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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">Mnx7MjJqnVFLn4dMTLqbzZz</article-id>
      <article-id specific-use="previous-pid" pub-id-type="publisher-id">S0066-782X2022005016204</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022001100756</article-id>
      <article-id pub-id-type="publisher-id">abc.20210953</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210953</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Avalia&#231;&#227;o do Impacto da Implanta&#231;&#227;o de um Sistema de Ambul&#226;ncia Pr&#233;-Hospitalar sobre Mortalidade por Infarto Agudo do Mioc&#225;rdio em um Pa&#237;s em Desenvolvimento</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Rodrigo Costa Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4278-3771</contrib-id>
          <name>
            <surname>Marcolino</surname>
            <given-names>Milena Soriano</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8297-8704</contrib-id>
          <name>
            <surname>Silva</surname>
            <given-names>Luis Gustavo Silva e</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3124-9322</contrib-id>
          <name>
            <surname>Pereira</surname>
            <given-names>Daniella Nunes</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5586-774X</contrib-id>
          <name>
            <surname>Nascimento</surname>
            <given-names>Bruno Ramos</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1366-1732</contrib-id>
          <name>
            <surname>Jorge</surname>
            <given-names>Alzira de Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2740-0042</contrib-id>
          <name>
            <surname>Ribeiro</surname>
            <given-names>Antonio Luiz P</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label> 1 </label>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Hospital Universit&#225;rio</institution>
        <institution content-type="orgname">Universidade Federal de Minas Gerais</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original"> Faculdade de Medicina e Hospital Universit&#225;rio , Universidade Federal de Minas Gerais , Belo Horizonte , MG &#8211; Brasil </institution>
      </aff>
      <aff id="aff2">
        <label> 2 </label>
        <institution content-type="orgname">Rede de Telessa&#250;de de Minas Gerais</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original"> Rede de Telessa&#250;de de Minas Gerais , Belo Horizonte , MG &#8211; Brasil </institution>
      </aff>
      <author-notes>
        <corresp id="c01">Correspond&#234;ncia: Antonio Luiz P Ribeiro &#8226; Universidade Federal de Minas Gerais - Avenida Professor Alfredo Balena, 110, 1&#186; Andar, Ala Sul, Sala 107. CEP 30130-100, Belo Horizonte, MG &#8211; Brasil E-mail: <email>tom1963br@yahoo.com.br</email> , <email>tom@hc.ufmg.br</email> </corresp>
        <fn fn-type="con">
          <p>Contribui&#231;&#227;o dos autores</p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Vieira RCP, Marcolino MS, Nascimento BR, Ribeiro ALP; Obten&#231;&#227;o de dados e An&#225;lise estat&#237;stica: Vieira RCP, Marcolino MS, Silva LGS; An&#225;lise e interpreta&#231;&#227;o dos dados: Vieira RCP, Marcolino MS, Silva LGS, Ribeiro ALP; Obten&#231;&#227;o de financiamento: Vieira RCP, Marcolino MS, Ribeiro ALP; Reda&#231;&#227;o do manuscrito: Vieira RCP, Marcolino MS, Pereira DN, Jorge AO, Ribeiro ALP; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Vieira RCP, Marcolino MS, Silva LGS, Pereira DN, Nascimento BR, Jorge AO, Ribeiro ALP.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potencial conflito de interesse</p>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>15</day>
        <month>09</month>
        <year>2022</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2022</year>
      </pub-date>
      <volume>119</volume>
      <issue>5</issue>
      <fpage>756</fpage>
      <lpage>763</lpage>
      <history>
        <date date-type="received">
          <day>07</day>
          <month>12</month>
          <year>2021</year>
        </date>
        <date date-type="rev-recd">
          <day>05</day>
          <month>07</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <day>01</day>
          <month>06</month>
          <year>2022</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>Resumo</title>
        <sec>
          <title>Fundamento</title>
          <p>O manejo efetivo de pacientes com infarto agudo do mioc&#225;rdio (IAM) &#233; tempo-dependente.</p>
        </sec>
        <sec>
          <title>Objetivos</title>
          <p>Avaliar os impactos da implanta&#231;&#227;o do atendimento pr&#233;-hospitalar nas taxas de interna&#231;&#227;o e de mortalidade associadas ao IAM.</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p>Estudo retrospectivo e ecol&#243;gico, que avaliou dados do Sistema &#218;nico de Sa&#250;de, de todos os 853 munic&#237;pios de Minas Gerais, de 2008 a 2016. A assimetria excessiva da mortalidade geral e intra-hospitalar por IAM foi suavizada usando o m&#233;todo emp&#237;rico de Bayes. Este estudo avaliou a rela&#231;&#227;o entre o do Servi&#231;o de Atendimento M&#233;dico de Urg&#234;ncia (SAMU) em cada munic&#237;pio e os seguintes 3 desfechos: taxa de mortalidade geral por IAM, taxa de mortalidade intra-hospitalar por IAM e taxa de interna&#231;&#227;o por IAM, utilizando o modelo hier&#225;rquico de Poisson. As taxas foram corrigidas pela estrutura et&#225;ria e destendenciadas pela sazonalidade e influ&#234;ncias temporais. Foi adotado um intervalo de confian&#231;a de 95%.</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p>As taxas de mortalidade por IAM diminu&#237;ram ao longo do estudo, em m&#233;dia 2% por ano, com varia&#231;&#227;o sazonal. A mortalidade intra-hospitalar tamb&#233;m apresentou tend&#234;ncia de queda, de 13,81% em 2008 para 11,43% em 2016. A implanta&#231;&#227;o do SAMU foi associada &#224; diminui&#231;&#227;o da mortalidade por IAM ( <italic>odds ratio</italic> [OR] = 0,967, IC 95% 0,936 a 0,998) e mortalidade intra-hospitalar por IAM (OR = 0,914, IC 95% 0,845 a 0,986), sem associa&#231;&#227;o significativa com interna&#231;&#245;es (OR 1,003, IC 95% 0,927 a 1,083).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o</title>
