                </tr>
                <tr>
                  <td align="left">RCH estagiada</td>
                  <td align="center">4</td>
                  <td align="center">5161</td>
                  <td align="center">0.46</td>
                  <td align="center">[0.12, 1.73]</td>
                  <td align="center">0.25</td>
                </tr>
                <tr>
                  <td align="left">RCH simult&#226;nea</td>
                  <td align="center">4</td>
                  <td align="center">600</td>
                  <td align="center">0.66</td>
                  <td align="center">[0.11, 3.88]</td>
                  <td align="center">0.64</td>
                </tr>
                <tr>
                  <td align="left">AVC a curto prazo</td>
                  <td align="center">8</td>
                  <td align="center">5761</td>
                  <td align="center">0.93</td>
                  <td align="center">[0.28, 3.05]</td>
                  <td align="center">0.90</td>
                </tr>
                <tr>
                  <td align="left">Tempo de opera&#231;&#227;o</td>
                  <td align="center">3</td>
                  <td align="center">542</td>
                  <td align="center">1.29</td>
                  <td align="center">[0.54, 2.05]</td>
                  <td align="center">&lt; 0.001</td>
                </tr>
                <tr>
                  <td align="left">Tempo de ventila&#231;&#227;o</td>
                  <td align="center">6</td>
                  <td align="center">1861</td>
                  <td align="center">-0.36</td>
                  <td align="center">[-0.55, -0.16]</td>
                  <td align="center">&lt; 0.001</td>
                </tr>
                <tr>
                  <td align="left">Tempo na UTI</td>
                  <td align="center">7</td>
                  <td align="center">1913</td>
                  <td align="center">-0.35</td>
                  <td align="center">[-0.58, -0.13]</td>
                  <td align="center">0.002</td>
                </tr>
                <tr>
                  <td align="left">Tempo no Hospital</td>
                  <td align="center">7</td>
                  <td align="center">1538</td>
                  <td align="center">-0.29</td>
                  <td align="center">[-0.50, -0.07]</td>
                  <td align="center">0.01</td>
                </tr>
                <tr>
                  <td align="left">Taxa de transfus&#227;o</td>
                  <td align="center">6</td>
                  <td align="center">1361</td>
                  <td align="center">0.57</td>
                  <td align="center">[0.49, 0.67]</td>
                  <td align="center">&lt; 0.001</td>
                </tr>
                <tr>
                  <td align="left">Taxa fibrila&#231;&#227;o atrial</td>
                  <td align="center">7</td>
                  <td align="center">1933</td>
                  <td align="center">1.08</td>
                  <td align="center">[0.83, 1.40]</td>
                  <td align="center">0.56</td>
                </tr>
                <tr>
                  <td align="left">Custo hospitaliza&#231;&#227;o</td>
                  <td align="center">3</td>
                  <td align="center">305</td>
                  <td align="center">1.06</td>
                  <td align="center">[0.45, 1.66]</td>
                  <td align="center">&lt; 0.001</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN6">
