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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">pzHKxPmmGfsDMgdFgrFRsXP</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2023000100207</article-id>
      <article-id pub-id-type="other">00207</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220885</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Estrat&#233;gia Farmacoinvasiva no Infarto do Mioc&#225;rdio com Supradesnivelamento do Segmento ST: Particularidades no Idoso</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1051-9434</contrib-id>
          <name>
            <surname>Cesena</surname>
            <given-names>Fernando</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Cenocor</institution>
        <addr-line>
          <named-content content-type="city">Guarulhos</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Cenocor, Guarulhos, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Fernando Cesena &#8226; Rua Dr. Ramos de Azevedo, 159, sala 1510. CEP 07012-020, Guarulhos, SP &#8211; Brasil E-mail: <email>cesenaf@gmail.com</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>13</day>
        <month>02</month>
        <year>2023</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>01</month>
        <year>2023</year>
      </pub-date>
      <volume>120</volume>
      <issue>1</issue>
      <elocation-id>e20220885</elocation-id>
      <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>
      <kwd-group xml:lang="pt">
        <kwd>Idoso</kwd>
        <kwd>Infarto do Mioc&#225;rdio com Supradesnivelamento do Segmento ST</kwd>
        <kwd>Interven&#231;&#227;o Coron&#225;ria Percut&#226;nea</kwd>
        <kwd>Terapia Trombol&#237;tica/m&#233;todos</kwd>
        <kwd>Revasculariza&#231;&#227;o do Mioc&#225;rdio</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="10"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>O manejo do infarto do mioc&#225;rdio (IM) em idosos &#233; diferente do tratamento de indiv&#237;duos mais jovens. Nos idosos, a apresenta&#231;&#227;o do IM &#233; frequentemente at&#237;pica, mais complexa e tem um pior progn&#243;stico. N&#227;o s&#243; a gravidade da doen&#231;a e a preval&#234;ncia de comorbidades tendem a ser maiores nos idosos, como tamb&#233;m s&#227;o mais frequentes os eventos adversos dos tratamentos, principalmente os sangramentos facilitados por diferentes medica&#231;&#245;es antitromb&#243;ticas. Al&#233;m disso, a diminui&#231;&#227;o da fun&#231;&#227;o renal e a maior suscetibilidade a intera&#231;&#245;es medicamentosas devido ao uso concomitante de m&#250;ltiplos medicamentos potencializam a chance de desfechos ruins.</p>
    <p>No IM com supradesnivelamento do segmento ST (IAMCST), a fibrin&#243;lise seguida pela interven&#231;&#227;o coron&#225;ria percut&#226;nea (ICP) precoce para otimizar a reperfus&#227;o coron&#225;ria, a chamada estrat&#233;gia farmacoinvasiva, &#233; uma terapia recomendada por diretrizes quando a ICP n&#227;o est&#225; prontamente dispon&#237;vel.<sup><xref rid="B1" ref-type="bibr">1</xref> - <xref rid="B4" ref-type="bibr">4</xref> </sup></p>
    <p>Os Arquivos Brasileiros de Cardiologia publicaram um artigo comparando indiv&#237;duos &lt;65 anos versus 65-75 anos submetidos &#224; fibrin&#243;lise seguida de coronariografia invasiva em at&#233; 24 horas ap&#243;s IAMCSST no Brasil.<sup><xref rid="B5" ref-type="bibr">5</xref></sup> Depois de excluir pacientes que morreram, foram readmitidos no hospital, encaminhados para cirurgia de revasculariza&#231;&#227;o do mioc&#225;rdio ou tiveram insufici&#234;ncia renal, os autores avaliaram 223 participantes com resson&#226;ncia magn&#233;tica card&#237;aca (RM, 30 dias ap&#243;s o IM) e um conjunto abrangente de marcadores inflamat&#243;rios (nos dias 1 e 30 ap&#243;s o IM). Os autores observaram pequenas diferen&#231;as nos par&#226;metros inflamat&#243;rios entre os grupos que n&#227;o pareceram afetar os resultados da RM. Em compara&#231;&#227;o com o grupo mais jovem, os participantes mais idosos tiveram uma massa infartada semelhante e fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo levemente maior um m&#234;s ap&#243;s o IM. O estudo n&#227;o teve o objetivo de avaliar desfechos cl&#237;nicos duros, mas os resultados alinham-se ao conceito atual de que a terapia farmacoinvasiva deve ser realizada quando esteja apropriadamente indicada, independentemente da idade, pelo menos at&#233; os 75 anos.</p>