          <p>A implanta&#231;&#227;o do SAMU esteve associada a uma redu&#231;&#227;o modesta, mas significativa, na mortalidade intra-hospitalar. Esse achado refor&#231;a o papel fundamental do cuidado pr&#233;-hospitalar no cuidado do IAM e a necessidade de investimentos nesse servi&#231;o para melhorar os desfechos cl&#237;nicos em pa&#237;ses de baixa e m&#233;dia renda.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Infarto do Mioc&#225;rdio</kwd>
        <kwd>Servi&#231;os M&#233;dicos de Emerg&#234;ncia</kwd>
        <kwd>Mortalidade Hospitalar</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FAPEMIG</funding-source>
          <award-id>310790/2021-2</award-id>
          <award-id>PPM-00428-17</award-id>
        </award-group>
        <award-group>
          <funding-source>FAPEMIG</funding-source>
          <award-id>RED-00081-16</award-id>
        </award-group>
        <award-group>
          <funding-source>CNPq</funding-source>
          <award-id>147122/2021-0</award-id>
        </award-group>
        <funding-statement>Fontes de financiamento: O presente estudo foi financiado por CNPq (310790/2021-2), FAPEMIG (PPM-00428-17 e RED-00081-16) e IATS/CNPq [n&#250;mero 147122/2021-0].</funding-statement>
      </funding-group>
      <counts>
        <fig-count count="8"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="35"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>O infarto agudo do mioc&#225;rdio (IAM) continua sendo uma das principais causas de morbimortalidade ao redor do mundo. <sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup> O manejo efetivo dos pacientes com IAM est&#225; diretamente ligado ao tempo para assist&#234;ncia m&#233;dica e aproximadamente metade dos &#243;bitos atribu&#237;dos a IAM resultam de parada card&#237;aca fora do hospital, refor&#231;ando a import&#226;ncia do atendimento pr&#233;-hospitalar e do desenvolvimento de sistemas de aten&#231;&#227;o para IAM baseados em evid&#234;ncias.</p>
      <p>Especificamente, em rela&#231;&#227;o ao infarto do mioc&#225;rdio com supradesnivelamento do segmento ST, o diagn&#243;stico precoce e a terapia de reperfus&#227;o adequada s&#227;o de extrema import&#226;ncia para a redu&#231;&#227;o da mortalidade. A interven&#231;&#227;o coron&#225;ria percut&#226;nea (ICP) prim&#225;ria, primeira escolha para reperfus&#227;o, quando dispon&#237;vel, &#233; mais eficaz do que a terapia trombol&#237;tica, mas idealmente deve ser realizada at&#233; 120 minutos ap&#243;s o primeiro contato m&#233;dico, ou em at&#233; 90 minutos se o paciente for atendido em uma unidade capaz de PCI prim&#225;ria. A tromb&#243;lise &#233; mais eficaz quando administrada dentro de 3 horas do in&#237;cio dos sintomas. Qualquer uma das estrat&#233;gias deve ser administrada em at&#233; 12 horas ap&#243;s o in&#237;cio dos sintomas. <sup><xref ref-type="bibr" rid="B3">3</xref></sup> Na pr&#225;tica cl&#237;nica, uma propor&#231;&#227;o significativa de pacientes n&#227;o recebe atendimento que cumpra essas metas de tempo e a situa&#231;&#227;o &#233; ainda pior em comunidades rurais e &#225;reas com poucos recursos. <sup><xref ref-type="bibr" rid="B3">3</xref> - <xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>Ainda faltam dados contempor&#226;neos sobre o impacto do uso do atendimento pr&#233;-hospitalar no cen&#225;rio do IAM, especialmente em pa&#237;ses de baixa e m&#233;dia renda, principalmente na perspectiva mais generaliz&#225;vel de uma investiga&#231;&#227;o de base comunit&#225;ria, bem como informa&#231;&#245;es sobre os resultados hospitalares de pacientes transportados por ambul&#226;ncia. No entanto, sabe-se que os primeiros minutos ap&#243;s o in&#237;cio do IAM s&#227;o cruciais para o progn&#243;stico e sobrevida do paciente e, considerando isso, &#233; importante avaliar objetivamente os poss&#237;veis impactos do atendimento pr&#233;-hospitalar de emerg&#234;ncia no manejo e nos desfechos do IAM. <sup><xref ref-type="bibr" rid="B8">8</xref></sup> Por&#233;m, &#233; dif&#237;cil obter esse tipo de informa&#231;&#227;o a partir de estudos observacionais, pois n&#227;o h&#225; controle sobre a classifica&#231;&#227;o das vari&#225;veis estudadas e, muitas vezes, &#233; dif&#237;cil isolar a vari&#225;vel dependente.</p>
      <p>Portanto, objetivamos avaliar os impactos da implanta&#231;&#227;o do Servi&#231;o de Atendimento M&#233;dico de Urg&#234;ncia (SAMU) nas taxas de interna&#231;&#227;o e na mortalidade geral e hospitalar por IAM no estado de Minas Gerais (MG), na Regi&#227;o Sudeste do Brasil.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <p>Trata-se de um estudo observacional, retrospectivo e ecol&#243;gico, que avaliou dados do Sistema &#218;nico de Sa&#250;de (SUS, DataSUS TabNET), <sup><xref ref-type="bibr" rid="B9">9</xref></sup> de todos os 853 munic&#237;pios do estado de MG, no per&#237;odo de 2008 a 2016, de acordo com a declara&#231;&#227;o RECORD para estudos que usam dados de sa&#250;de coletados rotineiramente. <sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