                <p>RCH: revasculariza&#231;&#227;o coronariana h&#237;brida, CRM sem CEC: cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica sem circula&#231;&#227;o extracorp&#243;rea, ECCAM: evento adverso card&#237;aco e cerebrovascular adverso maior, FA: fibrila&#231;&#227;o atrial, DMP: diferen&#231;a de m&#233;dia padronizada, RR: risco relativo, IC: intervalo de confian&#231;a.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>An&#225;lise de subgrupos</title>
          <p>A <xref ref-type="table" rid="t6">Tabela 3</xref> tamb&#233;m mostrou a an&#225;lise do subgrupo, que foi realizada dividindo os estudos no grupo RCH estagiada e no grupo RCH simult&#226;nea. N&#227;o houve diferen&#231;a estat&#237;stica na taxa de ECCAM a curto prazo ou na mortalidade nos dois subgrupos (valor de p em ambos subgrupos &gt; 0,05).</p>
        </sec>
        <sec>
          <title>Resultados a m&#233;dio prazo</title>
          <p>Os estudos que continham resultados de m&#233;dio prazo foram inclu&#237;dos na an&#225;lise. Conforme mostrado na <xref ref-type="fig" rid="f5">Figura 2</xref>, o grupo RCH apresentou uma menor taxa de ECCAM (RR: 0,49, IC 95%: 0,26-0,92, p &lt; 0,05, p para heterogeneidade = 0,26, I<sup>2</sup> = 25%), mas teve uma taxa maior em RVA (RR: 2,20, IC 95%: 1,32-3,67, p &lt; 0,01, p para heterogeneidade = 0,46, I<sup>2</sup> = 0%) no m&#233;dio prazo. N&#227;o foram detectadas diferen&#231;as significativas na mortalidade a m&#233;dio prazo entre os dois grupos (RR: 0,47, IC 95%: 0,17-1,32, p &lt; 0,01, p para heterogeneidade = 0,34, I<sup>2</sup> = 7%).</p>
          <p>
            <fig id="f5">
              <label>Figura 2</label>
              <caption>
                <title>A meta-an&#225;lise mostra o risco relativo (RR) da taxa de m&#233;dio prazo do ECCAM, mortalidade e RVA. ECCAM: evento card&#237;aco e cerebrovascular adverso maior, RVA: revasculariza&#231;&#227;o do vaso alvo, IC: intervalo de confian&#231;a, RCH: revasculariza&#231;&#227;o coronariana h&#237;brida; CRM sem CEC: cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica sem circula&#231;&#227;o extracorp&#243;rea.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-110-04-0321-80044-gf02-pt.jpg"/></fig>
          </p>
        </sec>
        <sec>
          <title>Heterogeneidade</title>
          <p>Na an&#225;lise atual, nenhuma heterogeneidade &#243;bvia foi encontrada entre os estudos na taxa de ECCAM no curto ou m&#233;dio prazo e na mortalidade (p para heterogeneidade &gt; 0,05, I<sup>2</sup>&lt; 50%). E a an&#225;lise do subgrupo tamb&#233;m n&#227;o mostrou heterogeneidade (p para heterogeneidade = 0,95, I<sup>2</sup> = 0%).</p>
        </sec>
        <sec>
          <title>Vi&#233;s de publica&#231;&#227;o</title>
          <p>O gr&#225;fico do funil da taxa ECCAM no curto prazo foi estabelecido na <xref ref-type="fig" rid="f6">Figura 3</xref>, e n&#227;o houve um vi&#233;s de publica&#231;&#227;o evidente entre todos os estudos inclu&#237;dos por exame visual.</p>
          <p>
            <fig id="f6">
              <label>Figura 3</label>
              <caption>
                <title>O gr&#225;fico de funil mostra o teste de vi&#233;s de publica&#231;&#227;o de mortalidade a curto prazo (no hospital ou 30 dias) e a taxa de ECCAM. ECCAM: evento card&#237;aco e cerebrovascular adverso maior, RR: risco relativo, SE: erro padr&#227;o.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-110-04-0321-80044-gf03-pt.jpg"/></fig>
