<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "https://jats.nlm.nih.gov/publishing/1.1/JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.6" 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">kkM8Fcn78DZ9Mrz8sKYKkqM</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2017001500599</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20170174</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2017005022105</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Percutaneous Intervention in ST-Elevation Myocardial Infarction: Culprit-only or Complete Revascularization?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Os&#243;rio</surname>
            <given-names>Ana Paula Susin</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Quadros</surname>
            <given-names>Alexandre Schaan de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Jos&#233; Luiz da Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Portal</surname>
            <given-names>Vera Lucia</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <institution content-type="orgname">Funda&#231;&#227;o Universit&#225;ria de Cardiologia</institution>
          <institution content-type="orgdiv1">Instituto de Cardiologia</institution>
          <addr-line>
            <named-content content-type="city">Porto Alegre</named-content>
            <named-content content-type="state">RS</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto de Cardiologia/Funda&#231;&#227;o Universit&#225;ria de Cardiologia (IC/FUC), Porto Alegre, RS - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Vera Lucia Portal &#8226;</bold> Rua Luciana de Abreu, 471, sala 603. Postal Code 90570-080, Moinhos de Vento, Porto Alegre, RS - Brazil. E-mail: <email>vera.portal@hotmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research and Acquisition of data: Os&#243;rio APS, Vieira JLC, Portal VL; Analysis and interpretation of the data, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Os&#243;rio APS, Quadros AS, Vieira JLC, Portal VL.</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>27</day>
        <month>11</month>
        <year>2017</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>12</month>
        <year>2017</year>
      </pub-date>
      <volume>109</volume>
      <issue>6</issue>
      <fpage>599</fpage>
      <lpage>605</lpage>
      <history>
        <date date-type="received">
          <day>25</day>
          <month>12</month>
          <year>2016</year>
        </date>
        <date date-type="rev-recd">
          <day>02</day>
          <month>05</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>05</day>
          <month>07</month>
          <year>2017</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <p>The best approach of multivessel coronary artery disease in the context of acute myocardial infarction with ST segment elevation and primary percutaneous coronary intervention is one of the main reasons for controversy in cardiology. Although the main global guidelines do not recommend routine complete revascularization in these patients, recent randomized clinical trials have demonstrated benefit of this approach in reducing cardiovascular outcomes. For this reason, an adequate review of this evidence is essential in order to establish scientifically based strategy and achieve better outcomes for these patients who present with acute myocardial infarction. This review aims to present objectively the most recent evidence available on this topic.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Myocardial Infarction</kwd>
        <kwd>Myocardial Revascularization</kwd>
        <kwd>Percutaneous Coronary Intervention</kwd>
        <kwd>Coronary Artery Disease</kwd>
        <kwd>Stents</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>The primary percutaneous coronary intervention (PPCI) currently represents the treatment of choice for acute ST-Elevation Myocardial Infarction (STEMI).<xref ref-type="bibr" rid="B1">1</xref> However, despite its undeniable benefit, some issues related to its appropriate use are still controversial.</p>
      <p>Approximately 40 to 50% of patients with STEMI have multivascular coronary artery disease (CAD),<xref ref-type="bibr" rid="B2">2</xref> although most of those individuals are asymptomatic until their acute manifestation.<xref ref-type="bibr" rid="B3">3</xref> It is known that, when compared to patients with CAD with involvement of a single vase, they have higher rates of mortality and of recurrent non-fatal infarction incidence.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref> Brazilian data, from the Cardiology Institute of Rio Grande do Sul, show that in a total of 2,469 patients treated due to STEMI during the period from 2010 to 2014, about 30 and 20% of them had two and three vessels affected, respectively. In a multivariate analysis, the three-vessel CAD was proven a strong predictor of mortality in 30 days (OR 3.39; 95%CI 1.47-3.87; p &lt; 0.001).<xref ref-type="bibr" rid="B6">6</xref>
			</p>
      <p>The long-term prognosis of acute myocardial infarction (AMI) associated with multivascular CAD is worse, probably due to a series of pathological mechanisms, such as: additional instability of other atherosclerotic plaques; impairment in myocardial perfusion caused by endothelial dysfunction; microvascular spasm or inflammation; and contractility reduction in non-infarcted areas. The worse log-term outcomes may also be related to the higher age of patients, in addition to more risk factors for atherosclerosis and decreased left ventricular function in individuals with multivascular CAD.<xref ref-type="bibr" rid="B7">7</xref> In this context, the benefits of multiarterial revascularization may be related to decreased risk of new coronary occlusions, decreased total ischemic load and improves potential for collateral circulation.</p>
      <p>Thus, there is an important questioning regarding the best PPCI strategy in these individuals: the treatment solely of the lesion responsible for the AMI or the complete revascularization, with angioplasty of stenosis in arteries not related to AMI.</p>
      <p>Metanalyses of observational studies, mostly records, have demonstrated conflicting results when PPCI is performed in arteries which are not responsible for the AMI.<xref ref-type="bibr" rid="B8">8</xref><sup>-</sup><xref ref-type="bibr" rid="B10">10</xref>
			</p>
      <p>Cavender et al.<xref ref-type="bibr" rid="B8">8</xref> collected data from the National Cardiovascular Data Registry, an American registry of 708,481 hospital admissions during the years of 2004 to 2007, with the objective of determining the prevalence, the predictors and the in-hospital outcomes of complete revascularization in AMI. Patients submitted to the multivascular approach were more severe, with greater incidence of cardiogenic shock, heart failure (HF), left ventricular ejection fraction lower than 30% and impairment of the proximal anterior descending artery. In-hospital mortality was higher among those submitted to complete revascularization (7.9% <italic>versus</italic> 5.1%; p &lt; 0.01). Patients in cardiogenic shock who received PCI of arteries not responsible for the AMI also had higher mortality (36.5% <italic>versus</italic> 27.8%; OR 1.54; 95%CI 1.22-1.95).</p>
      <p>Bangalore et al.<xref ref-type="bibr" rid="B9">9</xref> collected data from 19 studies (61,764 patients) evaluating multivascular AMI and CAD, with the objective to compare early (&lt; 30 days) and late outcomes submitted to PCI solely of the responsible artery or complete revascularization. Of the 19 studies, only 2 were randomized. Patients who underwent the staged strategy were excluded. There was no significant difference in early mortality outcomes, AMI, cerebrovascular accident (CVA) and revascularization of the target vessel. In the long-term (2 &#177; 1.1 years), there was no difference in mortality, AMI, CVA, revascularization of the target vessel and stent thromboses, though there were reductions of 33% in mortality, 43% in the need of percutaneous intervention and 53% in the myocardial revascularization surgery. There was a significant reduction of adverse cardiovascular events when the complete revascularization strategy was used, when compared to the approach solely of the responsible artery (OR 0.60; 95%CI 0.50-0.72).</p>
      <p>In metanalysis of 11 studies, Sethi et al.<xref ref-type="bibr" rid="B10">10</xref> compared the outcomes of 4,640 patients submitted to complete revascularization during PPCI procedure or in the same hospitalization with 27,394 patients treated only with PPCI of the responsible artery by AMI. Only 2 of them were randomized clinical trials (RCTs), 8 were observational studies and 1 was a control case. Most patients were hemodynamically stable. There was no difference in relation to greater cardiovascular events (OR 0.95; 95%CI 0.47-1.90) and to long-term mortality (OR 1.10; 95%CI 0.76-1.59). There was heterogeneity among the studies, in addition to the absence of specific designs to answer this question.</p>
      <p>Two great metanalyses of observational studies,<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> with over 40,000 patients each, reported the complete approach during the PPCI procedure was associated with higher mortality, while the staged intervention (performed later during hospitalization or 30 after the acute event) was associated to reduced mortality. Small RCTs did not show improvement in either outcomes nor prognostic of patients treated with complete revascularization in acute context.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref>
			</p>
      <p>In pair and network metanalysis, involving 4 prospective studies and 14 retrospective studies with a total of 40,280 patients, Vlaar et al.<xref ref-type="bibr" rid="B11">11</xref> evaluated three revascularization strategies: 1) PCI solely of the artery responsible for the AMI; 2) immediate complete revascularization of one or more arteries not responsible for the AMI; 3) staged revascularization during hospitalization of one or more arteries not related to the AMI. In paired analysis, it could be observed that the staged revascularization associated to lower short- and long-term mortality, when compared to PCI of the responsible artery or immediate complete revascularization. Immediate complete revascularization had higher mortality rates in the short and long terms. Network metanalysis showed staged revascularization would consistently associate with lower mortality.</p>
      <p>Similarly, Bainey et al.<xref ref-type="bibr" rid="B12">12</xref> performed systematic reviews and metanalysis of 26 studies (46,324 patients) comparing revascularization strategies for multivascular CAD in AMI. Only 3 studies were randomized. There was no difference for in-hospital mortality when compared to PCI solely of the responsible artery with complete revascularization, however, this mortality was increased when the approach of other arteries was performed during the same procedure as the PPCI. Reduced in-hospital mortality was observed with complete staged revascularization. With the strategy of complete revascularization, there was a reduction in the long-term mortality and in the need for new interventions.</p>
      <sec>
        <title>Guidelines recommendations</title>
        <p>The main guidelines on the treatment of STEMI have discouraged PCI of arteries not responsible for AMI. According to ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST-Segment Elevation,<xref ref-type="bibr" rid="B15">15</xref> published in 2012 by the European Society of Cardiology, there is no evidence for emergency intervention in lesions which are not responsible for AMI. The approach of multivascular CAD during PPCI is only justified in cases of cardiogenic shock with presence of multiple critical stenosis or of highly unstable lesions (angiographic signs of thrombi or rupture of the lesion) or of evidence of persistent ischemia in spite the angioplasty of the affected artery.</p>
        <p>On the other hand, the American directive, published in 2013 (2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction),<xref ref-type="bibr" rid="B16">16</xref> considered as class III (causing damage) the angioplasty of arteries not responsible for AMI, in the context of PPCI in patients without hemodynamic compromise. However, with the newly observed evidences, especially after the publication of the PRAMI study,<xref ref-type="bibr" rid="B17">17</xref> in 2013, an update of this guideline was published, considering class IIb the angioplasty of the artery which was not responsible for the PPCI or as staged procedure prior to hospital discharge.<xref ref-type="bibr" rid="B18">18</xref>
				</p>
        <p>More recently, the Brazilian guideline directive (<italic>V Diretriz da Sociedade Brasileira de Cardiologia sobre Tratamento do Infarto Agudo do Mioc&#225;rdio com Supradesn&#237;vel do Segmento ST</italic>), published in 2015, recommends the percutaneous approach should be dedicated to the artery responsible for the AMI. The immediate revascularization of other arteries not responsible for the event during PPCI may be considered in patients selected, as in cases of less complicated severe stenosis located in the same coronary system related to the infected vessel and according to the criterious evaluation of the clinical and hemodynamic situation of the patient (IIb,B).<xref ref-type="bibr" rid="B19">19</xref>
				</p>
      </sec>