      <p>MG &#233; o estado com maior n&#250;mero de munic&#237;pios (853) no Brasil, estando localizado na Regi&#227;o Sudeste do Brasil. &#201; o segundo estado mais populoso do Brasil, com 21 milh&#245;es de habitantes distribu&#237;dos em uma &#225;rea compar&#225;vel &#224; da Fran&#231;a. O &#205;ndice de Desenvolvimento Humano (IDH) m&#233;dio &#233; de 0,731 e 14,46% da popula&#231;&#227;o &#233; considerada pobre ou muito pobre, segundo o Instituto Brasileiro de Geografia e Estat&#237;stica (IBGE). <sup><xref ref-type="bibr" rid="B11">11</xref></sup> MG pode ser considerada representativa do pa&#237;s, pois a distribui&#231;&#227;o et&#225;ria, o percentual de urbaniza&#231;&#227;o e a desigualdade social s&#227;o semelhantes ao padr&#227;o nacional geral. As regi&#245;es norte e nordeste de MG apresentam os menores IDH, semelhantes &#224;s regi&#245;es Norte e Nordeste do Brasil, enquanto as regi&#245;es oeste e sul do estado apresentam IDH semelhante &#224;s &#225;reas de maior IDH do pa&#237;s. <sup><xref ref-type="bibr" rid="B10">10</xref> - <xref ref-type="bibr" rid="B12">12</xref></sup></p>
      <p>O servi&#231;o nacional de ambul&#226;ncias, denominado SAMU, foi implantado no estado de MG em 2003 por um programa nacional denominado &#8220;Pol&#237;tica Nacional das Urg&#234;ncias&#8221;. O programa teve in&#237;cio em alguns munic&#237;pios selecionados, que ficaram respons&#225;veis pela gest&#227;o de seu pr&#243;prio sistema. A partir de 2009 foram criados sistemas de atendimento pr&#233;-hospitalar regionalizado, denominados &#8220;cons&#243;rcios&#8221;, que atualmente correspondem ao modelo principal de atendimento e abrangem diversas regi&#245;es do estado. No per&#237;odo analisado, havia 5 cons&#243;rcios no estado: Cons&#243;rcio Intermunicipal de Sa&#250;de da Macrorregi&#227;o do Sul de Minas (CISSUL), Cons&#243;rcio Intermunicipal de Sa&#250;de da Regi&#227;o Sudeste (CISDESTE), Cons&#243;rcio Intermunicipal de Sa&#250;de da Rede de Urg&#234;ncia Centro Sul (CISRU), Urg&#234;ncia do Norte de Minas (CISRUN) e Cons&#243;rcio Intermunicipal de Sa&#250;de Rede de Urg&#234;ncia Macro Nordeste/Jequitinhonha (CISNORJE), abrangendo 469 munic&#237;pios nas regi&#245;es sul, sudeste, centro-sul, norte e nordeste, respectivamente ( <xref ref-type="fig" rid="f01">Figura 1</xref> ).</p>
      <p>
        <fig id="f01">
          <label>Figura 1</label>
          <caption>
            <title>Distribui&#231;&#227;o de SAMUs municipais e cons&#243;rcios de SAMU em Minas Gerais. Acr&#244;nimos: CISDESTE: Cons&#243;rcio Intermunicipal de Sa&#250;de da Regi&#227;o Sudeste; CISNORJE: Cons&#243;rcio Intermunicipal de Sa&#250;de Rede de Urg&#234;ncia Macro Nordeste/Jequitinhonha; CISRU: Cons&#243;rcio Intermunicipal de Sa&#250;de da Rede de Urg&#234;ncia Centro-Sul; CISRUN: Cons&#243;rcio Intermunicipal de Sa&#250;de da Rede de Urg&#234;ncia do Norte de Minas; CISSUL: Cons&#243;rcio Intermunicipal de Sa&#250;de da Macrorregi&#227;o do Sul de Minas; SAMU: Servi&#231;o de Atendimento M&#233;dico de Urg&#234;ncia. Fonte: SES-MH 2016.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf01.tif"/></fig>
      </p>
      <p>As datas de implanta&#231;&#227;o do SAMU foram obtidas junto ao governo estadual e coordenadores locais do SAMU. O primeiro cons&#243;rcio intermunicipal foi implantado em 2009.Em 2011, foi implantado um, em 2012, dois e em 2015, mais um. Alguns servi&#231;os foram implantados antes do per&#237;odo analisado, enquanto outros foram implantados no per&#237;odo do estudo. Ao mesmo tempo, alguns munic&#237;pios j&#225; haviam implantado cons&#243;rcios de SAMU no in&#237;cio da an&#225;lise, enquanto outros implantaram o SAMU durante o per&#237;odo do estudo e outros n&#227;o possu&#237;am SAMU durante esse per&#237;odo. Catorze munic&#237;pios possu&#237;am SAMU no per&#237;odo analisado (SAMU municipais). O SAMU foi implantado em 86 munic&#237;pios em janeiro de 2009 (CISRUN), em 94 munic&#237;pios em novembro de 2014 (CISDESTE), em 86 munic&#237;pios em abril de 2012 (CISNORJE), em 51 munic&#237;pios em junho de 2012 (CISRU) e em 152 munic&#237;pios em julho de 2015 (CISSUL). Os demais munic&#237;pios do estado (n = 370) permaneceram sem SAMU durante todo o per&#237;odo do estudo. A <inline-supplementary-material mime-subtype="pdf" mimetype="application" xlink:href="">Figura Suplementar 1</inline-supplementary-material> mostra a evolu&#231;&#227;o da cobertura do SAMU no estado, &#224; medida que cada cons&#243;rcio regional foi implementado.</p>
      <p>Os desfechos de interesse foram as taxas de mortalidade geral e intra-hospitalar por IAM e taxa de interna&#231;&#245;es por IAM, avaliadas no per&#237;odo de 2008 a 2016. A escolha desses desfechos justifica-se pelo fato de serem de maior relev&#226;ncia cl&#237;nica e epidemiol&#243;gica e de maior potencial de associa&#231;&#227;o com a implanta&#231;&#227;o do SAMU, al&#233;m das altas taxas de preenchimento, enquanto vari&#225;veis obrigat&#243;rias.</p>