          </p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>A presente meta-an&#225;lise mostra que a RCH, em compara&#231;&#227;o com o CRM sem CEC, parece n&#227;o melhorar significativamente a mortalidade e morbidade a curto prazo das complica&#231;&#245;es p&#243;s-operat&#243;rias para pacientes com DAC. Estes resultados s&#227;o semelhantes &#224;s previs&#245;es da investiga&#231;&#227;o. Hu<xref ref-type="bibr" rid="B27">27</xref> comparou sistematicamente resultados cl&#237;nicos de curto prazo ap&#243;s RCH versus CRM sem CEC para o tratamento de DAC multivaso ou art&#233;ria coron&#225;ria esquerda principal, e a maioria dos resultados foi consistente com a an&#225;lise atual. No entanto, algumas diferen&#231;as entre as duas an&#225;lises tamb&#233;m devem ser mencionadas. N&#243;s exclu&#237;mos um estudo<xref ref-type="bibr" rid="B28">28</xref> devido ao pequeno tamanho da amostra (menos de 15 pacientes), procedimentos cir&#250;rgicos desatualizados (incis&#245;es de toracotomia de 8-10 cm), diferentes tipos de DES (cypher ou taxus), incerteza da LVEF basal (n&#227;o relatada) e alta heterogeneidade em an&#225;lise. N&#243;s tamb&#233;m colocamos tr&#234;s estudos recentes de alta qualidade nos dados agrupados para que todos os resultados sejam atualizados. E no presente estudo, nos concentramos em complica&#231;&#245;es p&#243;s-operat&#243;rias e tomamos o AVC como par&#226;metro final. Portanto, a an&#225;lise atual &#233; necess&#225;ria para uma melhor elucida&#231;&#227;o de RCH e CRM sem CEC.</p>
        <p>Para o nosso conhecimento, esta &#233; a primeira meta-an&#225;lise que compara os resultados cl&#237;nicos de m&#233;dio prazo entre RCH e CRM sem CEC at&#233; agora. Nossos dados mostram que a RCH possui uma taxa de ECCAM de m&#233;dio prazo menor, enquanto a CRM sem CEC mostra um melhor resultado na RVA de m&#233;dio prazo. E nenhuma diferen&#231;a significativa na mortalidade intermedi&#225;ria foi detectada entre os dois grupos. Os pacientes submetidos ao procedimento h&#237;brido t&#234;m resultados cl&#237;nicos de m&#233;dio prazo relativamente melhores provavelmente devido &#224; manipula&#231;&#227;o mioc&#225;rdica reduzida e &#224; ativa&#231;&#227;o da coagula&#231;&#227;o.<xref ref-type="bibr" rid="B26">26</xref> Foi amplamente reconhecido que a destrui&#231;&#227;o ou ruptura de placas ateroscler&#243;ticas durante a manipula&#231;&#227;o a&#243;rtica cir&#250;rgica resulta em uma causa importante de acidente vascular cerebral.<xref ref-type="bibr" rid="B29">29</xref> Uma vez que a aorta &#233; mais ou menos afetada no procedimento cir&#250;rgico, ainda n&#227;o est&#225; claro se a CRM sem CEC pode diminuir a taxa de AVC no p&#243;s-operat&#243;rio em compara&#231;&#227;o com a CRM com CEC. Em contraste, o enxerto na RCH envolve somente a art&#233;ria CDA enquanto outras art&#233;rias coron&#225;rias s&#227;o tratadas pela ICP. Como resultado, a baixa taxa de complica&#231;&#245;es neurol&#243;gicas torna-se uma das principais vantagens do RCH. Na an&#225;lise atual, no entanto, n&#227;o detectamos diferen&#231;a significativa na taxa de AVC entre a CRM sem CEC e a RCH em um seguimento de curto prazo, o que parece ser contradit&#243;rio com algumas an&#225;lises anteriores.</p>
