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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">mtkqNksdB7c5B3zvg7VZQQp</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2024000700209</article-id>
      <article-id pub-id-type="other">00209</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20240409</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Avan&#231;ando no Uso de Anticoagulantes Orais Diretos no Manejo do Trombo Ventricular Esquerdo</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-0918-6759</contrib-id>
          <name>
            <surname>Carvalho</surname>
            <given-names>Pedro E. P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Minneapolis Heart Institute Foundation</institution>
          <addr-line>
            <named-content content-type="city">Minneapolis</named-content>
          </addr-line>
          <country country="US">EUA</country>
          <institution content-type="original">Center for Coronary Artery Disease - Minneapolis Heart Institute Foundation, Minneapolis - EUA</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Pedro E. P. Carvalho</bold> &#8226; Center for Coronary Artery Disease, Minneapolis Heart Institute Foundation - 920E 28th St #100, Minneapolis, MN 55407 E-mail: <email>pedroemanuel.carvalho@gmail.com</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>22</day>
        <month>11</month>
        <year>2024</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2024</year>
      </pub-date>
      <volume>121</volume>
      <issue>7</issue>
      <elocation-id>e20240409</elocation-id>
      <history>
        <date date-type="received">
          <day>10</day>
          <month>06</month>
          <year>2024</year>
        </date>
        <date date-type="rev-recd">
          <day>26</day>
          <month>06</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>26</day>
          <month>06</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Inibidores do Fator Xa</kwd>
        <kwd>Tromboembolia Venosa</kwd>
        <kwd>Infarto do Mioc&#225;rdio</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="15"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>Os anticoagulantes orais diretos (DOACs) s&#227;o preferidos aos antagonistas da vitamina K (AVKs) em v&#225;rios cen&#225;rios cl&#237;nicos, como na preven&#231;&#227;o de eventos tromboemb&#243;licos em pacientes com fibrila&#231;&#227;o atrial e no tratamento de tromboembolismo venoso.<sup><xref ref-type="bibr" rid="B1">1</xref>&#8211;<xref ref-type="bibr" rid="B4">4</xref></sup> Em contraste, os DOACs s&#227;o contraindicados em pacientes com v&#225;lvulas card&#237;acas mec&#226;nicas, FA valvar devido a estenose mitral e s&#237;ndrome antifosfol&#237;pide.<sup><xref ref-type="bibr" rid="B5">5</xref>&#8211;<xref ref-type="bibr" rid="B7">7</xref></sup> Em pacientes com trombo ventricular esquerdo (TVE), entretanto, a efic&#225;cia e seguran&#231;a dos DOACs permanecem incertas.</p>
    <p>TVE &#233; uma complica&#231;&#227;o comum ap&#243;s um infarto agudo do mioc&#225;rdio (IAM). A incid&#234;ncia de TVE p&#243;s-IAM agudo diminuiu devido ao aumento da interven&#231;&#227;o coron&#225;ria percut&#226;nea prim&#225;ria (ICP) e terapias antitromb&#243;ticas avan&#231;adas. Na era da ICP prim&#225;ria, a incid&#234;ncia de TVE &#233; de at&#233; 6,3% em pacientes com IAMCSST, aumentando para 19,2% naqueles com IAMCSST anterior e fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda reduzida.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Dados do registro SWEDEHEART indicaram uma incid&#234;ncia de at&#233; 38%, sugerindo subestima&#231;&#227;o e necessidade de acompanhamento para avaliar a forma&#231;&#227;o de TVE nesses pacientes.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Al&#233;m disso, a escolha da modalidade de imagem impacta significativamente a detec&#231;&#227;o de TVE, com a resson&#226;ncia magn&#233;tica card&#237;aca tendo maior sensibilidade em compara&#231;&#227;o com a ecocardiografia.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Portanto, existe uma necessidade n&#227;o atendida de preven&#231;&#227;o, detec&#231;&#227;o e tratamento de TVE.</p>