      <p>Os dados sobre a popula&#231;&#227;o de cada munic&#237;pio foram obtidos do IBGE, o Instituto Demogr&#225;fico e Estat&#237;stico oficial do Brasil. <sup><xref ref-type="bibr" rid="B13">13</xref></sup> Para &#243;bitos e interna&#231;&#245;es, os dados foram extra&#237;dos do DATASUS TabNET, <sup><xref ref-type="bibr" rid="B9">9</xref></sup> um banco de dados eletr&#244;nico que coleta informa&#231;&#245;es em n&#237;vel de paciente do SUS. Foram utilizadas informa&#231;&#245;es de ocorr&#234;ncias mensais desses desfechos, das bases de dados do Sistema de Informa&#231;&#245;es sobre Mortalidade (SIM) e do Sistema de Informa&#231;&#245;es Hospitalares (SIH), respectivamente, para a popula&#231;&#227;o dos 853 munic&#237;pios de MG, de 2008 a 2016. <sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
      <p>Os &#243;bitos foram considerados &#243;bitos por IAM quando a causa principal do &#243;bito apresentava os seguintes c&#243;digos da CID-10 (I21 a I24): I21 &#8220;infarto agudo do mioc&#225;rdio&#8221;, I22 &#8220;infarto do mioc&#225;rdio recorrente&#8221;, I23 &#8220;algumas complica&#231;&#245;es atuais subsequentes a infarto agudo do mioc&#225;rdio&#8221;, I24 &#8220;outras cardiopatias isqu&#234;micas agudas&#8221;. Os dados do SIH foram utilizados para obten&#231;&#227;o dos dados das interna&#231;&#245;es por IAM: procedimento &#8220;tratamento do IAM&#8221;, c&#243;digo SIH/DATASUS 03.03.06.019-0 e &#8220;angioplastia coron&#225;ria prim&#225;ria&#8221;, c&#243;digo 040.603.004-9. Neste estudo, a mortalidade intra-hospitalar por IAM foi calculada a partir do n&#250;mero de &#243;bitos pelos c&#243;digos citados, dividido pelo n&#250;mero de interna&#231;&#245;es por esses mesmos c&#243;digos em cada munic&#237;pio por m&#234;s de an&#225;lise.</p>
      <p>Como o estudo utilizou dados p&#250;blicos dispon&#237;veis na plataforma DATASUS, n&#227;o foi necess&#225;ria a aprova&#231;&#227;o por um comit&#234; de &#233;tica em pesquisa.</p>
      <sec>
        <title>An&#225;lise de dados</title>
        <p>Foi utilizado o software R vers&#227;o 3.3.4 para an&#225;lise estat&#237;stica. <sup><xref ref-type="bibr" rid="B15">15</xref></sup> A unidade de an&#225;lise foi o munic&#237;pio. Foi realizada uma an&#225;lise mensal dos desfechos, de janeiro de 2008 a dezembro de 2016, para cada um dos 853 munic&#237;pios de MG, considerando a popula&#231;&#227;o por estimativas de cada ano. <sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
        <p>Os 3 desfechos foram ajustados pela estrutura et&#225;ria, com base na popula&#231;&#227;o de 2010. <sup><xref ref-type="bibr" rid="B11">11</xref></sup> As taxas foram estimadas para cada munic&#237;pio e m&#234;s considerando o ajuste por idade. Os munic&#237;pios foram indexados por i = 1, &#8230;, n, onde n = 853 &#233; o n&#250;mero total de munic&#237;pios, enquanto os meses foram indexados por t = 1, &#8230;, T, onde T &#233; o n&#250;mero de meses no per&#237;odo analisado.</p>
        <p>A assimetria excessiva da mortalidade geral e intra-hospitalar por IAM foi suavizada pelo m&#233;todo emp&#237;rico de Bayes. <sup><xref ref-type="bibr" rid="B16">16</xref></sup> O m&#233;todo foi usado para estimar as taxas em vez da abordagem cl&#225;ssica de estimativa de taxas. Na abordagem cl&#225;ssica, a taxa &#233; calculada como a raz&#227;o do n&#250;mero de eventos (&#243;bitos, interna&#231;&#245;es) pela popula&#231;&#227;o sob risco. Portanto, a variabilidade das taxas estimadas &#233; fortemente afetada por pequenas mudan&#231;as no n&#250;mero de eventos (&#243;bitos) quando computados para pequenas &#225;reas onde o valor esperado para eventos &#233; baixo. O m&#233;todo emp&#237;rico de Bayes visa minimizar as varia&#231;&#245;es das taxas estimadas por meio de uma m&#233;dia ponderada entre a taxa municipal e a taxa regional. No presente estudo, a regi&#227;o foi definida como o estado de MG. Os pesos foram interpretados pelo tamanho da popula&#231;&#227;o; quanto maior a popula&#231;&#227;o, menor o peso da taxa de regi&#227;o. As taxas de mortalidade e hospitaliza&#231;&#227;o por IAM foram modeladas usando a distribui&#231;&#227;o de Poisson, enquanto a mortalidade intra-hospitalar por IAM foi pela distribui&#231;&#227;o binomial. Em seguida, foram estimadas pelo m&#233;todo emp&#237;rico de Bayes (<inline-supplementary-material mime-subtype="pdf" mimetype="application" xlink:href="">Figuras Suplementares 2</inline-supplementary-material> e <inline-supplementary-material mime-subtype="pdf" mimetype="application" xlink:href="">3</inline-supplementary-material>). Foram avaliadas as interna&#231;&#245;es com os referidos c&#243;digos de interna&#231;&#227;o do SIH/DATASUS de 2008 a 2016 em todos os munic&#237;pios de MG e, como essa vari&#225;vel tamb&#233;m est&#225; sujeita a varia&#231;&#245;es significativas em munic&#237;pios com pequenas popula&#231;&#245;es, foi utilizado para ajuste o m&#233;todo emp&#237;rico global de Bayes, conforme explicado para an&#225;lise da taxa de mortalidade.</p>
        <p>Foram observadas tend&#234;ncias sazonais e temporais de queda das taxas de mortalidade geral e hospitalar, com tend&#234;ncia semianual na oscila&#231;&#227;o entre as taxas mais baixas e mais altas e redu&#231;&#227;o gradativa das mesmas ao longo do per&#237;odo analisado. Portanto, a sazonalidade e a temporalidade foram inclu&#237;das nos modelos de an&#225;lise estat&#237;stica. O presente estudo avaliou a rela&#231;&#227;o entre a disponibilidade de atendimento do SAMU em cada munic&#237;pio e os seguintes 3 desfechos: mortalidade por IAM na popula&#231;&#227;o geral, mortalidade por IAM intra-hospitalar e n&#250;mero de interna&#231;&#245;es por IAM, utilizando o modelo hier&#225;rquico de Poisson, e as taxas analisadas foram corrigidas pela estrutura et&#225;ria e destendenciadas por influ&#234;ncias temporais e sazonais. Um intervalo de confian&#231;a de 95% (IC) foi usado para todos os resultados.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>As taxas de mortalidade por IAM, ajustadas pela distribui&#231;&#227;o et&#225;ria, apresentaram tend&#234;ncia decrescente ao longo do estudo, variando de 35,7 &#243;bitos por 100.000 habitantes em 2008 a 30,4 &#243;bitos por 100.000 habitantes em 2016, ou seja, cerca de 2% por ano em m&#233;dia ( <xref ref-type="table" rid="t1">Tabela 1</xref> ). Tamb&#233;m foi observada varia&#231;&#227;o sazonal nas taxas de mortalidade por IAM, sendo maior no inverno e menor no ver&#227;o ( <xref ref-type="fig" rid="f02">Figura 2</xref> ).</p>