    <p>A pergunta mais relevante &#233;: e os indiv&#237;duos com mais de 75 anos? A esse respeito, algumas observa&#231;&#245;es podem ser feitas. Primeiro, as preocupa&#231;&#245;es sobre o risco de hemorragia que ameace a vida ap&#243;s a fibrin&#243;lise em idosos s&#227;o justific&#225;veis. A idade avan&#231;ada &#233; um preditor claro de sangramento importante ap&#243;s a fibrin&#243;lise. No estudo STREAM, uma taxa excessiva de hemorragia intracraniana (HIC) em participantes &#8805;75 anos levou a uma altera&#231;&#227;o do protocolo recomendando uma redu&#231;&#227;o de 50% na dose de tenecteplase nessa faixa et&#225;ria.<sup><xref rid="B1" ref-type="bibr">1</xref></sup> Uma extensa an&#225;lise de pacientes tratados com dose total de tenecteplase ou alteplase mostrou que o risco de sangramento maior ou HIC come&#231;a a aumentar a partir dos 60 anos.<sup><xref rid="B6" ref-type="bibr">6</xref></sup></p>
    <p>Em segundo lugar, &#233; amplamente aceito que os benef&#237;cios da reperfus&#227;o coronariana com tromb&#243;lise superam o risco de sangramento mesmo naqueles indiv&#237;duos &gt;75 anos. De fato, a idade avan&#231;ada n&#227;o &#233; nem mesmo uma contra-indica&#231;&#227;o relativa para fibrin&#243;lise em IAMCST.<sup><xref rid="B3" ref-type="bibr">3</xref> , <xref rid="B4" ref-type="bibr">4</xref> </sup> Na fase p&#243;s-altera&#231;&#227;o do protocolo do estudo STREAM, n&#227;o houve HIC com meia dose de tenecteplase e a efic&#225;cia da estrat&#233;gia farmacoinvasiva foi mantida em 93 idosos participantes.<sup><xref rid="B7" ref-type="bibr">7</xref></sup></p>
    <p>Em terceiro lugar, os m&#233;dicos devem prestar aten&#231;&#227;o &#224;s particularidades do tratamento farmacoinvasivo em pacientes idosos com IAMCST. N&#227;o s&#243; a dose de tenecteplase deve ser cortada pela metade em indiv&#237;duos &#8805;75 anos, mas a dose de ataque de 300 mg de clopidogrel e o bolus intravenoso inicial de 30 mg de enoxaparina tamb&#233;m devem ser omitidos. Uma redu&#231;&#227;o de 25% na dose de enoxaparina tamb&#233;m &#233; recomendada, pelo menos na fase inicial do tratamento. Al&#233;m disso, na presen&#231;a de disfun&#231;&#227;o renal, deve-se ajustar a dose de enoxaparina ou usar heparina n&#227;o fracionada.<sup><xref rid="B3" ref-type="bibr">3</xref> , <xref rid="B4" ref-type="bibr">4</xref> </sup> Erros de dosagem de antitromb&#243;ticos em idosos com IM podem ser comuns e imp&#245;em um risco mais alto de sangramento maior.<sup><xref rid="B8" ref-type="bibr">8</xref></sup></p>
    <p>Em quarto lugar, o regime antitromb&#243;tico ideal em indiv&#237;duos idosos no contexto de uma estrat&#233;gia farmacoinvasiva em IAMCST &#233; uma quest&#227;o em evolu&#231;&#227;o, e as recomenda&#231;&#245;es podem mudar &#224; medida que novas evid&#234;ncias surgirem. Por exemplo, o estudo STREAM-2 em andamento avalia a efic&#225;cia e a seguran&#231;a de meia dose de tenecteplase e terapia antiplaquet&#225;ria, incluindo uma dose de ataque de 300 mg de clopidogrel, em compara&#231;&#227;o com a ICP prim&#225;ria padr&#227;o, em pacientes com IAMCST com idade &#8805;60 anos.<sup><xref rid="B6" ref-type="bibr">6</xref></sup></p>
    <p>A discuss&#227;o sobre a seguran&#231;a da estrat&#233;gia farmacoinvasiva deve ser inserida no contexto mais amplo da qualidade da assist&#234;ncia ao IAMCSST. No Brasil, h&#225; espa&#231;o para melhorias em v&#225;rios aspectos do tratamento do IAMCSST, incluindo as taxas de terapia de reperfus&#227;o.<sup><xref rid="B9" ref-type="bibr">9</xref></sup> No Registro Brasileiro de S&#237;ndromes Coron&#225;rias Agudas (ACCEPT, pacientes inclu&#237;dos de 2010 a 2014), quase 20% dos participantes n&#227;o receberam terapia de reperfus&#227;o para IAMCSST, e essa taxa sobe para ~35% nas Regi&#245;es Centro-Oeste e Norte.