      <sec>
        <title>Main studies</title>
        <p>One of the first RCTs to approach the theme was conducted in an Italian center by Politi et al.. Two hundred and fourteen consecutive patients were excluded with multivascular AMI and CAD in the context of PPCI. Multivascular disease was defined as the presence of stenosis greater than 70% in two or more epicardial coronaries or their main branches, in visual angiographic evaluation. Before their first angioplasty, patients were randomized into three main strategies: PCI solely of the responsible artery, complete staged revascularization or complete revascularization at the moment of PPCI.<xref ref-type="bibr" rid="B20">20</xref>
				</p>
        <p>The primary outcome considered consisted of greater cardiac events, defined by: cardiac and non-cardiac death, in-hospital mortality, reinfarction, rehospitalization due to acute coronary syndrome and need for a new revascularization. After follow-up of 2.5 years, at least one greater cardiac event was identified in 42 (50%) of the patients treated only with PCI of the responsible artery, in 13 (20%) of the group of complete staged revascularization and in 15 (23.1%) of the ones submitted to complete revascularization during PPCI, displaying significant difference (p &lt; 0.001). In-hospital mortality, need for new revascularizations and rehospitalization occurred more frequently among patients treated with PCI solely of the responsible artery. There was no difference in relation to mortality among the three groups.</p>
        <p>The PRAMI Study - Randomized Trial of Preventive Angioplasty in Myocardial Infarction,<xref ref-type="bibr" rid="B17">17</xref> published in 2013, was the first RCT of greater magnitude to compare angioplasty of the artery responsible for the AMI to the complete revascularization of lesions in other arteries with no responsibility during the index procedure. This open-labeled study randomized 465 patients submitted to PPCI. Patients selected for complete revascularization, all angiographically stenosis greater than 50% were treated in the same procedure of the PPCI. The primary outcome considered consisted of deaths by all causes, non-fatal AMI or refractory angina. After an average follow-up of 23 months, the study was interrupted early due to a significantly high difference between the groups. There was reduction of 65% in the primary outcome in the group submitted to complete revascularization during PPCI (HR 0.35; 95%CI 0.21-0.58; p &lt; 0.001). A similar reduction was also found when analyzing the primary outcome consisted of cardiac death or non-fatal AMI (HR 0.36; 95%CI 0.18-0.73). The group submitted to complete revascularization presented higher time of procedure and contrast volume, however complication rates, including CVA, bleeding and contrast-induced nephropathy were similar between the groups.</p>
        <p>This was a study on preventive angioplasty, treating other lesions above 50%, in addition to the responsible coronary without worrying whether they were causing limitations to the flow. Critical reviews on this study point out its unblinded design as a flaw, once that patients were aware they had untreated lesions, thus making the findings susceptible to bias. Besides, patient in the control group were not tested for the presence of ischemia due to residual lesions, being investigated and treated only if refractory angina was observed. When compared to other studies on the same matter, it should be emphasized that the complete staged revascularization was not evaluated in a moment other than in PPCI.</p>
        <p>Posteriorly, the CvLPRIT study - Complete versus Lesion-only Primary PCI Trial,<xref ref-type="bibr" rid="B21">21</xref> RCT, open, multicentered, conducted in seven centers in the United Kingdom, was published in 2015. Two hundred and ninety-six patients with STEMI were randomized for PCI of the compromised artery or complete revascularization in index admission. Allocation into the groups was performed after angiography with stenosis greater than 50% in arteries not responsible for the AMI. The complete revascularization should be performed in the same procedure, though the operator could choose to take on the procedure at some other moment before hospital discharge, including, thus, the staged revascularization strategy.</p>
        <p>After an average follow-up of 12 months, there was a significant reduction (55%) in the primary outcome consisted of mortality, recurrent AMI, HF or revascularization guided by ischemia (10% <italic>versus</italic> 21%; HR 0.45; p = 0.009) in patients submitted to complete revascularization. The reduction of the primary outcome was evident early within the first 30 days, although not significantly (p = 0.055).</p>
        <p>Of the 150 patients selected for complete revascularization, 64% of them were treated during the same procedure as PPCI, subgroup in which a tendency to greater benefit was observed. It should be noted, however, that the study did not have a specific design for this kind of analysis.</p>
        <p>As expected, patients submitted to complete revascularization had a greater number of stents implanted, as well as higher time of procedure and contrast volume used. The safety outcomes considered, including CVA, larger bleeding and contrast-induced nephropathy, were similar between the groups.</p>
        <p>It should be noted that, although positive results have been found, the CvLPRIT Trial did not have sufficient statistical power to detect difference in important components of the primary outcome, such as death and AMI.</p>
        <p>Furthermore, in attempting to get an answer on the best management of multivascular CAD in PPCI, Engstrom et al. carried out the DANAMI3-PRIMULTI study,<xref ref-type="bibr" rid="B22">22</xref> published in 2015. This open RCT compared a complete revascularization strategy guided by a fractional flow reserve (FFR) two days after the index procedure with no additional intervention after PPCI. Six hundred and twenty-seven patients were randomized in two centers in Danmark, being considered as primary outcome a set of mortality by all causes, reinfarction or revascularization guided by ischemia (either subjective or objective) of arteries not related to the AMI.</p>
        <p>After follow-up of 27 months, there was a significant decrease of 44% in the primary outcome analyzed (HR 0.56; 95%CI 0.38-0.83; p = 0.004) in the group submitted to PCI of the arteries not responsible for the AMI. However, when analyzed individually, mortality rates due to all causes and reinfarction were similar in both groups, while the complete revascularization group had better results because of the need for less reinterventions due to refractory angina.</p>
        <p>The real benefits of complete revascularization are questioned here, once there were no differences in isolated harsh outcomes, such as mortality and reinfarction, and the fact that primary outcome reduction was due, primarily, to the need for new revascularizations.</p>
        <p>In a metanalysis consisted of three RCTs carried out until September 2013, with a total of 748 patients (416 randomized for complete revascularization and 322 for PCI of the responsible artery), Pandit et al. showed the benefits of preventive PCI. In the group treated with complete revascularization during PPCI, there was a significant reduction in cardiovascular death (HR 0.39; 95%CI 0.18-0.83; p = 0.01), in the need for new revascularizations (OR 0.28; 95%CI 0.18-0.44; p = 0.00001) and in non-fatal AMI (OR 0.38; 95%CI 0.20-0.75; p = 0.005).<xref ref-type="bibr" rid="B23">23</xref>
				</p>
        <p>Spencer et al. Carried out another metanalysis, in which all RCTs were included, until 2015, comparing complete revascularization <italic>versus</italic> PCI solely of the artery responsible for the AMI. Five clinical trials were included, with a total of 1,568 patients. Complete revascularization was associated to the reduced need for new revascularization (RR 0.36; 95%CI 0.27-0.49) and decreased recurrent AMI (RR 0.41; 95%CI 0.30-0.57). However, when considering the total mortality, there was no significant difference between the groups (RR 0.82; 95%CI 0.53-1.26).<xref ref-type="bibr" rid="B24">24</xref>
				</p>
        <p>Tarantini et al. performed a systematic paired review and a network metanalysis with the objective of verifying which is the best therapeutic strategy in patients with ST-Elevation AMI and multivascular CAD. We included prospective and retrospective studies published between 2001 and 2015. Analyses were carried out for three intervention strategies: 1) PCI solely of the affected artery; 2) complete revascularization during PPCI procedure; and 3) complete staged revascularization during hospitalization.<xref ref-type="bibr" rid="B25">25</xref> Thirty-two studies were included (13 prospective and 19 retrospective ones), with a total of 54,148 patients. The paired analysis showed the complete staged revascularization was associated to lower mortality in the short and long terms, when compared to PCI solely of the artery responsible and complete revascularization during PPCI. On the other hand, the revascularization solely of the responsible artery in relation to a complete revascularization during PPCI presented reduced mortality. In the network analysis, the complete staged revascularization associated consistently to improved survival rates. <xref ref-type="table" rid="t1">Table 1</xref> describes the main findings of the RCTs presented.</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Main characteristics of randomized clinical trials compared to percutaneous coronary intervention solely of the responsible artery versus complete revascularization of acute myocardial infarction with ST Elevation</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">Study</th>
                <th align="center">Type of study</th>
                <th align="center">N</th>
                <th align="center">PCI non-responsible arteries</th>
                <th align="center">Primary outcome (composed)</th>
                <th align="center">Result (primary outcome)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Politi et al.</td>
                <td align="center">RCT</td>
                <td align="center">214</td>
                <td align="center">Angiography &gt; 70%</td>
                <td align="center">Cardiac and non-cardiac death, in-hospital death, reinfarction, rehospitalization due to ACS, new revascularization</td>
                <td align="center">Reduction of greater events with complete revascularization (p &lt; 0.001)</td>
              </tr>
              <tr>
                <td align="left">PRAMI</td>
                <td align="center">RCT</td>
                <td align="center">465</td>
                <td align="center">Angiography &gt; 50%</td>
                <td align="center">Death by all causes, Non-fatal AMI, refractory angina</td>
                <td align="center">Reduction of 65% with complete revascularization (HR 0.35; 95%CI 0.21-0.58; p &lt; 0.001)</td>
              </tr>
              <tr>
                <td align="left">CvLPRIT</td>
                <td align="center">RCT</td>
                <td align="center">296</td>
                <td align="center">Angiography &gt; 50%</td>
                <td align="center">Mortality, recurrent AMI, CI, revascularization guided by ischemia</td>
                <td align="center">Reduction of 55% with complete revascularization (10% <italic>vs</italic> 21%; HR 0.45; p = 0.009)</td>
              </tr>
              <tr>
                <td align="left">DANAMI-3-PRIMULTI</td>
                <td align="center">RCT</td>
                <td align="center">627</td>
                <td align="center">FFR &lt; 0.80</td>
                <td align="center">Mortality by all causes, reinfarction, revascularization guided by ischemia</td>
                <td align="center">Reduction of 44% with complete revascularization (HR 0.56; 95%CI 0.38-0.83; p = 0.004).</td>
              </tr>
              <tr>
                <td align="left">COMPARE-ACUTE</td>
                <td align="center">RCT</td>
                <td align="center">885</td>
                <td align="center">FFR &#8804; 0.80</td>
                <td align="center">Mortality by all causes, non-fatal AMI, need fo any revascularization, cerebrovascular events</td>
                <td align="center">Reduction of 65% with complete revascularization (HR 0.35; 95%CI 0.22-0.55; p &lt; 0.001)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>RCT: randomized clinical trials; HR: hazard ratio; CI: confidence interval; ACS: acute coronary syndrome.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Recently, Smits et al. published the results of the Compare-Acute multicenter clinical trial, which randomized 885 patients with AMI and multivascular CAD submitted to PPCI. These patients were compared, in a ratio of 1:2, for the complete revascularization guided by FFR or PCI solely of the artery responsible for the AMI. We included patients with indication for PPCI and who had had other stenosis of, at least, 50% in quantitative or visual angiographic evaluation. All patients were submitted to FFR, however the ones selected for treatment of the affected artery and their assistant doctors were not informed on the results. In the randomized group, PCI of the arteries not responsible for the AMI would be conducted if &#8804; 0.80, preferably during the same PPCI procedure. The operating doctor would be able to choose to perform a complete revascularization at another moment, provided it would be carried out during the hospitalization and within 72 hours.<xref ref-type="bibr" rid="B26">26</xref>