      <p>
        <table-wrap id="t1">
          <label>Tabela 1</label>
          <caption>
            <title>Taxas anuais de mortalidade, interna&#231;&#227;o e mortalidade intra-hospitalar por IAM, ajustadas por idade, no estado de Minas Gerais, de 2008 a 2016</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Ano</th>
                <th>Mortalidade (por 100.000)</th>
                <th>Mortalidade intra-hospitalar (%)*</th>
                <th>Interna&#231;&#245;es (por 100.000)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>2008</td>
                <td align="center">35,7 (35,3 &#8211; 36,1)</td>
                <td align="center">13,81</td>
                <td align="center">152 (146 - 158)</td>
              </tr>
              <tr>
                <td>2009</td>
                <td align="center">34,1 (33,8 &#8211; 34,5)</td>
                <td align="center">13,65</td>
                <td align="center">150 (144 - 156)</td>
              </tr>
              <tr>
                <td>2010</td>
                <td align="center">35,0 (34,6 &#8211; 35,3)</td>
                <td align="center">13,78</td>
                <td align="center">140 (134 - 145)</td>
              </tr>
              <tr>
                <td>2011</td>
                <td align="center">33,8 (33,4 &#8211; 34,1)</td>
                <td align="center">11,82</td>
                <td align="center">147 (142 - 152)</td>
              </tr>
              <tr>
                <td>2012</td>
                <td align="center">32,4 (32,1 &#8211; 32,6)</td>
                <td align="center">11,29</td>
                <td align="center">146 (141 - 151)</td>
              </tr>
              <tr>
                <td>2013</td>
                <td align="center">31,9 (31,7 &#8211; 32,2)</td>
                <td align="center">11,99</td>
                <td align="center">142 (137 - 146)</td>
              </tr>
              <tr>
                <td>2014</td>
                <td align="center">30,9 (30,6 &#8211; 31,1)</td>
                <td align="center">12,15</td>
                <td align="center">137 (132 - 141)</td>
              </tr>
              <tr>
                <td>2015</td>
                <td align="center">29,9 (29,7 &#8211; 30,2)</td>
                <td align="center">10,82</td>
                <td align="center">138 (133 - 142)</td>
              </tr>
              <tr>
                <td>2016</td>
                <td align="center">30,4 (30,1 &#8211; 30,6)</td>
                <td align="center">11,43</td>
                <td align="center">147 (142 - 151)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>
                <italic>*As taxas s&#227;o expressas com intervalo de confian&#231;a de 95%.</italic>
              </p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </p>
      <p>
        <fig id="f02">
          <label>Figura 2</label>
          <caption>
            <title>Ocorr&#234;ncia de varia&#231;&#227;o sazonal nas taxas de mortalidade de 2008 a 2016. Uma maior taxa de mortalidade &#233; observada durante o inverno e taxas mais baixas s&#227;o observadas durante o ver&#227;o.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf02.tif"/></fig>
      </p>
      <p>A mortalidade intra-hospitalar por IAM corrigida pela idade tamb&#233;m apresentou tend&#234;ncia decrescente, de 13,81% em 2008 para 11,43% em 2016 ( <xref ref-type="table" rid="t1">Tabela 1</xref> ), com amplas varia&#231;&#245;es mensais e padr&#227;o sazonal, embora menos evidente quando comparada &#224; taxa de mortalidade por IAM ( <xref ref-type="fig" rid="f03">Figura 3</xref> ).</p>
      <p>
        <fig id="f03">
          <label>Figura 3</label>
          <caption>
            <title>Taxas de letalidade e mortalidade mensais para os munic&#237;pios de Minas Gerais, de 2008 a 2016. Os pontos verdes representam taxas mensais de letalidade para toda a popula&#231;&#227;o analisada, que apresenta varia&#231;&#227;o mensal consider&#225;vel sem padr&#227;o sazonal definido. A linha vermelha representa a tend&#234;ncia da taxa ao longo do tempo, com uma redu&#231;&#227;o acentuada de 2008 para 2012, estagna&#231;&#227;o em 2013 e uma nova redu&#231;&#227;o mais lenta de 2014 para 2016. Observamos que a implanta&#231;&#227;o do Servi&#231;o de Atendimento M&#233;dico de Urg&#234;ncia (SAMU), representado pelas linhas verticais azuis, n&#227;o teve influ&#234;ncia clara na letalidade na an&#225;lise descritiva.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf03.tif"/></fig>
      </p>