    <p>Quando presente, o TVE est&#225; associado a um alto risco de acidente vascular cerebral e embolia sist&#234;mica, mesmo ap&#243;s tratamento anticoagulante. O manejo &#233; desafiador devido &#224; falta de dados randomizados com poder suficiente para abordar esta quest&#227;o cl&#237;nica. Atualmente, n&#227;o h&#225; recomenda&#231;&#227;o de rotina para profilaxia de TVE p&#243;s-IAM agudo. Um pequeno ECR demonstrou que doses baixas de rivaroxabana combinada com terapia antiplaquet&#225;ria dupla (TAPD) versus TAPD isolada reduziram a incid&#234;ncia de TVE em 30 dias sem aumentar o sangramento maior.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> O ensaio APERITIF em andamento (NCT05077683) pretende randomizar mais de 500 participantes para analisar tamb&#233;m se a adi&#231;&#227;o de DOAC &#224; TAPD &#233; segura e eficaz na preven&#231;&#227;o de TVE.</p>
    <p>Os dados tradicionalmente apoiam o uso de AVKs para tratar TVE estabelecida, apesar do aumento do uso off-label de DOACs. Recentemente, uma declara&#231;&#227;o cient&#237;fica da AHA considerou os DOACs uma alternativa razo&#225;vel aos AVK.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Nesta edi&#231;&#227;o dos Arquivos Brasileiros de Cardiologia &#233; apresentada uma metan&#225;lise comparando AVKs com DOACs em pacientes com TVE.<sup><xref ref-type="bibr" rid="B13">13</xref>&#8211;<xref ref-type="bibr" rid="B15">15</xref></sup> Esta an&#225;lise incluiu quatro pequenos ensaios cl&#237;nicos randomizados (ECR) e 29 estudos observacionais, abrangendo 4.450 pacientes. Os resultados indicam taxas de eventos tromboemb&#243;licos semelhantes entre AVKs e DOACs, com a rivaroxabana mostrando uma redu&#231;&#227;o nos eventos tromboemb&#243;licos na an&#225;lise de subgrupo em compara&#231;&#227;o com AVKs.</p>
    <p>Esta metan&#225;lise oportuna apoia o uso de DOACs em pacientes com TVE, incluindo um estudo randomizado adicional e v&#225;rios estudos observacionais n&#227;o considerados na declara&#231;&#227;o da AHA. Os autores conclu&#237;ram que n&#227;o houve diferen&#231;a significativa nos resultados hemorr&#225;gicos entre DOACs e AVKs, mas foi observado um efeito protetor dos DOACs em v&#225;rios resultados hemorr&#225;gicos, sugerindo que a falta de signific&#226;ncia estat&#237;stica n&#227;o deveria implicar uma falta de diferen&#231;a cl&#237;nica.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Especialmente considerando que os AVKs est&#227;o associados a intera&#231;&#245;es medicamentosas e alimentares, dose-resposta imprevis&#237;vel e uma faixa terap&#234;utica estreita, necessitando de monitoramento rigoroso do tempo de protrombina.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
    <p>Dada a natureza observacional da maioria dos estudos inclu&#237;dos, existem preocupa&#231;&#245;es sobre vi&#233;s de sele&#231;&#227;o e vari&#225;veis de confus&#227;o, limitando a interpreta&#231;&#227;o dos resultados. Devido ao desafio de alocar grandes coortes de pacientes com TVE em ECRs, &#233; improv&#225;vel obter dados randomizados em um futuro pr&#243;ximo. Este estudo, no entanto, orienta a extens&#227;o do uso de DOAC nesta popula&#231;&#227;o de pacientes, enfatizando a necessidade de evid&#234;ncias adicionais para melhorar os resultados cl&#237;nicos em pacientes com TVE.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Anticoagulantes Orais Diretos versus Antagonistas da Vitamina K para Trombo Ventricular Esquerdo: Uma Metan&#225;lise com An&#225;lise Sequencial de Ensaios</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20240409i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Advancing the Use of Direct Oral Anticoagulants in Left Ventricular Thrombus Management</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0002-0918-6759</contrib-id>
          <name>
            <surname>Carvalho</surname>
            <given-names>Pedro E. P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Minneapolis</named-content>
          </addr-line>
          <country country="US">USA</country>
          <institution content-type="original">Center for Coronary Artery Disease - Minneapolis Heart Institute Foundation, Minneapolis &#8211; USA</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Pedro E. P. Carvalho</bold> &#8226; Center for Coronary Artery Disease, Minneapolis Heart Institute Foundation - 920E 28th St #100, Minneapolis, MN 55407 E-mail: <email>pedroemanuel.carvalho@gmail.com</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Factor Xa Inhibitors</kwd>
        <kwd>Venous Thromboembolism</kwd>