				</p>
        <p>The primary outcome considered was the one consisted of death by all causes, non-fatal AMI, need for any revascularization and cerebrovascular events within 12 months. After one year, the primary outcome occurred in 23 patients of the complete revascularization group and in 121 of those treated only with PCI for the affected artery (HR 0.35; 95%CI 0.22-0.55; p &lt; 0.001). There was no significant difference between the groups, when analyzed the isolated outcomes of death by all the causes and AMI. There was a significant decrease in the need for new revascularization in the complete revascularization group (HR 0.32; 95%CI 0.20- 0.54; p &lt; 0.001). No differences were observed in relation to the safety outcomes analyzed.</p>
        <p>Although with higher number of selected patients and also with the use of FFR functional evaluation, the study once again shows positive results at the cost of reducing the need for new revascularizations. Harsh outcomes, such as death and AMI, when analyzed in isolation, did not differ between groups.</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>Considering the results of the studies presented, the complete revascularization of arteries not responsible for the AMI seem to offer better results than just the clinical treatment. However, it should be noted they are studies with a small number of patients and with heterogeneous designs, having been used different criteria for the revascularization of non-responsible stenosis, whether angiographic or based on functional evaluation, such as the FFR. The small number of events observed in the studies available makes it rather difficult to be defined as for the benefits of this strategy in the mortality rates and recurrent infarction.</p>
      <p>Initially published metanalyses and registries failed to demonstrate the clear benefit of complete revascularization on PCI solely of the responsible artery. In the study by Cavender et al.,<xref ref-type="bibr" rid="B8">8</xref> this fact is possibly related to the greater severity of the patients treated with complete revascularization, most of them with reduced left ventricular ejection or in cardiogenic shock. Another limitation of these initial analyses is the great heterogeneity of the studies included, in addition to the absence of specific designs for the evaluation of greater cardiovascular outcomes, as in the study by Sethi et al.<xref ref-type="bibr" rid="B10">10</xref> On the other hand, more recent metanalyses with greater number of studies, although still mostly observational, start to point in favor of the benefit of complete revascularization, especially when carried out in a staged way. This benefit is confirmed with the publication of the main RCTs which, despite their limitations, hade an appropriate design to evaluate the best strategy.</p>
      <p>Another point to be considered is the appropriate moment to perform the complete revascularization - during the index procedure or in a staged way, during hospitalization. In the CvLPRIT study, patients treated in the index procedure had better results, despite the study not having been design for this evaluation. In DANAMI-3-PRIMULTI, patients were submitted to revascularization two days after the acute event, with reduced outcomes, although due to the need for new revascularizations. Logistic aspects of performing these multi-arterial procedures in patients with STEMI should be especially considered in our field, once they presuppose trained personnel, available material and clinical and surgical backup, which may not be available during procedures performed during late hours, for example.</p>
      <p>At present, some RCTs are underway in an attempt to elucidate the best therapeutic strategy in this context. Among them, the COMPLETE study (Complete versus Culprit-only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI trial),<xref ref-type="bibr" rid="B27">27</xref> designed to detect differences in cardiovascular death or AMI with complete staged revascularization <italic>versus</italic> PCI solely of the responsible artery. There is also the FRAME-STEMI trial, which will evaluate the revascularization strategies guided by FFR of the lesion compared to the traditional angiographic evaluation.<xref ref-type="bibr" rid="B28">28</xref>
			</p>
      <p>Despite the findings of the last clinical trials, there is still no definitive answer regarding the best treatment for multivascular CAD in STEMI and PPCI contexts.<xref ref-type="bibr" rid="B29">29</xref> Many particularities should be considered in the decision on which is the best moment for the approach of non-responsible arteries, among which, clinical characteristics of the patient, as well as angiographic characteristics of the lesion and of non-related arteries. For instance, it could be more prudent to postpone the complete revascularization when the angioplasty of the lesion was complex, requiring great volumes of contrast or resulting in unsatisfactory final flow. All the same, complex lesions, such as bifurcations, chronic, highly calcified occlusions may be treated at a later time.<xref ref-type="bibr" rid="B30">30</xref>
			</p>
      <p>The advantages and disadvantages of each intervention strategy should also be considered. The complete revascularization could be beneficial, once it allows for the fast reestablishment of blood flow, increasing the viable myocardial area and leading to an improvement of the left ventricular ejection fraction. In addition, it is related to reducing vascular complications through the lesser need for punctures and the reduced hospitalization time, promoting an increase in cost-effectiveness.</p>
      <p>On the other hand, the disadvantages of a complete revascularization include prolonged procedure time, with greater exposure to radiation and greater use of contrast, potentiating the risk of nephropathy by contrast. There is also higher risk of acute or subacute stent thrombosis due to the prothrombotic and pro-inflammatory AMI scenario.<xref ref-type="bibr" rid="B7">7</xref>
			</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>The multiarterial approach in a same procedure may be used in carefully selected patients, provided the situation described in the text presented are respected. An approach of the multiarterial treatment of all severe lesions in a step-by-step manner during the index hospitalization seems to be based on RCTs and in a great metanalysis recently published, and would be the alternative to be recommended in most cases considering the current evidence. However, until there is no definitive recommendation, the appropriate clinical judgement, of the interventionist along with the clinical cardiologist, remains as the standard strategy to be followed.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1 Bhatt DL. Timely PCI for STEMI--still the treatment of choice. N Engl J Med. 2013;368(15):1446-7. doi: 10.1056/NEJMe1302670.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bhatt</surname>
              <given-names>DL</given-names>
            </name>
          </person-group>
          <article-title>Timely PCI for STEMI--still the treatment of choice</article-title>
          <source>N Engl J Med</source>
          <year>2013</year>
          <volume>368</volume>
          <issue>15</issue>
          <fpage>1446</fpage>
          <lpage>1447</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJMe1302670</pub-id>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2 Park DW, Clare RM, Schulte PJ, Pieper KS, Shaw LK, Califf RM, et al. Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction. JAMA. 2014;312(19):2019-27. doi: 10.1001/jama.2014.15095.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Park</surname>
              <given-names>DW</given-names>
            </name>
            <name>
              <surname>Clare</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Schulte</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>Pieper</surname>
              <given-names>KS</given-names>
            </name>
            <name>
              <surname>Shaw</surname>
              <given-names>LK</given-names>
            </name>
            <name>
              <surname>Califf</surname>
              <given-names>RM</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction</article-title>
          <source>JAMA</source>
          <year>2014</year>
          <volume>312</volume>
          <issue>19</issue>
          <fpage>2019</fpage>
          <lpage>2027</lpage>
          <pub-id pub-id-type="doi">10.1001/jama.2014.15095</pub-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3 Toma M, Buller CE, Westerhout CM, Fu Y, O'Neill WW, Holmes DR, et al; APEX-AMI Investigators. Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial. Eur Heart J. 2010;31(14):1701-7. doi: doi: 10.1093/eurheartj/ehq129.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Toma</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Buller</surname>
              <given-names>CE</given-names>
            </name>
            <name>
              <surname>Westerhout</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Fu</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>O'Neill</surname>
              <given-names>WW</given-names>
            </name>
            <name>
              <surname>Holmes</surname>
              <given-names>DR</given-names>
            </name>
            <etal/>
          </person-group>
          <person-group person-group-type="author">
            <collab>APEX-AMI Investigators</collab>
          </person-group>
          <article-title>Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction insights from the APEX-AMI trial</article-title>
          <source>Eur Heart J</source>
          <year>2010</year>
          <volume>31</volume>
          <issue>14</issue>
          <fpage>1701</fpage>
          <lpage>1707</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehq129</pub-id>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4 Halkin A, Singh M, Nikolsky E, Grines CL, Tcheng JE, Garcia E, et al. Prediction of mortality after primary percutaneous coronary intervention for acute myocardial infarction: The CADILLAC risk score. J Am Coll Cardiol. 2005;45(9):1397-405. doi: 10.1016/j.jacc.2005.01.041.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Halkin</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Singh</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Nikolsky</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Grines</surname>
              <given-names>CL</given-names>
            </name>
            <name>
              <surname>Tcheng</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Garcia</surname>
              <given-names>E</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Prediction of mortality after primary percutaneous coronary intervention for acute myocardial infarction The CADILLAC risk score</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2005</year>
          <volume>45</volume>
          <issue>9</issue>
          <fpage>1397</fpage>
          <lpage>1405</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2005.01.041</pub-id>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5 Sorajja P, Gersh BJ, Cox DA, McLaughlin MG, Zimetbaum P, Costantini C, et al. Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Eur Heart J. 2007;28(14):1709-16. doi: 10.1093/eurheartj/ehm184.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sorajja</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Gersh</surname>
              <given-names>BJ</given-names>
            </name>
            <name>
              <surname>Cox</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>McLaughlin</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Zimetbaum</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Costantini</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction</article-title>
          <source>Eur Heart J</source>
          <year>2007</year>
          <volume>28</volume>
          <issue>14</issue>
          <fpage>1709</fpage>
          <lpage>1716</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehm184</pub-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6 Quadros AL. Temporal trends in characteristics, treatment and outcomes in ST-elevation myocardial infarction patients in the daily practice. In: Congresso da Sociedade de Cardiologia do Estado do Rio Grande do Sul, Gramado (RS); 6-7 de agosto, 2015. Arq Brasil Cardiol. 2015;105(4 supl.1):1-74.</mixed-citation>
        <element-citation publication-type="confproc">
          <person-group person-group-type="author">
            <name>
              <surname>Quadros</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <article-title>Temporal trends in characteristics, treatment and outcomes in ST-elevation myocardial infarction patients in the daily practice</article-title>
          <conf-name>Congresso da Sociedade de Cardiologia do Estado do Rio Grande do Sul</conf-name>
          <conf-loc>Gramado, RS</conf-loc>
          <conf-date>6-7 de agosto, 2015</conf-date>
          <source>Arq Brasil Cardiol</source>
          <year>2015</year>
          <volume>105</volume>
          <issue>4</issue>