        <p>Por outra parte, Song et al.,<xref ref-type="bibr" rid="B26">26</xref> relataram que mais pacientes no grupo CRM sem CEC sofrem de AVC do que no grupo RCH em um seguimento de 30 meses, o que indica que as diferen&#231;as podem ser bem reconhecidas em um seguimento de longo prazo. Nos &#250;ltimos anos, os avan&#231;os t&#233;cnicos na CRM sem CEC utilizam a t&#233;cnica <italic>no-touch</italic> para evitar manipula&#231;&#227;o a&#243;rtica durante o enxerto. Um estudo retrospectivo mostrou que a CRM sem CEC com t&#233;cnica <italic>no-touch</italic> poderia melhorar o progn&#243;stico, minimizando as complica&#231;&#245;es neurol&#243;gicas e a morbidade.<xref ref-type="bibr" rid="B30">30</xref> Emmert et al.,<xref ref-type="bibr" rid="B31">31</xref> tamb&#233;m relataram que a CRM sem CEC a&#243;rtica <italic>no touch</italic> apresentou resultados neurol&#243;gicos superiores aos da CRM com CEC e que a t&#233;cnica <italic>no touch</italic>, deve ser adequadamente aplicada. Halbersma et al.,<xref ref-type="bibr" rid="B32">32</xref> investigaram os resultados cl&#237;nicos de quatro anos ap&#243;s a CRM sem CEC com a t&#233;cnica <italic>no touch</italic> e concluiu que &#233; uma escolha e eficiente para pacientes com DAC multivaso ou art&#233;ria principal esquerda. Os dados reunidos indicam que a combina&#231;&#227;o do CRM sem CEC e a estrat&#233;gia <italic>clampless</italic> pode reduzir o risco de AVC. No entanto, a maior limita&#231;&#227;o da CRM sem CEC no-touch &#233; o seu grau t&#233;cnico mais elevado, raz&#227;o pela qual n&#227;o &#233; aplic&#225;vel por todas as equipes cir&#250;rgicas ou para todos os pacientes.<xref ref-type="bibr" rid="B33">33</xref> No entanto, devem ser feitas mais investiga&#231;&#245;es de pesquisa para comparar CRM sem CEC <italic>no touch</italic> e RCH <italic>no touch</italic>.</p>
        <p>Na an&#225;lise real, nem RCH estagiada nem RCH simult&#226;nea fazem diferen&#231;a nos resultados a curto prazo, o que &#233; consistente com os estudos anteriores.<xref ref-type="bibr" rid="B27">27</xref> Em geral, existem tr&#234;s estrat&#233;gias para RCH: (1) a realiza&#231;&#227;o de enxertos de AMIE-CDA primeiro, seguido pela ICP, o intervalo varia de v&#225;rias horas a algumas semanas; (2) vice-versa; (3) Enxerto AMIE-CDA e ICP combinados ao mesmo tempo em uma unidade de opera&#231;&#227;o h&#237;brida. A sequ&#234;ncia &#243;ptima de enxerto de AMIE-CDA e ICP foi debatida, mas continua pouco clara. Na verdade, a maioria dos centros escolhe seus pr&#243;prios procedimentos cir&#250;rgicos principalmente com base nas prefer&#234;ncias dos m&#233;dicos, considera&#231;&#245;es de pacientes, problemas econ&#244;micos e recursos dispon&#237;veis. Embora v&#225;rios estudos tenham indicado que tanto a HCR simult&#226;nea quanto a estagiada contribuem para resultados excelentes, a maioria dos centros prefere adotar a &#250;ltima com o enxerto de AMIE-CDA realizado primeiro.<xref ref-type="bibr" rid="B34">34</xref> A abordagem da CABG &#233; recomendada pelos American College of Cardiology Foundation/American Heart Association<xref ref-type="bibr" rid="B35">35</xref> e tem algumas vantagens &#243;bvias. Pode reduzir a sobreposi&#231;&#227;o de duas equipes diferentes para que elas possam agir da maneira que lhe for mais familiar e evitar interagir uma com a outra na sala de opera&#231;&#227;o. Ent&#227;o, as estrat&#233;gias anti-plaquet&#225;rias e antitromb&#243;ticas podem ser bem administradas e ajustadas de acordo com m&#233;dicos das diferentes equipes.<xref ref-type="bibr" rid="B36">36</xref> No entanto, as desvantagens incluem que os pacientes devem sofrer pelo menos duas cirurgias e precisam de mais tempo para se recuperar. Al&#233;m disso, a tend&#234;ncia a hemorragia e a sobrecarga renal tamb&#233;m merecem bastante aten&#231;&#227;o. Atualmente, nenhum estudo comparou os resultados cl&#237;nicos da RCH estagiada com a RCH simult&#226;nea diretamente, ent&#227;o &#233; preciso fazer mais pesquisas nesse sentido.</p>