        <kwd>Myocardial Infarction</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Direct oral anticoagulants (DOACs) are preferred over Vitamin K Antagonists (VKAs) in numerous clinical scenarios, such as preventing thromboembolic events in patients with atrial fibrillation and treating venous thromboembolism.<sup><xref ref-type="bibr" rid="B1">1</xref>&#8211;<xref ref-type="bibr" rid="B4">4</xref></sup> In contrast, DOACs are contraindicated in patients with mechanical heart valves, valvular AF due to mitral stenosis, and antiphospholipid syndrome.<sup><xref ref-type="bibr" rid="B5">5</xref>&#8211;<xref ref-type="bibr" rid="B7">7</xref></sup> In patients with left ventricular thrombus (LVT), however, the efficacy and safety of DOACs remain uncertain.</p>
      <p>LVT is a common complication following an acute myocardial infarction (MI). The incidence of LVT post-acute MI has declined due to increased primary percutaneous coronary intervention (PCI) and advanced antithrombotic therapies. In the primary PCI era, LVT incidence is up to 6.3% in STEMI patients, rising to 19.2% in those with anterior STEMI and reduced left ventricular ejection fraction.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Data from the SWEDEHEART registry indicated an incidence as high as 38%, suggesting underestimation and the need for follow-up to assess LVT formation in these patients.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> In addition, the choice of imaging modality significantly impacts LVT detection, with cardiac magnetic resonance having higher sensitivity compared with echocardiography.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Therefore, there is an unmet need for LVT prevention, detection, and treatment.</p>
      <p>When present, LVT is associated with a high risk of stroke and systemic embolism, even post anticoagulant treatment. Management is challenging due to a lack of sufficiently powered randomized data addressing this clinical issue. Currently, there is no routine recommendation for LVT prophylaxis post-acute MI. A small RCT demonstrated that low-dose rivaroxaban combined with dual antiplatelet therapy (DAPT) versus DAPT alone reduced LVT incidence within 30 days without increasing major bleeding.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> The ongoing APERITIF trial (NCT05077683) aims to enroll over 500 participants to also analyze whether the addition of DOAC to DAPT is safe and effective in preventing LVT.</p>
      <p>Data traditionally support the use of VKAs to treat established LVT despite the increasing off-label use of DOACs. Recently, an AHA scientific statement deemed DOACs a reasonable VKA alternative.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> In this issue of the <italic>Arquivos Brasileiros de Cardiologia</italic>, a meta-analysis comparing VKAs with DOACs in LVT patients is presented.<sup><xref ref-type="bibr" rid="B13">13</xref>&#8211;<xref ref-type="bibr" rid="B15">15</xref></sup> This analysis included four small randomized controlled trials (RCTs) and 29 observational studies, encompassing 4,450 patients. The findings indicate similar thromboembolic event rates between VKAs and DOACs, with rivaroxaban showing a reduction in thromboembolic events compared with VKAs in a subgroup analysis.</p>
      <p>This timely meta-analysis supports the use of DOACs in patients with LVT by including an additional randomized study and numerous observational studies not considered in the AHA statement. The authors concluded there was no significant difference in bleeding outcomes between DOACs and VKAs, but a protective effect of DOACs in several bleeding outcomes was observed, suggesting that the lack of statistical significance should not imply a lack of clinical difference.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Especially considering that VKAs are associated with drug and food interactions, unpredictable dose-response, and a narrow therapeutic range, necessitating close monitoring of prothrombin time.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
      <p>Given the observational nature of most included studies, there are concerns about selection bias and confounding, limiting results interpretation. Due to the challenge of enrolling large LVT patient cohorts in RCTs, obtaining randomized data is unlikely soon. This study, however, guides extending DOAC use in this patient population, emphasizing the need for additional evidence to improve clinical outcomes in patients with LVT.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short Editorial related to the article: Direct Oral Anticoagulants versus Vitamin K Antagonists for Left Ventricular Thrombus: A Meta-Analysis with Trial Sequential Analysis</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
