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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="editorial" dtd-version="1.1" specific-use="sps-1.9" xml:lang="pt">
  <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">GCgRprSYWBzQyKcHhbpxtXw</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022000900370</article-id>
      <article-id pub-id-type="publisher-id">abc.20220504</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220504</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Terapia de Anticoagula&#231;&#227;o com Varfarina: Uma Realidade da Sa&#250;de P&#250;blica Brasileira que Carece de Estrutura para Melhor Controle</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4440-8078</contrib-id>
          <name>
            <surname>Martinelli</surname>
            <given-names>Martino</given-names>
            <suffix>Filho</suffix>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Martino Martinelli Filho &#8226; Av. Dr. En&#233;as de Carvalho Aguiar, 44. CEP 05403-000, Cerqueira Cesar, S&#227;o Paulo, SP &#8211; Brasil Email: <email>martinomartinelli@uol.com.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>05</day>
        <month>09</month>
        <year>2022</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>09</month>
        <year>2022</year>
      </pub-date>
      <volume>119</volume>
      <issue>3</issue>
      <fpage>370</fpage>
      <lpage>371</lpage>
      <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>Fibrila&#231;&#227;o Atrial</kwd>
        <kwd>Anticoagulantes/uso terap&#234;utico</kwd>
        <kwd>Acidente Vascular Cerebral</kwd>
        <kwd>Hemorragia</kwd>
        <kwd>Tromboembolia</kwd>
        <kwd>Varfarina/efeitos adversos</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="11"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>O aumento da longevidade, nas &#250;ltimas d&#233;cadas, levou ao incremento progressivo da preval&#234;ncia da fibrila&#231;&#227;o atrial (FA), em todo o mundo.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup></p>
    <p>Com isso, a terapia de anticoagula&#231;&#227;o passou a ser cada vez mais indicada na preven&#231;&#227;o de eventos tromboemb&#243;licos. A necessidade de uso cont&#237;nuo dirigiu a prefer&#234;ncia para anticoagulantes orais, historicamente representados por f&#225;rmacos antivitamina K (AVK) e, mais recentemente, por novos anticoagulantes (anti fator X). Dentre esses, a varfarina, um AVK, &#233; o de maior destaque pelo baixo custo.</p>
    <p>Entretanto, pelo fato da varfarina ter estreita janela terap&#234;utica, seu uso exige um manuseio visando o equil&#237;brio entre evitar subdoses que s&#227;o incapazes de prevenir eventos tromboemb&#243;licos e a superdosagem que pode causar eventos hemorr&#225;gicos. Esse manuseio da varfarina &#233; dificultado pela enorme variabilidade interindividual de resposta medicamentosa, assim como pelo grande n&#250;mero de intera&#231;&#245;es com outros f&#225;rmacos e alimentos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>A varfarina est&#225; entre os dez medicamentos mais relacionados &#224; ocorr&#234;ncia de erros de dispensa&#231;&#227;o. Nos Estados Unidos e na Austr&#225;lia, os anticoagulantes orais est&#227;o entre as cinco classes mais relacionadas a eventos graves secund&#225;rios ao uso de medicamentos. <sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
    <p>No Brasil, o Instituto de Pr&#225;ticas Seguras no Uso de Medicamentos (IPSM) inclui a varfarina como droga de alta vigil&#226;ncia, isto &#233;, de uso potencialmente perigoso.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> O ajuste da dose ideal de varfarina &#233; monitorado pela Raz&#227;o Normalizada Internacional (RNI) e a efici&#234;ncia medicamentosa &#233; estimada pelo tempo na faixa terap&#234;utica (TTR), per&#237;odo de RNI com valores entre 2,0 e 3,0. Existem poucos dados sobre TTR em pacientes com FA na pr&#225;tica comunit&#225;ria, mas &#233; preciso difundir essa ferramenta cada vez mais.</p>
    <p>A taxa de uso da varfarina na rede de sa&#250;de p&#250;blica do Brasil &#233; elevada e o custo-efetividade &#233; controverso.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> Existem barreiras pr&#225;ticas s&#233;rias para seu uso em nosso meio: baixa ader&#234;ncia causada por limitados recursos financeiros e/ou baixo n&#237;vel sociocultural, assim como complexidade do manuseio do f&#225;rmaco pelos profissionais da sa&#250;de. Nesse sentido, h&#225; evid&#234;ncias de que os m&#233;dicos brasileiros est&#227;o pouco familiarizados com a administra&#231;&#227;o apropriada da varfarina aos pacientes.</p>
    <p>Colet et al.,<sup><xref ref-type="bibr" rid="B7">7</xref></sup> reportaram o baixo n&#237;vel de conhecimento de profissionais da sa&#250;de p&#250;blica de um hospital p&#250;blico do estado do Rio Grande do Sul sobre o uso da varfarina. Os autores verificaram que n&#227;o existe estrat&#233;gia institucional para tratar do tema e sugerem que os servi&#231;os de sa&#250;de incluam programas de educa&#231;&#227;o, pelo menos aos mais vulner&#225;veis a eventos adversos, para aumentar a seguran&#231;a dos pacientes.</p>