          <supplement>supl.1</supplement>
          <fpage>1</fpage>
          <lpage>74</lpage>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7 Bates ER, Tamis-Holland JE, Bittl JA, O'Gara PT, Levine GN. PCI strategies in patients with ST-segment elevation myocardial infarction and multivessel coronary disease. J Am Coll Cardiol. 2016;68(10):1066-81. doi: 10.1016/j.jacc.2016.05.086.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bates</surname>
              <given-names>ER</given-names>
            </name>
            <name>
              <surname>Tamis-Holland</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Bittl</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>O'Gara</surname>
              <given-names>PT</given-names>
            </name>
            <name>
              <surname>Levine</surname>
              <given-names>GN</given-names>
            </name>
          </person-group>
          <article-title>PCI strategies in patients with ST-segment elevation myocardial infarction and multivessel coronary disease</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2016</year>
          <volume>68</volume>
          <issue>10</issue>
          <fpage>1066</fpage>
          <lpage>1081</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2016.05.086</pub-id>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8 Cavender MA, Milford-Beland S, Roe MT, Peterson ED, Weintraub WS, Rao SV. Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry). Am J Cardiol. 2009;104(4):507-13. doi: 10.1016/j.amjcard.2009.04.016.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Cavender</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Milford-Beland</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Roe</surname>
              <given-names>MT</given-names>
            </name>
            <name>
              <surname>Peterson</surname>
              <given-names>ED</given-names>
            </name>
            <name>
              <surname>Weintraub</surname>
              <given-names>WS</given-names>
            </name>
            <name>
              <surname>Rao</surname>
              <given-names>SV</given-names>
            </name>
          </person-group>
          <article-title>Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry)</article-title>
          <source>Am J Cardiol</source>
          <year>2009</year>
          <volume>104</volume>
          <issue>4</issue>
          <fpage>507</fpage>
          <lpage>513</lpage>
          <pub-id pub-id-type="doi">10.1016/j.amjcard.2009.04.016</pub-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9 Bangalore S, Kumar S, Poddar KL, Ramasamy S, Rha SW, Faxon DP. Meta-analysis of multivessel coronary artery revascularization versus culprit-only revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease. Am J Cardiol. 2011;107(9):1300-10. doi: 10.1016/j.amjcard.2010.12.039.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bangalore</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Kumar</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Poddar</surname>
              <given-names>KL</given-names>
            </name>
            <name>
              <surname>Ramasamy</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Rha</surname>
              <given-names>SW</given-names>
            </name>
            <name>
              <surname>Faxon</surname>
              <given-names>DP</given-names>
            </name>
          </person-group>
          <article-title>Meta-analysis of multivessel coronary artery revascularization versus culprit-only revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease</article-title>
          <source>Am J Cardiol</source>
          <year>2011</year>
          <volume>107</volume>
          <issue>9</issue>
          <fpage>1300</fpage>
          <lpage>1310</lpage>
          <pub-id pub-id-type="doi">10.1016/j.amjcard.2010.12.039</pub-id>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10 Sethi A, Bahekar A, Bhuriya R, Singh S, Ahmed A, Khosla S. Complete versus culprit only revascularization in acute ST elevation myocardial infarction: a meta-analysis. Catheter Cardiovasc Interv. 2011;77(2):163-70. doi: 10.1002/ccd.22647.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sethi</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bahekar</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Bhuriya</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Singh</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Ahmed</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Khosla</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
          <article-title>Complete versus culprit only revascularization in acute ST elevation myocardial infarction a meta-analysis</article-title>
          <source>Catheter Cardiovasc Interv</source>
          <year>2011</year>
          <volume>77</volume>
          <issue>2</issue>
          <fpage>163</fpage>
          <lpage>170</lpage>
          <pub-id pub-id-type="doi">10.1002/ccd.22647</pub-id>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11 Vlaar PJ, Mahmoud KD, Holmes DR, Van Valkenhoef G, Hillege HL, Van Der Horst IC, et al. Culprit vessel only versus multivessel and staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction: a pairwise and network meta-analysis. J Am Coll Cardiol. 2011;58(7):692-703. doi: 10.1016/j.jacc.2011.03.046.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vlaar</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>Mahmoud</surname>
              <given-names>KD</given-names>
            </name>
            <name>
              <surname>Holmes</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Van Valkenhoef</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Hillege</surname>
              <given-names>HL</given-names>
            </name>
            <name>
              <surname>Van Der Horst</surname>
              <given-names>IC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Culprit vessel only versus multivessel and staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction a pairwise and network meta-analysis</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2011</year>
          <volume>58</volume>
          <issue>7</issue>
          <fpage>692</fpage>
          <lpage>703</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2011.03.046</pub-id>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12 Bainey KR, Mehta SR, Lai T, Welsh RC. Complete vs culprit-only revascularization for patients with multivessel disease undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review and meta-analysis. Am Heart J. 2014;167(1):1-14.e2. doi: 10.1016/j.ahj.2013.09.018.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bainey</surname>
              <given-names>KR</given-names>
            </name>
            <name>
              <surname>Mehta</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Lai</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Welsh</surname>
              <given-names>RC</given-names>
            </name>
          </person-group>
          <article-title>Complete vs culprit-only revascularization for patients with multivessel disease undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction a systematic review and meta-analysis</article-title>
          <source>Am Heart J</source>
          <year>2014</year>
          <volume>167</volume>
          <issue>1</issue>
          <fpage>1</fpage>
          <lpage>14</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ahj.2013.09.018</pub-id>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13 Di Mario C, Mara S, Flavio A, Imad S, Antonio M, Anna P, et al. Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study. Int J Cardiovasc Intervent. 2004;6(3-4):128-33. doi: 10.1080/14628840310030441.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Di Mario</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Mara</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Flavio</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Imad</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Antonio</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Anna</surname>
              <given-names>P</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study</article-title>
          <source>Int J Cardiovasc Intervent</source>
          <year>2004</year>
          <volume>6</volume>
          <issue>3-4</issue>
          <fpage>128</fpage>
          <lpage>133</lpage>
          <pub-id pub-id-type="doi">10.1080/14628840310030441</pub-id>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14 Dambrink JH, Debrauwere JP, van 't Hof AW, Ottervanger JP, Gosselink AT, Hoorntje JC, et al. Non-culprit lesions detected during primary PCI: treat invasively or follow the guidelines?. EuroIntervention. 2010;5(8):968-75. PMID: 20542783. doi: 10.4244/EIJV5I8A162.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dambrink</surname>
              <given-names>JH</given-names>
            </name>
            <name>
              <surname>Debrauwere</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>van 't Hof</surname>
              <given-names>AW</given-names>
            </name>
            <name>
              <surname>Ottervanger</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Gosselink</surname>
              <given-names>AT</given-names>
            </name>
            <name>
              <surname>Hoorntje</surname>
              <given-names>JC</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Non-culprit lesions detected during primary PCI: treat invasively or follow the guidelines?</article-title>
          <source>EuroIntervention</source>
          <year>2010</year>
          <volume>5</volume>
          <issue>8</issue>
          <fpage>968</fpage>
          <lpage>975</lpage>
          <pub-id pub-id-type="pmid">20542783</pub-id>
          <pub-id pub-id-type="doi">10.4244/</pub-id>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15 Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, Borger MA, et al; Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33(20):2569-619. doi: 10.1093/eurheartj/ehs215.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Steg</surname>
              <given-names>PG</given-names>
            </name>
            <name>
              <surname>James</surname>
              <given-names>SK</given-names>
            </name>
            <name>
              <surname>Atar</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Badano</surname>
              <given-names>LP</given-names>
            </name>
            <name>
              <surname>Lundqvist</surname>
              <given-names>CB</given-names>
            </name>
            <name>
              <surname>Borger</surname>
              <given-names>MA</given-names>
            </name>
            <etal/>
          </person-group>
          <person-group person-group-type="author">
            <collab>Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology</collab>
          </person-group>
          <article-title>ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation</article-title>
          <source>Eur Heart J</source>
          <year>2012</year>
          <volume>33</volume>
          <issue>20</issue>
          <fpage>2569</fpage>
          <lpage>2619</lpage>
          <pub-id pub-id-type="doi">10.1093/eurheartj/ehs215</pub-id>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16 Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, et al; American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61(4):e78-140. doi: 10.1016/j.jacc.2012.11.019.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gara</surname>
              <given-names>PT</given-names>
            </name>
            <name>
              <surname>Kushner</surname>
              <given-names>FG</given-names>
            </name>
            <name>
              <surname>Ascheim</surname>
              <given-names>DD</given-names>
            </name>
            <name>
              <surname>Casey</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Chung</surname>
              <given-names>MK</given-names>
            </name>
            <name>
              <surname>de Lemos</surname>
              <given-names>JA</given-names>
            </name>
            <etal/>
          </person-group>
          <person-group person-group-type="author">
            <collab>American College of Emergency PhysiciansSociety for Cardiovascular Angiography and Interventions</collab>
          </person-group>
          <article-title>2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2013</year>
          <volume>61</volume>
          <issue>4</issue>
          <fpage>e78</fpage>
          <lpage>140</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2012.11.019</pub-id>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17 Wald DS, Morris JK, Wald NJ, Chase AJ, Edwards RJ, Hughes LO, et al; PRAMI Investigators. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med. 2013;369(12):1115-23. doi: 10.1056/NEJMoa1305520.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wald</surname>
              <given-names>DS</given-names>
            </name>
            <name>
              <surname>Morris</surname>
              <given-names>JK</given-names>
            </name>
            <name>
              <surname>Wald</surname>
              <given-names>NJ</given-names>
            </name>
            <name>
              <surname>Chase</surname>