        <p>Na presente an&#225;lise, tamb&#233;m confirmamos que a RCH aparentemente diminui o tempo de ventila&#231;&#227;o, a interna&#231;&#227;o da UTI, a interna&#231;&#227;o hospitalar e a taxa de transfus&#227;o de sangue em rela&#231;&#227;o &#224; CRM sem CEC. Embora esses elementos n&#227;o possam influenciar diretamente nos principais resultados, eles tamb&#233;m s&#227;o crit&#233;rios importantes para julgar um procedimento cir&#250;rgico. V&#225;rios motivos podem explicar essas vantagens da RCH. Com o desenvolvimento de procedimentos cir&#250;rgicos, a t&#233;cnica endosc&#243;pica e a mini incis&#227;o s&#227;o amplamente utilizadas na RCH para ajudar aos pacientes a aliviar o sofrimento e se recuperar antes.<xref ref-type="bibr" rid="B37">37</xref> E o estabilizador-retractor, como o rob&#244;, fornece um acesso para que o enxerto de AMIE_CDA possa ser realizado com precis&#227;o com toracotomia ou esternotomia minimamente invasiva.<xref ref-type="bibr" rid="B38">38</xref> Praticamente, com a ajuda de um rob&#244; cir&#250;rgico, temos um excelente campo visual e reduzimos o tempo de opera&#231;&#227;o. No entanto, alguns inconvenientes da RCH tamb&#233;m merecem nossa aten&#231;&#227;o. Nosso estudo detecta que o procedimento h&#237;brido exigiu um tempo de opera&#231;&#227;o mais longo e custos hospitalares elevados muito maiores do que a CRM sem CEC. No estudo de Bachinsky et al.,<xref ref-type="bibr" rid="B23">23</xref> apesar dos baixos custos p&#243;s-operat&#243;rios, o grupo RCH ainda precisa de mais custos hospitalares em geral, devido aos maiores custos processuais. Consequentemente, os pr&#243;s e contras da RCH devem ser pesados e considerados cuidadosamente antes da opera&#231;&#227;o.</p>
        <p>Algumas limita&#231;&#245;es da presente an&#225;lise tamb&#233;m devem ser enfatizadas. Primeiro, todos os estudos inclu&#237;dos pertencem a estudos observacionais e, at&#233; &#224; data, nenhum ECR &#250;nico foi realizado. Em segundo lugar, alguns estudos inclu&#237;dos cont&#234;m amostras relativamente pequenas (menos de 50 pacientes) e ainda h&#225; desequil&#237;brios no n&#250;mero de pacientes entre os grupos, de modo que o desvio dos resultados pode inevitavelmente existir. Em terceiro lugar, a pat&#234;ncia a longo prazo &#233; mais convincente do que a dos resultados a curto e m&#233;dio prazo, mas at&#233; agora foram publicadas muito poucas refer&#234;ncias de acompanhamento a longo prazo. Finalmente, alguns fatores n&#227;o controlados podem interferir com a an&#225;lise atual. Vari&#225;veis como a raz&#227;o de g&#234;nero e a FEVE no in&#237;cio do estudo n&#227;o foram ajustadas. E v&#225;rios procedimentos cir&#250;rgicos, stents (DES ou stent nu), bem como estrat&#233;gias antiplaquet&#225;rias, tamb&#233;m podem alterar a precis&#227;o dos resultados.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#245;es</title>
        <p>A RCH mostra resultados semelhantes com a CRM sem CEC em resultados cl&#237;nicos de curto prazo. A RCH diminui o tempo de ventila&#231;&#227;o, perman&#234;ncia na UTI, interna&#231;&#227;o hospitalar, taxa de transfus&#227;o sangu&#237;nea e aumentou o tempo de opera&#231;&#227;o e os custos de hospitaliza&#231;&#227;o. Embora a repeti&#231;&#227;o da revasculariza&#231;&#227;o vascular seja maior com a RCH, possui uma taxa menor de ECCAM no m&#233;dio prazo e pode fornecer uma alternativa segura e reprodut&#237;vel para pacientes com DAC multivaso.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
        <fn 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>
    </back>
  </sub-article>
</article>