    <p>Pokorney et al.,<sup><xref ref-type="bibr" rid="B8">8</xref></sup> reportaram achados espec&#237;ficos da anticoagula&#231;&#227;o com warfarina de 5.210 pacientes do registro americano de FA (ORBIT-AF). Ao longo de 18 meses, o TTR m&#233;dio foi de 65% &#177; 20% com mediana de 68%. Os pacientes com TTR &#8804; 53% eram mais frequentemente do sexo feminino e tinham menos educa&#231;&#227;o universit&#225;ria do que pacientes com TTR mais elevado. Pacientes com diabetes mellitus, insufici&#234;ncia renal ou cardiomiopatia tamb&#233;m foram menos propensos a apresentar TTR elevado. Entretanto, o achado impactante deste estudo foi a associa&#231;&#227;o de valor de TTR significativamente superior (p &lt;0,0001) entre pacientes assistidos em cl&#237;nica de anticoagula&#231;&#227;o (69%) versus assist&#234;ncia ambulatorial geral (66%)</p>
    <p>Nesta edi&#231;&#227;o dos Arquivos Brasileiros de Cardiologia, Bazan et al.,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> reportam, em estudo realizado em hospital terci&#225;rio do estado de S&#227;o Paulo, valor m&#233;dio de TTR de 52,2% dentre 203 pacientes com FA n&#227;o valvar. Os autores consideraram esse achado aceit&#225;vel, associando-o a fatores culturais e socioecon&#244;micos. O manuscrito cont&#233;m informa&#231;&#245;es valiosas, mas escancara as limita&#231;&#245;es do nosso sistema p&#250;blico na preven&#231;&#227;o de fen&#244;menos tromboemb&#243;licos dessa popula&#231;&#227;o.</p>
    <p>Valores de TTR inferiores a 60% s&#227;o indicativos de baixa qualidade de anticoagula&#231;&#227;o. No estudo de Bazan et al.,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> 63,5% dos pacientes apresentaram valores de TTR inferiores a 60%, associando essa popula&#231;&#227;o a maiores taxas de mortalidade global, sangramento maior, acidente vascular cerebral e tromboembolismo sist&#234;mico.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Os valores m&#233;dios estimados para pa&#237;ses da Europa Ocidental e Canad&#225;/Estados Unidos s&#227;o respectivamente 63,2% e 64,1%.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Mesmo para Am&#233;rica Latina, o valor m&#233;dio (55,2%)<sup><xref ref-type="bibr" rid="B11">11</xref></sup> &#233; superior ao reportado por Bazan et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
    <p>Por outro lado, o achado mais relevante desse estudo, associa&#231;&#227;o entre instabilidade de RNI na fase de adapta&#231;&#227;o &#224; anticoagula&#231;&#227;o com maiores taxas de eventos adversos, corroborou a falta de controle do processo global porque correspondeu a valores m&#233;dios de TTR muito baixos (m&#233;dia de 46,83%).</p>
    <p>Ent&#227;o, conclui-se que, para otimizar taxas de sucesso de anticoagula&#231;&#227;o com varfarina em nosso meio, &#233; preciso criar cl&#237;nicas de anticoagula&#231;&#227;o multidisciplinares compostas por m&#233;dico, farmac&#234;utico, enfermeiro, assistente social e psic&#243;logo.</p>
    <p>As cl&#237;nicas de anticoagula&#231;&#227;o devem atuar por meio de protocolos assistenciais de manuseio da varfarina pela equipe multidisciplinar, e de programas educacionais dirigidos aos pacientes.</p>
    <p>Por fim, &#233; importante destacar que as metas para controle do uso de varfarina pelo nosso sistema de sa&#250;de p&#250;blica devem focar as taxas de efici&#234;ncia obtidas pelos melhores centros do mundo, tal qual procedemos com in&#250;meros programas nacionais bem-sucedidos.</p>
  </body>
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    <fn-group>
      <fn fn-type="other">
        <p>
          <italic>Minieditorial referente ao artigo: Qualidade da Anticoagula&#231;&#227;o Oral em Pacientes com Fibrila&#231;&#227;o Atrial em um Hospital Terci&#225;rio no Brasil</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>Anticoagulation Therapy with Warfarin: A Reality of Brazilian Public Health that Lacks Structure for Better Control</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4440-8078</contrib-id>
          <name>
            <surname>Martinelli</surname>
            <given-names>Martino</given-names>
            <suffix>Filho</suffix>
          </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">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Martino Martinelli Filho &#8226; Av. Dr. En&#233;as de Carvalho Aguiar, 44. Postal Code 05403-000, Cerqueira Cesar, S&#227;o Paulo, SP &#8211; Brazil Email: martinomartinelli@uol.com.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Atrial Fibrillation</kwd>
        <kwd>Anticoagulants/therapeutic use</kwd>
        <kwd>Stroke</kwd>
        <kwd>Hemorrhage</kwd>
        <kwd>Thromboembolism</kwd>
        <kwd>Warfarin/adverse effects</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>The increase in longevity in recent decades has led to a progressive increase in the prevalence of atrial fibrillation (AF) worldwide.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>As a result, anticoagulation therapy has become increasingly indicated in preventing thromboembolic events. The need for continuous use drove the preference for oral anticoagulants, historically represented by antivitamin K (VKA) drugs and, more recently, by new anticoagulants (anti-factor X). Among these, a VKA, warfarin, is the most prominent for its low cost.</p>