              <given-names>AJ</given-names>
            </name>
            <name>
              <surname>Edwards</surname>
              <given-names>RJ</given-names>
            </name>
            <name>
              <surname>Hughes</surname>
              <given-names>LO</given-names>
            </name>
            <etal/>
            <collab>PRAMI Investigators</collab>
          </person-group>
          <article-title>Randomized trial of preventive angioplasty in myocardial infarction</article-title>
          <source>N Engl J Med</source>
          <year>2013</year>
          <volume>369</volume>
          <issue>12</issue>
          <fpage>1115</fpage>
          <lpage>1123</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJMoa1305520</pub-id>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18 Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA., Cercek B, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial Infarction: An update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv. 2016;87(6):1001-19. doi: 10.1002/ccd.26325.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Levine</surname>
              <given-names>GN</given-names>
            </name>
            <name>
              <surname>Bates</surname>
              <given-names>ER</given-names>
            </name>
            <name>
              <surname>Blankenship</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Bailey</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Bittl</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Cercek</surname>
              <given-names>B</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial Infarction An update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions</article-title>
          <source>Catheter Cardiovasc Interv</source>
          <year>2016</year>
          <volume>87</volume>
          <issue>6</issue>
          <fpage>1001</fpage>
          <lpage>1019</lpage>
          <pub-id pub-id-type="doi">10.1002/ccd.26325</pub-id>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19 Piegas LS, Timerman A, Feitosa GS, Nicolau JC, Mattos LA, Andrade MD, et al. V Diretriz da Sociedade Brasileira de Cardiologia sobre tratamento do infarto agudo do mioc&#225;rdio com supradesn&#237;vel do segmento ST. Arq Bras Cardiol. 2015;105(2):1-105. doi: http://dx.doi.org/10.5935/abc.20150107.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Piegas</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Timerman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Feitosa</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Nicolau</surname>
              <given-names>JC</given-names>
            </name>
            <name>
              <surname>Mattos</surname>
              <given-names>LA</given-names>
            </name>
            <name>
              <surname>Andrade</surname>
              <given-names>MD</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>V Diretriz da Sociedade Brasileira de Cardiologia sobre tratamento do infarto agudo do mioc&#225;rdio com supradesn&#237;vel do segmento ST</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2015</year>
          <volume>105</volume>
          <issue>2</issue>
          <fpage>1</fpage>
          <lpage>105</lpage>
          <pub-id pub-id-type="doi">10.5935/abc.20150107</pub-id>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20 Politi L, Sgura F, Rossi R, Monopoli D, Guerri E, Leuzzi C, et al. A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up. Heart. 2010;96(9):662-7. doi: 10.1136/hrt.2009.177162. Erratum in: Heart. 2014;100(4):350</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Politi</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Sgura</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Rossi</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Monopoli</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Guerri</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Leuzzi</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up</article-title>
          <source>Heart</source>
          <year>2010</year>
          <volume>96</volume>
          <issue>9</issue>
          <fpage>662</fpage>
          <lpage>667</lpage>
          <pub-id pub-id-type="doi">10.1136/hrt.2009.177162</pub-id>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21 Gershlick AH, Blackman DJ, Dalby M, Fairbrother KL, Banya W, Ms C, et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease (The CvLPRIT Trial). J Am Coll Cardiol. 2015;65(10):963-72. doi: 10.1016/j.jacc.2014.12.038.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gershlick</surname>
              <given-names>AH</given-names>
            </name>
            <name>
              <surname>Blackman</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Dalby</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Fairbrother</surname>
              <given-names>KL</given-names>
            </name>
            <name>
              <surname>Banya</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Ms</surname>
              <given-names>C</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease (The CvLPRIT Trial)</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2015</year>
          <volume>65</volume>
          <issue>10</issue>
          <fpage>963</fpage>
          <lpage>972</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2014.12.038</pub-id>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>22 Engstrom T, Kelbaek H, Helqvist S, Hofsten DE, Klovgaard L, Holmvang L, et al; DANAMI-3-PRIMULTI Investigators. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3 - PRIMULTI): An open-label, randomised controlled trial. Lancet. 2015;386(9994):665-71. PMID: 26347918.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Engstrom</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Kelbaek</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Helqvist</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Hofsten</surname>
              <given-names>DE</given-names>
            </name>
            <name>
              <surname>Klovgaard</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Holmvang</surname>
              <given-names>L</given-names>
            </name>
            <etal/>
            <collab>DANAMI-3-PRIMULTI Investigators</collab>
          </person-group>
          <article-title>Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3 - PRIMULTI): An open-label, randomised controlled trial</article-title>
          <source>Lancet</source>
          <year>2015</year>
          <volume>386</volume>
          <issue>9994</issue>
          <fpage>665</fpage>
          <lpage>671</lpage>
          <pub-id pub-id-type="pmid">26347918</pub-id>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>23 Pandit A, Aryal MR, Aryal Pandit A, Hakim FA, Giri S, Mainali NR, et al. Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis. Open Heart. 2014;1(1):e000012. doi: 10.1136/openhrt-2013-000012.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pandit</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Aryal</surname>
              <given-names>MR</given-names>
            </name>
            <name>
              <surname>Aryal Pandit</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Hakim</surname>
              <given-names>FA</given-names>
            </name>
            <name>
              <surname>Giri</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Mainali</surname>
              <given-names>NR</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI a systematic review and meta-analysis</article-title>
          <source>Open Heart</source>
          <year>2014</year>
          <volume>1</volume>
          <issue>1</issue>
          <elocation-id>e000012</elocation-id>
          <pub-id pub-id-type="doi">10.1136/openhrt-2013-000012</pub-id>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>24 Spencer FA, Sekercioglu N, Prasad M, Lopes LC, Guyatt GH. Culprit vessel versus immediate complete revascularization in patients with ST-segment myocardial infarction - A systematic review. Am Heart J. 2015;170(6):1133-9. doi: 10.1016/j.ahj.2015.09.002.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Spencer</surname>
              <given-names>FA</given-names>
            </name>
            <name>
              <surname>Sekercioglu</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Prasad</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Lopes</surname>
              <given-names>LC</given-names>
            </name>
            <name>
              <surname>Guyatt</surname>
              <given-names>GH</given-names>
            </name>
          </person-group>
          <article-title>Culprit vessel versus immediate complete revascularization in patients with ST-segment myocardial infarction - A systematic review</article-title>
          <source>Am Heart J</source>
          <year>2015</year>
          <volume>170</volume>
          <issue>6</issue>
          <fpage>1133</fpage>
          <lpage>1139</lpage>
          <pub-id pub-id-type="doi">10.1016/j.ahj.2015.09.002</pub-id>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25 Tarantini G, D'Amico G, Brener SJ, Tellaroli P, Basile M, Schiavo A, et al. Survival after varying revascularization strategies in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: a pairwise and network meta-analysis. JACC Cardiovasc Interv. 2016;9(17):1765-76. doi: 10.1016/j.jcin.2016.06.012.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Tarantini</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>D'Amico</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Brener</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>Tellaroli</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Basile</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Schiavo</surname>
              <given-names>A</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Survival after varying revascularization strategies in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: a pairwise and network meta-analysis</article-title>
          <source>JACC Cardiovasc Interv</source>
          <year>2016</year>
          <volume>9</volume>
          <issue>17</issue>
          <fpage>1765</fpage>
          <lpage>1776</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jcin.2016.06.012</pub-id>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>26 Smits PC, Abdel-Wahab M, Neumann F-J, Boxma-de Klerk BM, Lunde K, Schotborgh CE, et al. Fractional flow reserve-guided multivessel angioplasty in myocardial infarction. N Engl J Med. 2017;376(13):1234-1244. doi: 10.1056/NEJMoa1701067.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Smits</surname>
              <given-names>PC</given-names>
            </name>
            <name>
              <surname>Abdel-Wahab</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Neumann</surname>
              <given-names>F-J</given-names>
            </name>
            <name>
              <surname>Boxma-de Klerk</surname>
              <given-names>BM</given-names>
            </name>
            <name>
              <surname>Lunde</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Schotborgh</surname>
              <given-names>CE</given-names>
            </name>
            <etal/>
          </person-group>
          <article-title>Fractional flow reserve-guided multivessel angioplasty in myocardial infarction</article-title>
          <source>N Engl J Med</source>
          <year>2017</year>
          <volume>376</volume>
          <issue>13</issue>
          <fpage>1234</fpage>
          <lpage>1244</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJMoa1701067</pub-id>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>27 U.S. National Library of Medicine. Clinical trials gov. Complete vs. Culprit-only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI (COMPLETE). December 04, 2012. [Accessed on 2016 May 10]. Updated March 23, 2015. Available from: <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01740479">https://clinicaltrials.gov/ct2/show/NCT01740479</ext-link>.</mixed-citation>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>U.S. National Library of Medicine</collab>
            <collab>Clinical trials gov</collab>
          </person-group>
          <source>Complete vs. Culprit-only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI (COMPLETE)</source>
          <day>04</day>
          <month>12</month>
          <year>2012</year>
          <date-in-citation content-type="access-date">2016 May 10</date-in-citation>
          <date-in-citation content-type="updated">March 23, 2015</date-in-citation>
          <comment>Available from: <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT01740479">https://clinicaltrials.gov/ct2/show/NCT01740479</ext-link>
					</comment>
        </element-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <mixed-citation>28 U.S. National Library of Medicine. Clinical trials gov. FFR Versus Angiography-Guided Strategy for Management of STEMI With Multivessel Disease (FRAME-STEMI). March 22, 2016. [Accessed on 2016 Sep 16]. Uptaded June 10, 2016. Available at: <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/study/NCT02715518">https://clinicaltrials.gov/ct2/show/study/NCT02715518</ext-link>.</mixed-citation>
        <element-citation publication-type="book">
          <person-group person-group-type="author">
            <collab>U.S. National Library of Medicine</collab>
            <collab>Clinical trials gov</collab>