      <p>A implanta&#231;&#227;o do SAMU foi associada &#224; diminui&#231;&#227;o da mortalidade por IAM ( <italic>odds ratio</italic> [OR] = 0,967, IC 95% 0,936 a 0,998) e mortalidade intra-hospitalar por IAM (OR = 0,914, IC 95% 0,845 a 0,986), sem associa&#231;&#227;o significativa com o n&#250;mero de interna&#231;&#245;es (OR 1,003, IC 95% 0,927 a 1,083). N&#227;o houve varia&#231;&#227;o sazonal no n&#250;mero de interna&#231;&#245;es por IAM durante o per&#237;odo do estudo.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>No presente estudo, foi observado que a implanta&#231;&#227;o do SAMU no estado brasileiro de MG esteve associada &#224; redu&#231;&#227;o das taxas gerais de mortalidade por IAM. A mortalidade intra-hospitalar por IAM corrigida pela idade tamb&#233;m apresentou tend&#234;ncia decrescente ao longo do tempo, com padr&#227;o sazonal. No entanto, n&#227;o foi encontrada associa&#231;&#227;o significativa com as taxas de interna&#231;&#227;o por IAM no per&#237;odo analisado.</p>
      <p>Apesar da falta de evid&#234;ncias em pa&#237;ses em desenvolvimento, esses resultados est&#227;o de acordo com estudos desenvolvidos em pa&#237;ses de alta renda, e provavelmente est&#227;o relacionados ao maior acesso do paciente a algum tipo de tratamento do IAM e &#224; diminui&#231;&#227;o do tempo entre o in&#237;cio dos sintomas e o in&#237;cio da terapia espec&#237;fica, incluindo reperfus&#227;o quando indicada. <sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B17">17</xref> , <xref ref-type="bibr" rid="B18">18</xref></sup> Por outro lado, alguns estudos n&#227;o conseguiram demonstrar associa&#231;&#227;o entre a implanta&#231;&#227;o de sistemas de aten&#231;&#227;o ao IAM e diminui&#231;&#227;o da mortalidade, apesar da melhora na qualidade da assist&#234;ncia, ades&#227;o &#224;s recomenda&#231;&#245;es guiadas por diretrizes e tempo de tratamento reduzidos. <sup><xref ref-type="bibr" rid="B3">3</xref> - <xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B12">12</xref> , <xref ref-type="bibr" rid="B19">19</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup> Isso ocorreu mesmo com o uso de protocolos elaborados com m&#250;ltiplas interven&#231;&#245;es al&#233;m do atendimento pr&#233;-hospitalar. Dentre esses estudos, destaca-se o Reperfusion of Acute myocardial infarction in North Carolina Emergency departments (RACE). Foi realizado no estado da Carolina do Norte, EUA, levando &#224; redu&#231;&#227;o do tempo de consulta e dos atrasos na administra&#231;&#227;o do tratamento de reperfus&#227;o ap&#243;s a implanta&#231;&#227;o e sistematiza&#231;&#227;o de protocolos de atendimento ao paciente com IAM. <sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
      <p>Diferentemente de relatos anteriores, nosso estudo foi realizado em um pa&#237;s de renda m&#233;dia, fato que pode ajudar a explicar nossos resultados positivos em termos de desfechos duros. Em estudos realizados em pa&#237;ses desenvolvidos, a qualidade de linha de base do atendimento ao IAM &#233; geralmente superior &#224; observada em nosso pa&#237;s. <sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup> Assim, demonstrar a magnitude do benef&#237;cio incremental de qualquer interven&#231;&#227;o &#233; mais dif&#237;cil nessa situa&#231;&#227;o, enquanto em locais onde h&#225; baixa qualidade e presta&#231;&#227;o de cuidados, interven&#231;&#245;es menos complexas podem ter um impacto maior nos resultados. Uma avalia&#231;&#227;o pr&#233;via da ades&#227;o aos crit&#233;rios de qualidade da aten&#231;&#227;o ao IAM em Minas Gerais ilustra essa lacuna assistencial na regi&#227;o. <sup><xref ref-type="bibr" rid="B21">21</xref> - <xref ref-type="bibr" rid="B23">23</xref></sup> Apesar da implanta&#231;&#227;o do atendimento pr&#233;-hospitalar n&#227;o fazer parte da implementa&#231;&#227;o dos sistemas de aten&#231;&#227;o ao IAM, as unidades intervencionistas ou unidades especializadas em cardiologia nessas regi&#245;es, pode ter influenciado na melhora da qualidade do atendimento no per&#237;odo do estudo, uma vez que maior propor&#231;&#227;o de pacientes pode ter recebido diagn&#243;stico preciso e tratamento adequado.</p>
      <p>Os desfechos associados ao IAM est&#227;o relacionados a m&#250;ltiplas vari&#225;veis, principalmente a estrutura para o atendimento dos pacientes. <sup><xref ref-type="bibr" rid="B22">22</xref> - <xref ref-type="bibr" rid="B24">24</xref></sup> Vale destacar alguns elementos relevantes na formula&#231;&#227;o de uma rede de alta complexidade em cardiologia: 1) a rela&#231;&#227;o inversa entre o tamanho e volume de procedimentos realizados em hospitais de refer&#234;ncia e mortalidade por IAM; 2) benef&#237;cio da estrat&#233;gia &#8220;farmaco-invasiva&#8221;, que consiste em fibrin&#243;lise pr&#233;-hospitalar ou intra-hospitalar precoce seguida de ICP de rotina entre 3 e 24 horas, compar&#225;vel &#224; ICP prim&#225;ria em pacientes com sintomas de IAM de curta dura&#231;&#227;o, sempre que for poss&#237;vel a transfer&#234;ncia oportuna para unidades com capacidade de ICP; <sup><xref ref-type="bibr" rid="B19">19</xref></sup> 3) custo-efetividade da expans&#227;o do atendimento pr&#233;-hospitalar em rela&#231;&#227;o &#224; constru&#231;&#227;o de novos servi&#231;os de cardiologia intervencionista, que foi demonstrada nos EUA, onde a dist&#226;ncia at&#233; os servi&#231;os de hemodin&#226;mica &#233; em torno de 70 km na grande maioria dos locais. <sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup></p>