<sup><xref rid="B10" ref-type="bibr">10</xref></sup> A chegada tardia ao pronto-socorro e as contraindica&#231;&#245;es para fibrin&#243;lise podem ser respons&#225;veis por v&#225;rios casos. No entanto, alguns indiv&#237;duos mais idosos podem n&#227;o receber medicamentos fibrinol&#237;ticos devido a preocupa&#231;&#245;es com o risco de sangramento, o que n&#227;o &#233; suportado pela literatura. Em conclus&#227;o, os indiv&#237;duos mais idosos constituem um grupo especial de pacientes com IAMCST. Estudos abordando as particularidades do tratamento nessa popula&#231;&#227;o s&#227;o bem-vindos e necess&#225;rios para fornecer evid&#234;ncias adequadas para otimizar o atendimento m&#233;dico.</p>
  </body>
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          <article-title>Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes</article-title>
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    <fn-group>
      <fn fn-type="other">
        <p>
          <italic>Minieditorial referente ao artigo: Estrat&#233;gia Farmacoinvasiva em Idosos at&#233; 75 Anos ou N&#227;o Idosos: An&#225;lise de Par&#226;metros Bioqu&#237;micos e de Resson&#226;ncia Nuclear Magn&#233;tica Card&#237;aca</italic>
        </p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Pharmacoinvasive Strategy in ST-elevation Myocardial Infarction: Particularities in the Elderly</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1051-9434</contrib-id>
          <name>
            <surname>Cesena</surname>
            <given-names>Fernando</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Cenocor, Guarulhos, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address:Fernando Cesena &#8226; Rua Dr. Ramos de Azevedo, 159, sala 1510. Postal Code 07012-020, Guarulhos, SP &#8211; Brazil E-mail: cesenaf@gmail.com</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Aged</kwd>
        <kwd>ST Elevation Myocardial Infarction</kwd>
        <kwd>Percutaneous Coronary Intervention</kwd>
        <kwd>Thrombolytic Therapy/methods</kwd>
        <kwd>Myocardial Revascularization</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Managing myocardial infarction (MI) in older people differs from treating younger individuals. In the elderly, MI presentation is often atypical, more complex, and has a worse prognosis. Not only do the disease severity and the prevalence of comorbidities tend to be higher in the elderly, but adverse events from treatments are also more frequent, particularly bleeding facilitated by different antithrombotic medications. Moreover, decreased renal function and the higher susceptibility to drug interactions due to the concomitant use of multiple medications potentiate the chance of bad outcomes.</p>
      <p>In ST-elevation MI (STEMI), fibrinolysis followed by the early percutaneous coronary intervention (PCI) to optimize coronary reperfusion, the so-called pharmacoinvasive strategy, is a guideline-recommended therapy when timely PCI is not available.<sup><xref rid="B1" ref-type="bibr">1</xref> - <xref rid="B4" ref-type="bibr">4</xref> </sup></p>
      <p>The <italic>Arquivos Brasileiros de Cardiologia</italic> published an article comparing individuals &lt;65 years versus 65-75 years who underwent fibrinolysis followed by invasive coronary angiography within 24 hours after STEMI in Brazil.<sup><xref rid="B5" ref-type="bibr">5</xref></sup>After excluding patients who died, were readmitted to the hospital, referred for coronary artery bypass surgery, or had renal failure, the authors evaluated 223 participants with cardiac magnetic resonance (MR, 30 days after the MI) and a comprehensive set of inflammatory markers (at days 1 and 30 after the MI). The authors observed minor differences in inflammatory parameters between the groups that did not seem to impact MR outcomes. Compared to the younger group, older participants had a similar infarcted mass and mildly higher left ventricular ejection fraction one month after the MI. The study did not have the objective of evaluating hard clinical endpoints, but the results align with the current concept that pharmacoinvasive therapy should be performed when properly indicated, regardless of age, at least until 75 years.</p>