          </person-group>
          <source>FFR Versus Angiography-Guided Strategy for Management of STEMI With Multivessel Disease (FRAME-STEMI)</source>
          <day>22</day>
          <month>03</month>
          <year>2016</year>
          <date-in-citation content-type="access-date">2016 Sep 16</date-in-citation>
          <date-in-citation content-type="updated">June 10, 2016</date-in-citation>
          <comment>Available at: <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/study/NCT02715518">https://clinicaltrials.gov/ct2/show/study/NCT02715518</ext-link>
					</comment>
        </element-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <mixed-citation>29 Bhatt DL. Do we really know the CvLPRIT in myocardial infarction? or just stent all lesions? J Am Coll Cardiol. 2015;65(10):973-5. doi: 10.1016/j.jacc.2014.12.037.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bhatt</surname>
              <given-names>DL</given-names>
            </name>
          </person-group>
          <article-title>Do we really know the CvLPRIT in myocardial infarction? or just stent all lesions?</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2015</year>
          <volume>65</volume>
          <issue>10</issue>
          <fpage>973</fpage>
          <lpage>975</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2014.12.037</pub-id>
        </element-citation>
      </ref>
      <ref id="B30">
        <label>30</label>
        <mixed-citation>30 Di Mario C, Rosser G. Open questions for non-infarct-related arteries in STEMI. Lancet. 2015;386(9994):630-2. PMID: 26347917.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Di Mario</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Rosser</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>Open questions for non-infarct-related arteries in STEMI</article-title>
          <source>Lancet</source>
          <year>2015</year>
          <volume>386</volume>
          <issue>9994</issue>
          <fpage>630</fpage>
          <lpage>632</lpage>
          <pub-id pub-id-type="pmid">26347917</pub-id>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo de Revis&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Interven&#231;&#227;o Percut&#226;nea no Infarto com Supradesnivelamento do Segmento ST: Revasculariza&#231;&#227;o Completa ou Tratamento apenas da Art&#233;ria Culpada?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Os&#243;rio</surname>
            <given-names>Ana Paula Susin</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Quadros</surname>
            <given-names>Alexandre Schaan de</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Jos&#233; Luiz da Costa</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Portal</surname>
            <given-names>Vera Lucia</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <institution content-type="original">Instituto de Cardiologia/Funda&#231;&#227;o Universit&#225;ria de Cardiologia (IC/FUC), Porto Alegre, RS - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Vera Lucia Portal &#8226;</bold> Rua Luciana de Abreu, 471, sala 603. CEP 90570-080, Moinhos de Vento, Porto Alegre, RS - Brasil. E-mail: <email>vera.portal@hotmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa e Obten&#231;&#227;o de dados: Os&#243;rio APS, Vieira JLC, Portal VL; An&#225;lise e interpreta&#231;&#227;o dos dados, Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Os&#243;rio APS, Quadros AS, Vieira JLC, Portal VL.</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>
        <p>O adequado manejo da doen&#231;a arterial coronariana (DAC) multivascular, no contexto do infarto agudo do mioc&#225;rdio com supradesnivelamento do segmento ST e da interven&#231;&#227;o coronariana percut&#226;nea prim&#225;ria, &#233; um dos grandes motivos de controv&#233;rsia em Cardiologia. Embora as principais diretrizes mundiais n&#227;o recomendem a revasculariza&#231;&#227;o completa de forma rotineira nesses pacientes, recentes ensaios cl&#237;nicos randomizados (ECRs) t&#234;m demonstrado benef&#237;cio dessa abordagem na redu&#231;&#227;o de desfechos cardiovasculares. Por esse motivo, torna-se imprescind&#237;vel uma adequada revis&#227;o dessas evid&#234;ncias, a fim de que se possa estabelecer uma conduta cientificamente embasada e capaz de trazer benef&#237;cios aos pacientes que se apresentam no contexto agudo do infarto do mioc&#225;rdio. Esta revis&#227;o objetivou apresentar de forma objetiva as evid&#234;ncias mais recentes dispon&#237;veis a respeito desse tema.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Infarto do Mioc&#225;rdio</kwd>
        <kwd>Revasculariza&#231;&#227;o Mioc&#225;rdica</kwd>
        <kwd>Interven&#231;&#227;o Coron&#225;ria Percut&#226;nea</kwd>
        <kwd>Doen&#231;a da Art&#233;ria Coronariana</kwd>
        <kwd>Stents</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A interven&#231;&#227;o coronariana percut&#226;nea prim&#225;ria (ICPp) representa, atualmente, o tratamento de escolha para o infarto agudo do mioc&#225;rdio com supradesnivelamento do segmento ST (IAMCSSST).<xref ref-type="bibr" rid="B1">1</xref> Entretanto, apesar de seu incontest&#225;vel benef&#237;cio, algumas quest&#245;es relacionadas &#224; sua adequada aplica&#231;&#227;o ainda s&#227;o motivo de controv&#233;rsia.</p>
        <p>Aproximadamente de 40 a 50% dos pacientes que se apresentam com IAMCSSST possuem doen&#231;a arterial coronariana (DAC) multivascular,<xref ref-type="bibr" rid="B2">2</xref> embora a maioria desses indiv&#237;duos seja assintom&#225;tica at&#233; a manifesta&#231;&#227;o aguda.<xref ref-type="bibr" rid="B3">3</xref> Sabe-se que, quando comparados com portadores de DAC com acometimento de um &#250;nico vaso, eles possuem maior taxa de mortalidade e maior incid&#234;ncia de reinfarto n&#227;o fatal.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref> Dados brasileiros, provenientes do Instituto de Cardiologia do Rio Grande do Sul, mostram que em um total de 2.469 pacientes atendidos por IAMCSSST durante o per&#237;odo de 2010 a 2014, cerca de 30% possu&#237;am acometimento de dois vasos, e 20%, de tr&#234;s vasos. Em an&#225;lise multivariada, a DAC de tr&#234;s vasos mostrou ser forte preditor de mortalidade em 30 dias (OR 3,39; IC95% 1,47-3,87; p &lt; 0,001).<xref ref-type="bibr" rid="B6">6</xref>
				</p>
        <p>O progn&#243;stico em longo prazo do infarto agudo do mioc&#225;rdio (IAM) associado &#224; DAC multivascular &#233; pior provavelmente em raz&#227;o de uma s&#233;rie de mecanismos patol&#243;gicos, como: instabilidade adicional de outras placas ateroscler&#243;ticas; preju&#237;zo na perfus&#227;o mioc&#225;rdica causada por disfun&#231;&#227;o endotelial; espasmo microvascular ou inflama&#231;&#227;o; e redu&#231;&#227;o de contratilidade em zonas n&#227;o infartadas. Os piores desfechos em longo prazo tamb&#233;m podem ser atribu&#237;dos &#224; idade mais elevada dos pacientes, mais fatores de risco para aterosclerose e &#224; menor fun&#231;&#227;o ventricular esquerda em indiv&#237;duos com DAC multivascular.<xref ref-type="bibr" rid="B7">7</xref> O benef&#237;cio da revasculariza&#231;&#227;o multiarterial nesse contexto poderia estar relacionado a diminui&#231;&#227;o do risco de novas oclus&#245;es coronarianas, diminui&#231;&#227;o da carga isqu&#234;mica total e melhora do potencial para circula&#231;&#227;o colateral.</p>
        <p>Surge, dessa maneira, um importante questionamento em rela&#231;&#227;o a melhor estrat&#233;gia de ICPp nesses indiv&#237;duos: o tratamento apenas da les&#227;o culpada pelo IAM ou a revasculariza&#231;&#227;o completa, com angioplastia de estenoses em art&#233;rias n&#227;o relacionadas ao IAM. </p>
        <p>Metan&#225;lises de estudos observacionais, em sua maioria registros, t&#234;m demonstrado resultados conflitantes quando a ICP &#233; realizada em art&#233;rias n&#227;o culpadas pelo IAM.<xref ref-type="bibr" rid="B8">8</xref><sup>-</sup><xref ref-type="bibr" rid="B10">10</xref>
				</p>
        <p>Cavender et al.<xref ref-type="bibr" rid="B8">8</xref> reuniram dados provenientes do <italic>National Cardiovascular Data Registry</italic>, registro americano de 708.481 admiss&#245;es hospitalares durante os anos de 2004 a 2007, com o objetivo de determinar preval&#234;ncia, preditores e desfechos intra-hospitalares da revasculariza&#231;&#227;o completa no IAM. Os pacientes submetidos &#224; abordagem multivascular apresentavam maior gravidade, com incid&#234;ncia mais elevada de choque cardiog&#234;nico, insufici&#234;ncia card&#237;aca (IC), fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda menor que 30% e comprometimento da art&#233;ria descendente anterior proximal. A mortalidade intra-hospitalar foi maior naqueles submetidos &#224; revasculariza&#231;&#227;o completa (7,9% <italic>versus</italic> 5,1%; p &lt; 0,01). Os pacientes em choque cardiog&#234;nico que receberam ICP de art&#233;rias n&#227;o culpadas pelo IAM tamb&#233;m tiveram maior mortalidade (36,5% <italic>versus</italic> 27,8%; OR 1,54; IC95% 1,22-1,95).</p>
        <p>J&#225; Bangalore et al.<xref ref-type="bibr" rid="B9">9</xref> reuniram dados de 19 estudos (61.764 pacientes) que avaliaram IAM e DAC multivascular, com o objetivo de comparar desfechos precoces (&lt; 30 dias) e tardios em pacientes submetidos &#224; ICP apenas da art&#233;ria culpada ou revasculariza&#231;&#227;o completa. Dos 19 estudos, apenas 2 eram randomizados. Foram exclu&#237;dos os pacientes submetidos &#224; estrat&#233;gia estagiada. N&#227;o houve diferen&#231;a significativa nos desfechos precoces de mortalidade, IAM, acidente vascular cerebral (AVC) e revasculariza&#231;&#227;o de vaso alvo. Em longo prazo (2 &#177; 1,1 anos) tamb&#233;m n&#227;o houve diferen&#231;a na mortalidade, IAM, AVC, revasculariza&#231;&#227;o de vaso alvo e trombose de <italic>stent</italic>, por&#233;m foram encontradas redu&#231;&#245;es de 33% na mortalidade, 43% na necessidade de nova interven&#231;&#227;o percut&#226;nea e 53% na cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica. Encontrou-se redu&#231;&#227;o significativa de eventos cardiovasculares adversos quando utilizada a estrat&#233;gia de revasculariza&#231;&#227;o completa, em compara&#231;&#227;o com abordagem apenas da art&#233;ria culpada (OR 0,60; IC95% 0,50-0,72).</p>
        <p>Em metan&#225;lise de 11 estudos, Sethi et al.<xref ref-type="bibr" rid="B10">10</xref> compararam os desfechos de 4.640 pacientes submetidos &#224; revasculariza&#231;&#227;o completa durante o procedimento da ICPp ou na mesma interna&#231;&#227;o com 27.394 pacientes tratados apenas com ICP da art&#233;ria culpada pelo IAM. Apenas 2 eram ensaios cl&#237;nicos randomizados (ECRs), 8 eram estudos observacionais e 1 era caso-controle. A maioria dos pacientes encontrava-se hemodinamicamente est&#225;vel. N&#227;o houve diferen&#231;a em rela&#231;&#227;o a eventos cardiovasculares maiores (OR 0,95; IC95% 0,47-1,90) e &#224; mortalidade em longo prazo (OR 1,10; IC95% 0,76-1,59). Havia heterogeneidade entre os estudos, al&#233;m de aus&#234;ncia de estudos com desenho espec&#237;fico para responder a essa quest&#227;o.</p>
        <p>Duas grandes metan&#225;lises de estudos observacionais,<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> com mais de 40.000 pacientes cada, relataram que a abordagem completa durante o procedimento de ICPp foi associado com maior mortalidade, enquanto a interven&#231;&#227;o estagiada (realizada mais tardiamente durante a interna&#231;&#227;o ou ap&#243;s 30 dias do evento agudo) associou-se &#224; redu&#231;&#227;o de mortalidade. J&#225; pequenos ECRs n&#227;o mostraram melhora em desfechos ou progn&#243;stico em pacientes tratados com revasculariza&#231;&#227;o completa no contexto agudo.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref>
				</p>
        <p>Em metan&#225;lise pareada e em rede, envolvendo 4 estudos prospectivos e 14 retrospectivos com um total de 40.280 pacientes, Vlaar e et al.<xref ref-type="bibr" rid="B11">11</xref> avaliaram tr&#234;s estrat&#233;gias de revasculariza&#231;&#227;o: 1) ICP apenas da art&#233;ria culpada pelo IAM; 2) revasculariza&#231;&#227;o completa imediata de uma ou mais art&#233;rias n&#227;o relacionadas ao IAM; 3) revasculariza&#231;&#227;o estagiada durante interna&#231;&#227;o hospitalar de uma ou mais art&#233;rias n&#227;o relacionadas ao IAM. Na an&#225;lise pareada, observou-se que revasculariza&#231;&#227;o estagiada associou-se &#224; menor mortalidade em curto e longo prazo, quando comparada com ICP apenas da art&#233;ria culpada ou revasculariza&#231;&#227;o completa imediata. Revasculariza&#231;&#227;o completa imediata teve maiores taxas de mortalidade em curto e longo prazo. J&#225; na metan&#225;lise em rede, revasculariza&#231;&#227;o estagiada associou-se de forma consistente &#224; menor mortalidade.</p>
        <p>De forma semelhante, Bainey et al.<xref ref-type="bibr" rid="B12">12</xref> realizaram revis&#227;o sistem&#225;tica e metan&#225;lise de 26 estudos (46.324 pacientes) comparando estrat&#233;gias de revasculariza&#231;&#227;o pra DAC multivascular no IAM. Apenas 3 estudos eram randomizados. N&#227;o houve diferen&#231;a em mortalidade hospitalar, quando comparada &#224; ICP apenas da art&#233;ria culpada com revasculariza&#231;&#227;o completa, por&#233;m houve aumento dessa mortalidade quando a abordagem das outras art&#233;rias era realizada durante o mesmo procedimento da ICPp. Redu&#231;&#227;o de mortalidade hospitalar foi observada com revasculariza&#231;&#227;o completa estagiada. Com a estrat&#233;gia de revasculariza&#231;&#227;o completa, houve redu&#231;&#227;o de mortalidade em longo prazo e de necessidade de novas interven&#231;&#245;es.</p>