      <p>Como esperado, houve maior varia&#231;&#227;o de taxas em locais com menor popula&#231;&#227;o, como nas regi&#245;es leste e centro-sul do estado, que possuem os menores IDH do estado, respectivamente cobertos pelos cons&#243;rcios CISDESTE e CISRU. Esse achado possivelmente est&#225; associado a menor qualidade do preenchimento da declara&#231;&#227;o de &#243;bito, com maior propor&#231;&#227;o de &#243;bitos por causas indefinidas e &#8220;c&#243;digos lixo&#8221; (condi&#231;&#245;es de sa&#250;de que n&#227;o podem ser diretamente atribu&#237;veis &#224; mortalidade), associados &#224; influ&#234;ncia de outras causas de mortalidade nessas popula&#231;&#245;es, como as doen&#231;as infecciosas, condizente com o observado em outras regi&#245;es de baixo IDH no Brasil e mundialmente (OMS, 2017). <sup><xref ref-type="bibr" rid="B24">24</xref> - <xref ref-type="bibr" rid="B26">26</xref></sup> Esse achado reitera a import&#226;ncia do uso de m&#233;todos de ajuste anal&#237;tico para varia&#231;&#245;es extremas. Nesse sentido, a an&#225;lise metodol&#243;gica com a aplica&#231;&#227;o do m&#233;todo de Bayes emp&#237;rico global foi eficaz em reduzir a varia&#231;&#227;o das taxas em pequenas popula&#231;&#245;es, sem alterar os valores em locais com maiores popula&#231;&#245;es, conforme mostra a <xref ref-type="fig" rid="f04">Figura 4</xref> . A utiliza&#231;&#227;o das taxas observadas no estado de MG como refer&#234;ncia para suaviza&#231;&#227;o permitiu que esse processo fosse feito com uma popula&#231;&#227;o de refer&#234;ncia semelhante aos munic&#237;pios analisados, mas com uma popula&#231;&#227;o maior.</p>
      <p>
        <fig id="f04">
          <label>Figura 4</label>
          <caption>
            <title>Taxas anuais de mortalidade bruta no estado de Minas Gerais de 2008 a 2016. Uma tend&#234;ncia de redu&#231;&#227;o temporal.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf04.tif"/></fig>
      </p>
      <p>Com rela&#231;&#227;o &#224; varia&#231;&#227;o sazonal das taxas de mortalidade por IAM, essa varia&#231;&#227;o n&#227;o era esperada em uma regi&#227;o com varia&#231;&#227;o de temperatura muito menor em compara&#231;&#227;o com pa&#237;ses da Am&#233;rica do Norte ou da Europa, ou mesmo com regi&#245;es mais frias do Brasil, como S&#227;o Paulo e a Regi&#227;o Sul. Levanta a possibilidade de outras explica&#231;&#245;es al&#233;m da temperatura, ou altera&#231;&#245;es fisiol&#243;gicas relacionadas &#224; temperatura, como altera&#231;&#245;es na viscosidade do sangue, volume plaquet&#225;rio e press&#227;o arterial. <sup><xref ref-type="bibr" rid="B27">27</xref></sup> Outras doen&#231;as mais comuns durante o inverno, especialmente infec&#231;&#245;es respirat&#243;rias por v&#237;rus e pneumonia adquirida na comunidade demonstrou afetar o sistema cardiovascular de v&#225;rias maneiras e precipitar desfechos card&#237;acos adversos, como insufici&#234;ncia card&#237;aca, infarto do mioc&#225;rdio e arritmias card&#237;acas. <sup><xref ref-type="bibr" rid="B28">28</xref></sup> Como a doen&#231;a arterial coronariana &#233; essencialmente uma doen&#231;a inflamat&#243;ria, foi demonstrado que a inflama&#231;&#227;o relacionada a pat&#243;genos respirat&#243;rios pode desencade&#225;-la. <sup><xref ref-type="bibr" rid="B29">29</xref></sup> Em uma s&#233;rie de casos autocontrolados usando dados nacionais de vigil&#226;ncia de infec&#231;&#245;es, vinculada ao Scottish Morbidity Record, as taxas de IAM e acidente vascular cerebral aumentaram substancialmente na semana seguinte a uma infec&#231;&#227;o respirat&#243;ria. <sup><xref ref-type="bibr" rid="B30">30</xref></sup> Al&#233;m disso, uma meta-an&#225;lise recente mostrou o impacto da vacina pneumoc&#243;cica polissacar&#237;dica 23-valente em fornecer prote&#231;&#227;o contra qualquer evento cardiovascular ( <italic>risk ratio</italic> [RR]: 0,91; IC 95%: 0,84 a 0,99), infarto do mioc&#225;rdio (RR: 0,88; IC 95%: 0,79 a 0,98) e mortalidade por todas as causas (RR: 0,78; IC 95%: 0,68 a 0,88) em indiv&#237;duos de todas as faixas et&#225;rias. <sup><xref ref-type="bibr" rid="B31">31</xref></sup> Por outro lado, um ensaio cl&#237;nico em andamento realizado no Brasil comparando vacina contra influenza em dose &#250;nica e em dose dupla ap&#243;s um evento coronariano agudo foi interrompido precocemente devido &#224; aparente falta de benef&#237;cio nas an&#225;lises provis&#243;rias. <sup><xref ref-type="bibr" rid="B32">32</xref></sup></p>
      <p>A polui&#231;&#227;o do ar, especialmente a exposi&#231;&#227;o ao material particulado, tamb&#233;m tem sido associada a um maior risco de doen&#231;as cardiovasculares, incluindo IAM. <sup><xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B34">34</xref></sup> Um estudo recente observou que um aumento de cerca de 10 microgramas por m <sup>3</sup> de ar foi associado a um aumento de 16% de mortalidade por IAM. <sup><xref ref-type="bibr" rid="B33">33</xref></sup> Enquanto isso, outro estudo usando um modelo global de qu&#237;mica atmosf&#233;rica mostrou que mais de 60% das mortes cardiovasculares ao redor do mundo est&#227;o relacionadas &#224; polui&#231;&#227;o do ar, e aumentos de curto prazo na polui&#231;&#227;o do ar est&#227;o associados ao IAM. <sup><xref ref-type="bibr" rid="B34">34</xref></sup> Sunyer et al., observaram que o aumento dos n&#237;veis de di&#243;xido de enxofre no ar de sete cidades europeias aumentou as interna&#231;&#245;es por doen&#231;as cardiovasculares no dia anterior e no dia de maior teor de poluentes. <sup><xref ref-type="bibr" rid="B35">35</xref></sup> Essa associa&#231;&#227;o permaneceu significativa mesmo ap&#243;s o ajuste para part&#237;culas com tamanho inferior a 10 &#956;m entre indiv&#237;duos com menos de 65 anos. A polui&#231;&#227;o do ar tende a ser maior nos meses em que os n&#237;veis de chuva s&#227;o mais baixos. Portanto, no Brasil, onde os ver&#245;es s&#227;o chuvosos e os invernos predominantemente mais secos, a sazonalidade pode, de fato, ter um papel importante na mortalidade por IAM.</p>