      <p>The more relevant question is: what about individuals older than 75 years? In this regard, some remarks can be made. First, concerns about the risk of life-threatening hemorrhage after fibrinolysis in older people are justifiable. Advanced age is a clear predictor of major bleeding after fibrinolysis. In the STREAM trial, an excess rate of intracranial hemorrhage (ICH) in participants &#8805;75 years prompted a protocol amendment recommending a 50% decrease in the tenecteplase dose in this age group.<sup><xref rid="B1" ref-type="bibr">1</xref></sup>An extensive analysis of patients treated with full tenecteplase dose or alteplase has shown that the risk of major bleeding or ICH increases from ~60 years.<sup><xref rid="B6" ref-type="bibr">6</xref></sup></p>
      <p>Second, it is widely accepted that the benefits of coronary reperfusion with thrombolysis surpass the bleeding risk even in those individuals &gt;75 years. Indeed, older age is not even a relative contraindication for fibrinolysis in STEMI.<sup><xref rid="B3" ref-type="bibr">3</xref> , <xref rid="B4" ref-type="bibr">4</xref> </sup>In the post-protocol amendment phase of the STREAM trial, there was no ICH with half-dose tenecteplase, and the efficacy of the pharmacoinvasive strategy was maintained among 93 elderly participants.<sup><xref rid="B7" ref-type="bibr">7</xref></sup></p>
      <p>Third, clinicians must pay attention to particularities of the pharmacoinvasive treatment in older STEMI patients. Not only should the tenecteplase dose be cut in half in individuals &#8805;75 years, but the loading dose of 300 mg clopidogrel and the initial 30 mg intravenous bolus of enoxaparin should also be omitted. A 25% reduction in the enoxaparin dose is also recommended, at least in the initial phase of treatment. In addition, in the presence of renal dysfunction, the enoxaparin dose should be adjusted, or unfractionated heparin should be used.<sup><xref rid="B3" ref-type="bibr">3</xref> , <xref rid="B4" ref-type="bibr">4</xref> </sup>Dosing errors of antithrombotics in older people with MI may be common and impose a higher risk of major bleeding.<sup><xref rid="B8" ref-type="bibr">8</xref></sup></p>
      <p>Fourth, the optimal antithrombotic regimen in older individuals in the context of a pharmacoinvasive strategy in STEMI is an evolving issue, and recommendations may change as new evidence emerges. For instance, the ongoing STREAM-2 trial evaluates the efficacy and safety of half-dose tenecteplase and antiplatelet therapy, including a loading dose of 300 mg clopidogrel, compared to standard primary PCI, in STEMI patients aged &#8805;60 years.<sup><xref rid="B6" ref-type="bibr">6</xref></sup></p>
      <p>The discussion on the safety of the pharmacoinvasive strategy should be put into the broader context of STEMI care quality. In Brazil, there is room for improvement in several aspects of STEMI treatment, including the rates of reperfusion therapy.<sup><xref rid="B9" ref-type="bibr">9</xref></sup>In the Brazilian Registry of Acute Coronary Syndromes (ACCEPT, patients included from 2010 to 2014), nearly 20% of the participants did not receive reperfusion therapy for STEMI, and this rate rises to ~35% in the Midwest and Northern Regions.<sup><xref rid="B10" ref-type="bibr">10</xref></sup>Late arrival at the emergency room and contraindications for fibrinolysis may account for several cases. However, some older individuals may not be prescribed fibrinolytic drugs due to concerns about the bleeding risk, which is not supported by the literature. In conclusion, older individuals constitute a special group of STEMI patients. Studies addressing the particularities of treatment in this population are welcome and necessary to provide adequate evidence to optimize medical care.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <italic>Short Editorial related to the article: Pharmacoinvasive Strategy in Elderly Up to 75 Years or Non-Elderly: Analysis of Biochemical and Cardiac Magnetic Resonance Imaging Parameters</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