        <sec>
          <title>Recomenda&#231;&#245;es das diretrizes</title>
          <p>As principais diretrizes que abordam o tratamento do IAMCSSST t&#234;m desencorajado a ICP de art&#233;rias n&#227;o culpadas pelo IAM. De acordo com o <italic>ESC Guidelines for the Management of Acute Myocardial Infarction in Patients Presenting with ST-Segment Elevation</italic>,<xref ref-type="bibr" rid="B15">15</xref> publicado em 2012 pela Sociedade Europeia de Cardiologia, n&#227;o existe evid&#234;ncia para interven&#231;&#227;o de emerg&#234;ncia em les&#245;es n&#227;o culpadas pelo IAM. A abordagem da DAC multivascular durante a ICPp s&#243; &#233; justificada em casos de choque cardiog&#234;nico com presen&#231;a de m&#250;ltiplas estenoses cr&#237;ticas ou de les&#245;es altamente inst&#225;veis (sinais angiogr&#225;ficos de trombos ou ruptura de les&#227;o) ou de evid&#234;ncia de isquemia persistente a despeito da angioplastia da art&#233;ria culpada.</p>
          <p>J&#225; a diretriz norte-americana, publicada em 2013 (<italic>2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction</italic>),<xref ref-type="bibr" rid="B16">16</xref> considerava como classe III (causador de dano) a angioplastia de art&#233;rias n&#227;o culpadas pelo IAM, no contexto da ICPp em pacientes sem comprometimento hemodin&#226;mico. Por&#233;m, ap&#243;s o surgimento de novas evid&#234;ncias, principalmente ap&#243;s a publica&#231;&#227;o do estudo PRAMI,<xref ref-type="bibr" rid="B17">17</xref> em 2013, foi divulgada uma atualiza&#231;&#227;o dessa diretriz, passando a ser considerada como classe IIb a angioplastia da art&#233;ria n&#227;o culpada no momento da ICPp ou como procedimento estagiado antes da alta hospitalar.<xref ref-type="bibr" rid="B18">18</xref>
					</p>
          <p>Mais recentemente, a diretriz brasileira (<italic>V Diretriz da Sociedade Brasileira de Cardiologia sobre Tratamento do Infarto Agudo do Mioc&#225;rdio com Supradesn&#237;vel do Segmento ST</italic>), publicada em 2015, recomenda que a abordagem percut&#226;nea deve ser dedicada &#224; art&#233;ria culpada pelo IAM. A revasculariza&#231;&#227;o imediata de outras art&#233;rias n&#227;o culpadas pelo evento &#237;ndice durante a ICP prim&#225;ria pode ser considerada em pacientes selecionados, como em casos de estenose grave de menor complexidade localizada no mesmo sistema coron&#225;rio relacionado ao vaso infartado e de acordo com criteriosa avalia&#231;&#227;o da situa&#231;&#227;o cl&#237;nica e hemodin&#226;mica do paciente (IIb,B).<xref ref-type="bibr" rid="B19">19</xref>
					</p>
        </sec>
        <sec>
          <title>Principais estudos</title>
          <p>Um dos primeiros ECRs a abordar o tema foi conduzido em um centro italiano por Politi et al. Foram inclu&#237;dos 214 pacientes consecutivos com IAM e DAC multivascular no contexto de ICPp. Doen&#231;a multivascular foi definida como presen&#231;a de estenose maior do que 70% em duas ou mais coron&#225;rias epic&#225;rdicas ou em seus ramos principais, em avalia&#231;&#227;o angiogr&#225;fica visual. Antes da primeira angioplastia, os pacientes foram randomizados para tr&#234;s estrat&#233;gias principais: ICP apenas da art&#233;ria culpada, revasculariza&#231;&#227;o completa estagiada ou revasculariza&#231;&#227;o completa no momento da ICPp.<xref ref-type="bibr" rid="B20">20</xref>
					</p>
          <p>O desfecho prim&#225;rio considerado foi composto de eventos card&#237;acos maiores, definido por: morte card&#237;aca e n&#227;o card&#237;aca, mortalidade intra-hospitalar, reinfarto, reinterna&#231;&#227;o hospitalar por s&#237;ndrome coronariana aguda e necessidade de nova revasculariza&#231;&#227;o. Ap&#243;s seguimento de 2,5 anos, pelo menos um evento card&#237;aco maior foi identificado em 42 (50%) dos pacientes tratados apenas com ICP da art&#233;ria culpada, em 13 (20%) do grupo de revasculariza&#231;&#227;o completa estagiada e em 15 (23,1%) dos submetidos &#224; revasculariza&#231;&#227;o completa durante ICPp, mostrando diferen&#231;a significativa (p &lt; 0,001). Morte intra-hospitalar, necessidade de novas revasculariza&#231;&#245;es e reinterna&#231;&#227;o ocorreram mais frequentemente nos tratados com ICP apenas da art&#233;ria culpada. N&#227;o houve diferen&#231;a em rela&#231;&#227;o &#224; mortalidade entre os tr&#234;s grupos.</p>
          <p>O estudo PRAMI <italic>- Randomized Trial of Preventive Angioplasty in Myocardial Infarction,</italic><xref ref-type="bibr" rid="B17">17</xref> publicado em 2013, foi o primeiro ECR de maior magnitude a comparar a angioplastia apenas da art&#233;ria culpada pelo IAM com a revasculariza&#231;&#227;o completa de les&#245;es em outras art&#233;rias n&#227;o culpadas durante o procedimento &#237;ndice. Nesse estudo, conduzido de forma aberta, foram randomizados 465 pacientes submetidos &#224; ICPp. Nos pacientes alocados para revasculariza&#231;&#227;o completa, eram tratadas todas as estenoses angiograficamente maiores que 50% no mesmo procedimento da ICPp. O desfecho prim&#225;rio considerado foi um composto de morte por todas as causas, IAM n&#227;o fatal ou angina refrat&#225;ria. Ap&#243;s um seguimento m&#233;dio de 23 meses, o estudo foi interrompido precocemente em raz&#227;o de uma diferen&#231;a altamente significativa entre os grupos. Houve redu&#231;&#227;o de 65% no desfecho prim&#225;rio no grupo submetido &#224; revasculariza&#231;&#227;o completa durante a ICPp (HR 0,35; IC95% 0,21-0,58; p &lt; 0,001). Redu&#231;&#227;o semelhante tamb&#233;m foi encontrada quando analisado o desfecho prim&#225;rio composto por morte de causa card&#237;aca ou IAM n&#227;o fatal (HR 0,36; IC95% 0,18-0,73). O grupo submetido &#224; revasculariza&#231;&#227;o completa apresentou maiores tempo de procedimento e de volume de contraste, entretanto as taxas de complica&#231;&#245;es, incluindo acidente vascular cerebral, sangramento e nefropatia induzida por contraste foram semelhantes entre os grupos.</p>
          <p>Esse foi um estudo de angioplastia preventiva, tratando as outras les&#245;es presentes acima de 50%, al&#233;m da coron&#225;ria culpada sem se preocupar se elas estavam ocasionando limita&#231;&#227;o de fluxo. Cr&#237;ticas a esse estudo apontam o desenho n&#227;o cegado como uma falha, pois os pacientes estavam cientes de que tinham les&#245;es n&#227;o tratadas, tornando os achados suscet&#237;veis a vi&#233;s. Al&#233;m disso, os pacientes do grupo controle n&#227;o foram testados para a presen&#231;a de isquemia ocasionada pelas les&#245;es residuais, sendo investigados e tratados apenas se apresentassem angina refrat&#225;ria. Quando comparado a outros estudos que abordaram a mesma quest&#227;o, ressalta-se que n&#227;o foi avaliada a revasculariza&#231;&#227;o completa de forma estagiada em momento diferente da ICPp.</p>
          <p>Posteriormente, o estudo CvLPRIT <italic>- Complete</italic> versus <italic>Lesion-only Primary PCI Trial</italic>,<xref ref-type="bibr" rid="B21">21</xref> ECR, aberto, multic&#234;ntrico, conduzido em sete centros no Reino Unido, foi publicado em 2015. Foram randomizados 296 pacientes com IAMCSSST para ICP da art&#233;ria culpada ou revasculariza&#231;&#227;o completa na admiss&#227;o &#237;ndice. A aloca&#231;&#227;o nos grupos era realizada ap&#243;s angiografia com estenoses maior do que 50% em art&#233;rias n&#227;o culpadas pelo IAM. A revasculariza&#231;&#227;o completa deveria ser feita no mesmo procedimento, mas o operador poderia optar pelo procedimento em outro momento antes da alta hospitalar, incluindo, dessa maneira, a estrat&#233;gia de revasculariza&#231;&#227;o estagiada.</p>
          <p>Ap&#243;s um seguimento m&#233;dio de 12 meses, houve redu&#231;&#227;o significativa (55%) no desfecho prim&#225;rio composto por mortalidade, IAM recorrente, IC ou revasculariza&#231;&#227;o guiada por isquemia (10% <italic>versus</italic> 21%; HR 0,45; p = 0,009) nos pacientes submetidos &#224; revasculariza&#231;&#227;o completa. A redu&#231;&#227;o do desfecho prim&#225;rio foi evidente precocemente, dentro dos primeiros 30 dias de seguimento, embora de forma n&#227;o significativa (p = 0,055).</p>
          <p>Dos 150 pacientes alocados para a revasculariza&#231;&#227;o completa, 64% foram tratados durante o mesmo procedimento da ICPp, subgrupo no qual se observou uma tend&#234;ncia a maior benef&#237;cio. Ressalta-se, por&#233;m, que o estudo n&#227;o teve desenho espec&#237;fico para esse tipo de an&#225;lise.</p>
          <p>Como esperado, os pacientes submetidos &#224; revasculariza&#231;&#227;o completa tiveram um n&#250;mero maior de <italic>stents</italic> implantados, assim como maior tempo de procedimento e de volume de contraste utilizado. Os desfechos de seguran&#231;a considerados, incluindo AVC, sangramento maior e nefropatia induzida por contraste, foram similares entre os grupos.</p>
          <p>Cabe ressaltar que, embora resultados positivos tenham sido encontrados, o <italic>CvLPRIT Trial</italic> n&#227;o tinha poder estat&#237;stico suficiente para detectar diferen&#231;as em importantes componentes do desfecho prim&#225;rio, como morte e IAM.</p>
          <p>Ainda, na tentativa de uma resposta em rela&#231;&#227;o ao melhor manejo da DAC multivascular no contexto da ICPp, Engstrom et al. conduziram o estudo <italic>DANAMI3-PRIMULTI</italic>,<xref ref-type="bibr" rid="B22">22</xref> publicado em 2015. Nesse ECR e aberto, comparou-se uma estrat&#233;gia de revasculariza&#231;&#227;o completa guiada por reserva fracionada de fluxo (FFR) dois dias ap&#243;s o procedimento &#237;ndice com nenhuma interven&#231;&#227;o adicional ap&#243;s a ICPp. Foram randomizados 627 pacientes em dois centros na Dinamarca, sendo considerado como desfecho prim&#225;rio um composto de mortalidade por todas as causas, reinfarto ou revasculariza&#231;&#227;o guiada por isquemia (subjetiva ou objetiva) de art&#233;rias n&#227;o relacionadas ao IAM.</p>
          <p>Ap&#243;s seguimento de 27 meses, houve uma redu&#231;&#227;o significativa de 44% no desfecho prim&#225;rio analisado (HR 0,56; IC95% 0,38-0,83; p = 0,004) no grupo submetido &#224; ICP de art&#233;rias n&#227;o culpadas pelo IAM. Entretanto, quando analisadas individualmente, as taxas de mortalidade por todas as causas e de reinfarto foram semelhantes em ambos os grupos, enquanto o grupo da revasculariza&#231;&#227;o completa teve melhor resultado por conta da necessidade de menos reinterven&#231;&#245;es por angina refrat&#225;ria.</p>
          <p>Questiona-se, aqui, o real benef&#237;cio da revasculariza&#231;&#227;o completa, uma vez que n&#227;o houve diferen&#231;a em desfechos duros isolados, como mortalidade e reinfarto, e ao fato de que a redu&#231;&#227;o no desfecho prim&#225;rio deveu-se primariamente &#224; necessidade de novas revasculariza&#231;&#245;es.</p>
          <p>Em metan&#225;lise composta por tr&#234;s ECRs realizados at&#233; setembro de 2013, com total de 748 pacientes (416 randomizados para revasculariza&#231;&#227;o completa e 322 para ICP apenas da art&#233;ria culpada), Pandit et al. mostraram benef&#237;cios da ICP preventiva. No grupo tratado com revasculariza&#231;&#227;o completa durante ICPp, houve redu&#231;&#227;o significativa em morte cardiovascular (HR 0,39; IC95% 0,18-0,83; p = 0,01), necessidade de novas revasculariza&#231;&#245;es (OR 0,28; IC95% 0,18-0,44; p = 0,00001) e em IAM n&#227;o fatal (OR 0,38; IC95% 0,20-0,75; p = 0,005).<xref ref-type="bibr" rid="B23">23</xref>
					</p>
          <p>Spencer et al. conduziram outra metan&#225;lise, na qual foram inclu&#237;dos todos os ECR, at&#233; o ano de 2015, que compararam revasculariza&#231;&#227;o completa <italic>versus</italic> ICP apenas da art&#233;ria culpada no IAM. Foram inclu&#237;dos cinco ensaios cl&#237;nicos, com total de 1.568 pacientes. Revasculariza&#231;&#227;o completa associou-se &#224; redu&#231;&#227;o na necessidade de novas revasculariza&#231;&#245;es (RR 0,36; IC95% 0,27-0,49) e &#224; diminui&#231;&#227;o em IAM recorrente (RR 0,41; IC95% 0,30-0,57). Entretanto, quando considerada mortalidade total, n&#227;o houve diferen&#231;a significativa entre os grupos (RR 0,82; IC95% 0,53-1,26).<xref ref-type="bibr" rid="B24">24</xref>
					</p>
          <p>Tarantini et al. conduziram uma revis&#227;o sistem&#225;tica pareada e metan&#225;lise em rede com o objetivo de verificar qual a melhor estrat&#233;gia terap&#234;utica em pacientes com IAM com supradesnivelamento de segmento ST e DAC multivascular. Foram inclu&#237;dos estudos prospectivos e retrospectivos publicados entre 2001 e 2015. An&#225;lises foram realizadas para tr&#234;s estrat&#233;gias de interven&#231;&#227;o: 1) ICP apenas da art&#233;ria culpada; 2) revasculariza&#231;&#227;o completa durante o procedimento de ICPp; e 3) revasculariza&#231;&#227;o completa estagiada durante interna&#231;&#227;o hospitalar.<xref ref-type="bibr" rid="B25">25</xref> Foram inclu&#237;dos 32 estudos (13 prospectivos e 19 retrospectivos), com um total de 54.148 pacientes. A an&#225;lise pareada mostrou que revasculariza&#231;&#227;o completa estagiada associou-se &#224; menor mortalidade em curto e longo prazo, quando comparada com ICP apenas da art&#233;ria culpada e revasculariza&#231;&#227;o completa durante a ICPp. J&#225; a revasculariza&#231;&#227;o apenas da art&#233;ria culpada apresentou menor mortalidade em rela&#231;&#227;o &#224; revasculariza&#231;&#227;o completa durante o procedimento de ICPp. Em an&#225;lise em rede<italic>,</italic> revasculariza&#231;&#227;o completa estagiada associou-se de modo consistente &#224; melhora de sobrevida. Na <xref ref-type="table" rid="t2">Tabela 1</xref> est&#227;o descritos os principais achados dos ECR apresentados.</p>