      <p>However, because warfarin has a narrow therapeutic window, its use requires a balance between avoiding underdoses that cannot prevent thromboembolic events and overdoses that can cause bleeding. This handling of warfarin is hampered by the enormous inter-individual variability of drug response and a large number of interactions with other drugs and foods.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>Warfarin is among the ten drugs most related to dispensing errors. In the United States and Australia, oral anticoagulants are among the five classes most related to serious events secondary to medication use.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>In Brazil, the Institute for Safe Practices in the Use of Medicines (IPSM) includes warfarin as a high surveillance drug and potentially dangerous use.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> The ideal dose of warfarin adjustment is monitored by the International Normalized Ratio (INR), and the drug efficiency is estimated by the time in the therapeutic range (TTR), period of INR with values between 2.0 and 3.0. There are few data on TTR in patients with AF in community practice, but this tool needs to be increasingly disseminated.</p>
      <p>The use rate of warfarin in the public health network in Brazil is high, and the cost-effectiveness is controversial.<sup><xref ref-type="bibr" rid="B6">6</xref></sup> There are serious practical barriers to its use in our country: low adherence caused by limited financial resources and/or low sociocultural status, as well as the complexity of drug handling by health professionals. In this sense, there is evidence that Brazilian physicians are unfamiliar with the proper administration of warfarin to patients.</p>
      <p>Colet et al.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> reported the low knowledge of public health professionals at a public hospital in the Rio Grande do Sul about using warfarin. The authors found no institutional strategy to address the issue and suggest that health services include education programs for those most vulnerable to adverse events to increase patient safety.</p>
      <p>Pokorney et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> reported specific findings of warfarin anticoagulation in 5,210 patients from the American AF Registry (ORBIT-AF). Over 18 months, the mean TTR was 65% &#177; 20%, with a median of 68%. Patients with TTR &#8804; 53% were more often female and had less college education than patients with higher TTR. Patients with diabetes mellitus, renal failure, or cardiomyopathy were also less likely to have an elevated TTR. However, the striking finding of this study was the association of TTR values significantly higher (p &lt; 0.0001) among patients seen in the clinic of anticoagulation (69%) versus general outpatient care (66%)</p>
      <p>In this issue of <italic>Arquivos Brasileiros de Cardiologia</italic> , Bazan et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> report that in a study performed in a tertiary hospital in the state of S&#227;o Paulo, the mean TTR value of 52.2% among 203 patients with non-valvular AF. The authors considered this finding acceptable, associating it with cultural and socioeconomic factors. The manuscript contains valuable information but reveals the limitations of our public system in preventing thromboembolic phenomena in this population.</p>
      <p>TTR values lower than 60% are indicative of poor anticoagulation quality. In the study by Bazan et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> 63.5% of patients had TTR values below 60%, associating this population with higher rates of global mortality, major bleeding, stroke and systemic thromboembolism.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> The average values estimated for Western Europe and Canada/United States countries are 63.2% and 64.1%.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Even for Latin America, the average value (55.2%)11 is higher than that reported by Bazan et al.<sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
      <p>On the other hand, the most relevant finding of this study, the association between INR instability in the anticoagulation adaptation phase with higher rates of adverse events, corroborated the lack of control of the global process because it corresponded to very low mean TTR values (mean of 46 .83%).</p>
      <p>Therefore, it is concluded that to optimize success rates of anticoagulation with warfarin in our country, it is necessary to create multidisciplinary anticoagulation clinics composed of physicians, pharmacists, nurses, social workers and psychologists.</p>
      <p>Anticoagulation clinics should operate through care protocols for handling warfarin by the multidisciplinary team and educational programs aimed at patients.</p>
      <p>Finally, it is important to highlight that the goals for controlling the use of warfarin by our public health system must focus on the efficiency rates obtained by the best centers in the world, as we have done with numerous successful national programs.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>
            <italic>Short Editorial related to the article: Quality of Oral Anticoagulation in Atrial Fibrillation Patients at a Tertiary Hospital in Brazil</italic>
          </p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