          <table-wrap id="t2">
            <label>Tabela 1</label>
            <caption>
              <title>Principais caracter&#237;sticas dos ensaios cl&#237;nicos randomizados comparando interven&#231;&#227;o coronariana percut&#226;nea apenas da art&#233;ria culpada <italic>versus</italic> revasculariza&#231;&#227;o completa no infarto agudo do mioc&#225;rdio com supradesnivelamento do segmento ST</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">Estudo</th>
                  <th align="center">Tipo de estudo</th>
                  <th align="center">N</th>
                  <th align="center">ICP art&#233;rias n&#227;o culpadas</th>
                  <th align="center">Desfecho prim&#225;rio (composto)</th>
                  <th align="center">Resultado (desfecho prim&#225;rio)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Politi et al.</td>
                  <td align="center">ECR</td>
                  <td align="center">214</td>
                  <td align="center">Angiografia &gt; 70%</td>
                  <td align="center">Morte card&#237;aca e n&#227;o-card&#237;aca, morte intra-hospitalar, reinfarto, reinterna&#231;&#227;o por SCA, nova revasculariza&#231;&#227;o</td>
                  <td align="center">Redu&#231;&#227;o de eventos maiores com revasculariza&#231;&#227;o completa (p &lt; 0,001)</td>
                </tr>
                <tr>
                  <td align="left">PRAMI</td>
                  <td align="center">ECR</td>
                  <td align="center">465</td>
                  <td align="center">Angiografia &gt; 50%</td>
                  <td align="center">Morte por todas as causas, IAM n&#227;o fatal, angina refrat&#225;ria</td>
                  <td align="center">Redu&#231;&#227;o de 65% com revasculariza&#231;&#227;o completa (HR 0,35; IC95% 0,21-0,58; p &lt; 0,001)</td>
                </tr>
                <tr>
                  <td align="left">CvLPRIT</td>
                  <td align="center">ECR</td>
                  <td align="center">296</td>
                  <td align="center">Angiografia &gt; 50%</td>
                  <td align="center">Mortalidade, IAM recorrente, IC, revasculariza&#231;&#227;o guiada por isquemia</td>
                  <td align="center">Redu&#231;&#227;o de 55% com revasculariza&#231;&#227;o completa (10% <italic>vs</italic> 21%; HR 0,45; p = 0,009)</td>
                </tr>
                <tr>
                  <td align="left">DANAMI-3-PRIMULTI</td>
                  <td align="center">ECR</td>
                  <td align="center">627</td>
                  <td align="center">FFR &lt; 0,80</td>
                  <td align="center">Mortalidade por todas as causas, reinfarto, revasculariza&#231;&#227;o guiada por isquemia</td>
                  <td align="center">Redu&#231;&#227;o de 44% com revasculariza&#231;&#227;o completa (HR 0,56; IC95% 0,38-0,83; p = 0,004).</td>
                </tr>
                <tr>
                  <td align="left">COMPARE-ACUTE</td>
                  <td align="center">ECR</td>
                  <td align="center">885</td>
                  <td align="center">FFR &#8804; 0,80</td>
                  <td align="center">Mortalidade por todas as causas, IAM n&#227;o fatal, necessidade de qualquer revasculariza&#231;&#227;o, eventos cerebrovasculares</td>
                  <td align="center">Redu&#231;&#227;o de 65% com revasculariza&#231;&#227;o completa (HR 0,35; IC95% 0,22-0,55; p &lt; 0,001)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN2">
                <p>ECR: ensaio cl&#237;nico randomizado; HR: hazard ratio; IC: intervalo de confian&#231;a; SCA: s&#237;ndrome coronariana aguda.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <p>Recentemente, Smits et al. publicaram os resultados do ensaio cl&#237;nico multic&#234;ntrico <italic>Compare-Acute</italic>, no qual foram randomizados 885 pacientes com IAM e DAC multivascular submetidos &#224; ICPp. Esses pacientes foram comparados, em uma propor&#231;&#227;o de 1:2, para revasculariza&#231;&#227;o completa guiada por FFR ou ICP apenas da art&#233;ria culpada pelo IAM. Foram inclu&#237;dos pacientes com indica&#231;&#227;o para ICPp e que tivessem outras estenoses de, pelo menos, 50% em avalia&#231;&#227;o angiogr&#225;fica quantitativa ou visual. Todos os pacientes foram submetidos ao FFR, por&#233;m os que foram alocados para tratamento apenas da art&#233;ria culpada e seus m&#233;dicos assistentes n&#227;o eram informados sobre os resultados. No grupo randomizado para revasculariza&#231;&#227;o completa, ICP de art&#233;rias n&#227;o culpadas pelo IAM era realizada se FFR &#8804; 0,80, preferencialmente durante o mesmo procedimento da ICPp. O operador poderia optar pela revasculariza&#231;&#227;o completa em outro momento, desde que realizada durante a interna&#231;&#227;o hospitalar e em at&#233; 72 horas.<xref ref-type="bibr" rid="B26">26</xref>
					</p>
          <p>O desfecho prim&#225;rio considerado foi um composto de morte por todas as causas, IAM n&#227;o fatal, necessidade de qualquer revasculariza&#231;&#227;o e eventos cerebrovasculares em 12 meses. Ap&#243;s um ano, o desfecho prim&#225;rio ocorreu em 23 pacientes do grupo revasculariza&#231;&#227;o completa e em 121 daqueles tratados apenas com ICP da art&#233;ria culpada (HR 0,35; IC95% 0,22-0,55; p &lt; 0,001). N&#227;o houve diferen&#231;a significativa entre os grupos, quando analisados os desfechos isolados de morte por todas as causas e IAM. Houve redu&#231;&#227;o significativa na necessidade de novas revasculariza&#231;&#245;es no grupo da revasculariza&#231;&#227;o completa (HR 0,32; IC95% 0,20- 0,54; p &lt; 0,001). N&#227;o foram detectadas diferen&#231;as em rela&#231;&#227;o a desfechos de seguran&#231;a analisados.</p>
          <p>Embora com maior n&#250;mero de pacientes alocados e tamb&#233;m com a utiliza&#231;&#227;o de avalia&#231;&#227;o funcional com FFR, o estudo mostra novamente resultados positivos &#224;s custas de redu&#231;&#227;o na necessidade de novas revasculariza&#231;&#245;es. Desfechos duros, como morte e IAM, quando analisados de forma isolada, n&#227;o diferiram entre os grupos.</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Considerando os resultados dos estudos apresentados, a revasculariza&#231;&#227;o completa de art&#233;rias n&#227;o culpadas pelo IAM parece oferecer melhores resultados do que apenas o tratamento cl&#237;nico. Entretanto, deve-se salientar que ainda s&#227;o estudos com pequeno n&#250;mero de pacientes e com delineamento heterog&#234;neo, tendo sido utilizados diferentes crit&#233;rios para revasculariza&#231;&#227;o das estenoses n&#227;o culpadas, sejam eles angiogr&#225;ficos ou baseados em avalia&#231;&#227;o funcional, como o FFR. O pequeno n&#250;mero de eventos observados nos estudos dispon&#237;veis torna dif&#237;cil uma defini&#231;&#227;o quanto ao benef&#237;cio dessa estrat&#233;gia nas taxas de mortalidade e infarto recorrente.</p>
        <p>Metan&#225;lises e registros inicialmente publicados falharam em demonstrar claro benef&#237;cio da revasculariza&#231;&#227;o completa sobre a ICP apenas da art&#233;ria culpada. No estudo de Cavender et al.,<xref ref-type="bibr" rid="B8">8</xref> esse fato possivelmente est&#225; relacionado &#224; maior gravidade dos pacientes tratados com revasculariza&#231;&#227;o completa, a maioria com fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda reduzida ou em choque cardiog&#234;nico. Outro fator limitante dessas an&#225;lises iniciais &#233; a grande heterogeneidade dos estudos inclu&#237;dos, al&#233;m da aus&#234;ncia de desenhos espec&#237;ficos para avalia&#231;&#227;o de desfechos cardiovasculares maiores, como ocorre com o estudo de Sethi et al.<xref ref-type="bibr" rid="B10">10</xref> Por outro lado, metan&#225;lises mais recentes e com maior n&#250;mero de estudos, embora ainda em sua maioria observacionais, come&#231;am a apontar em favor do benef&#237;cio da revasculariza&#231;&#227;o completa, principalmente quando realizada de forma estagiada. Esse benef&#237;cio se confirma com a publica&#231;&#227;o dos principais ECRs que, apesar de suas limita&#231;&#245;es, possuem o desenho adequado para avalia&#231;&#227;o da melhor estrat&#233;gia.</p>
        <p>Outro ponto a ser considerado &#233; o momento apropriado para a realiza&#231;&#227;o da revasculariza&#231;&#227;o completa - durante o procedimento &#237;ndice ou de forma estagiada, na interna&#231;&#227;o. No estudo CvLPRIT, os pacientes tratados no procedimento &#237;ndice tiveram melhores resultados, apesar de o estudo n&#227;o ter sido desenhado para essa avalia&#231;&#227;o. J&#225; no DANAMI-3-PRIMULTI os pacientes foram revascularizados dois dias ap&#243;s o evento agudo, havendo redu&#231;&#227;o de desfechos, embora em raz&#227;o da necessidade de novas revasculariza&#231;&#245;es. Aspectos log&#237;sticos da realiza&#231;&#227;o de procedimentos multiarteriais em pacientes com IAMCSST devem especialmente ser considerados em nosso meio, j&#225; que esses pressup&#245;em equipe treinada, materiais dispon&#237;veis e <italic>backup</italic> cl&#237;nico e cir&#250;rgico, que podem n&#227;o estar dispon&#237;veis durante procedimentos realizados durante a madrugada, por exemplo.</p>
        <p>No momento, alguns ECRs est&#227;o em andamento na tentativa de elucidar qual a melhor estrat&#233;gia terap&#234;utica nesse contexto. Entre eles, est&#225; o estudo COMPLETE (<italic>Complete versus Culprit-only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI trial</italic>),<xref ref-type="bibr" rid="B27">27</xref> desenhado para detectar diferen&#231;as em morte cardiovascular ou IAM com revasculariza&#231;&#227;o completa estagiada <italic>versus</italic> ICP apenas da art&#233;ria culpada. H&#225; ainda o <italic>FRAME-STEMI trial</italic>, que avaliar&#225; estrat&#233;gias de revasculariza&#231;&#227;o guiadas com avalia&#231;&#227;o funcional (FFR) da les&#227;o em compara&#231;&#227;o &#224; avalia&#231;&#227;o angiogr&#225;fica tradicional.<xref ref-type="bibr" rid="B28">28</xref>
				</p>
        <p>Apesar dos achados dos &#250;ltimos ensaios cl&#237;nicos, ainda n&#227;o h&#225; uma resposta definitiva a respeito do melhor tratamento da DAC multivascular no contexto de IAMCSSST e ICPp.<xref ref-type="bibr" rid="B29">29</xref> Diversas particularidades devem ser consideradas na decis&#227;o sobre qual o melhor momento para abordagem das estenoses em art&#233;rias n&#227;o culpadas, entre elas, caracter&#237;sticas cl&#237;nicas do paciente, angiogr&#225;ficas da les&#227;o culpada e das art&#233;rias n&#227;o relacionadas. Por exemplo, pode ser mais prudente postergar a revasculariza&#231;&#227;o completa quando a angioplastia da les&#227;o culpada foi complexa, necessitou de um grande volume de contraste ou resultou em fluxo final n&#227;o satisfat&#243;rio. Da mesma maneira, les&#245;es complexas, como bifurca&#231;&#245;es, oclus&#245;es cr&#244;nicas, altamente calcificadas podem ser tratadas em um segundo momento.<xref ref-type="bibr" rid="B30">30</xref>
				</p>
        <p>As vantagens e desvantagens de cada estrat&#233;gia de interven&#231;&#227;o tamb&#233;m devem ser consideradas. A revasculariza&#231;&#227;o completa pode ser ben&#233;fica por permitir o r&#225;pido restabelecimento do fluxo sangu&#237;neo, aumentando a &#225;rea de mioc&#225;rdio vi&#225;vel e levando &#224; melhora da fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda. Al&#233;m disso, est&#225; relacionada &#224; redu&#231;&#227;o de complica&#231;&#245;es vasculares pela menor necessidade de pun&#231;&#245;es e &#224; diminui&#231;&#227;o do tempo de interna&#231;&#227;o hospitalar, promovendo aumento de custo-efetividade.</p>
        <p>Por outro lado, as desvantagens da revasculariza&#231;&#227;o completa incluem tempo de procedimento prolongado, com maior exposi&#231;&#227;o &#224; radia&#231;&#227;o e uso de maior volume de contraste, potencializando o risco de nefropatia por contraste. H&#225; ainda maior risco de trombose aguda ou subaguda de <italic>stent</italic> devido ao cen&#225;rio protromb&#243;tico e pr&#243;-inflamat&#243;rio do IAM.<xref ref-type="bibr" rid="B7">7</xref>
				</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>A abordagem multiarterial no mesmo procedimento pode ser utilizada em pacientes selecionados com seguran&#231;a, desde que respeitadas as situa&#231;&#245;es descritas no texto apresentado. Uma abordagem do tratamento multiarterial de todas as les&#245;es severas de forma escalonada durante a interna&#231;&#227;o &#237;ndice parece encontrar embasamento nos ECRs e em uma grande metan&#225;lise recentemente publicados, e seria a alternativa a ser recomendada na maioria dos casos considerando as evid&#234;ncias atuais. No entanto, enquanto n&#227;o houver uma recomenda&#231;&#227;o definitiva, o adequado julgamento cl&#237;nico, do intervencionista em conjunto com o cardiologista cl&#237;nico, permanece como a estrat&#233;gia padr&#227;o a ser tomada.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