      <p>Nosso estudo tem algumas limita&#231;&#245;es que devem ser mencionadas. A implementa&#231;&#227;o do atendimento pr&#233;-hospitalar &#233; acompanhada de co-interven&#231;&#245;es, como a articula&#231;&#227;o da vincula&#231;&#227;o das institui&#231;&#245;es de sa&#250;de do sistema de aten&#231;&#227;o ao IAM e aumento dos servi&#231;os locais de emerg&#234;ncia, que n&#227;o foram sistematicamente estudados nesta pesquisa e podem ter influenciado os achados. Por meio de informa&#231;&#245;es p&#250;blicas disponibilizadas pelo Minist&#233;rio da Sa&#250;de, Secretaria de Estado de Sa&#250;de de Minas Gerais, Secretarias Municipais de Sa&#250;de e bancos de dados dos SAMUs, &#233; poss&#237;vel afirmar que as redes dispon&#237;veis eram incipientes e que havia falta de infraestrutura, insumos, recursos humanos e processos organizacionais e de administra&#231;&#227;o na maior parte do estado e do pa&#237;s. <sup><xref ref-type="bibr" rid="B11">11</xref> , <xref ref-type="bibr" rid="B13">13</xref> , <xref ref-type="bibr" rid="B14">14</xref></sup> Exemplos incluem a baixa disponibilidade de servi&#231;os de cardiologia intervencionista e a concentra&#231;&#227;o de recursos de sa&#250;de em regi&#245;es com melhores perfis sociodemogr&#225;ficos; a baixa utiliza&#231;&#227;o dos servi&#231;os de telessa&#250;de pelas equipes pr&#233;-hospitalares; a aus&#234;ncia de fibrinol&#237;ticos nas ambul&#226;ncias do SAMU; a falta de protocolos cl&#237;nicos e padroniza&#231;&#227;o de cuidados baseados em evid&#234;ncias; a infraestrutura prec&#225;ria da maioria dos departamentos de emerg&#234;ncia do estado, principalmente unidades de emerg&#234;ncia pr&#233;-hospitalar e hospitais de pequeno porte; e o treinamento insuficiente do pessoal de sa&#250;de envolvido no atendimento de emerg&#234;ncia. Por fim, esses fatores somam-se &#224; dificuldade de implanta&#231;&#227;o das redes de aten&#231;&#227;o &#224; sa&#250;de por motivos financeiros e pol&#237;ticos.</p>
      <p>O presente estudo n&#227;o abordou o impacto de outros n&#237;veis de aten&#231;&#227;o nos desfechos estudados, como a aten&#231;&#227;o prim&#225;ria &#224; sa&#250;de (APS). Embora existam dados consistentes na literatura mostrando o papel fundamental da APS na preven&#231;&#227;o, promo&#231;&#227;o e tratamento de condi&#231;&#245;es de sa&#250;de que s&#227;o fatores de risco para IAM, com sua capacidade de reduzir as taxas de incid&#234;ncia de IAM, o foco deste estudo foram eventos agudos que ocorrem, embora em propor&#231;&#227;o menor, em sistemas de APS bem estabelecidos. <sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref> , <xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup> Como os efeitos na sa&#250;de associados &#224; APS s&#227;o tipicamente observados a longo prazo, n&#227;o foi feito ajuste para essa vari&#225;vel, dadas as dificuldades t&#233;cnicas inerentes a esse processo e a escassez de bases de dados para realiz&#225;-lo.</p>
      <p>Outra limita&#231;&#227;o est&#225; relacionada ao fato de o modelo ecol&#243;gico n&#227;o incluir vari&#225;veis cl&#237;nicas individuais relevantes; portanto, n&#227;o &#233; poss&#237;vel estabelecer rela&#231;&#245;es entre tais caracter&#237;sticas e os desfechos estudados ou estabelecer uma rela&#231;&#227;o causal definitiva entre a implanta&#231;&#227;o do SAMU e esses desfechos. Finalmente, como todos os estudos observacionais, o risco de vi&#233;s foi minimizado, mas n&#227;o pode ser completamente exclu&#237;do, em particular o vi&#233;s de confus&#227;o residual.</p>
      <p>No entanto, o maior ponto forte do nosso estudo &#233; sua contribui&#231;&#227;o metodol&#243;gica, ou seja, apresenta um m&#233;todo capaz de levar em conta a sazonalidade e as tend&#234;ncias temporais para observar o efeito de uma interven&#231;&#227;o. A tend&#234;ncia temporal de redu&#231;&#227;o da mortalidade foi considerada na an&#225;lise e foi observada a redu&#231;&#227;o da mortalidade com a implanta&#231;&#227;o do SAMU independentemente dessa tend&#234;ncia temporal.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>No presente estudo, observou-se uma pequena redu&#231;&#227;o nas taxas de mortalidade geral e hospitalar atribu&#237;veis ao IAM ap&#243;s a implanta&#231;&#227;o do SAMU em MG no per&#237;odo analisado, sem altera&#231;&#245;es significativas nas taxas de interna&#231;&#227;o hospitalar. Os resultados sugerem que o atendimento pr&#233;-hospitalar desempenha um papel importante no sistema de sa&#250;de, especialmente considerando a crescente carga de doen&#231;as cardiovasculares, especialmente s&#237;ndromes coronarianas agudas.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017;70(1):1-25. doi: 10.1016/j.jacc.2017.04.052.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Roth</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Johnson</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Abajobir</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Abd-Allah</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Abera</surname>
              <given-names>SF</given-names>
            </name>
            <name>
              <surname>Abyu</surname>
              <given-names>G</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2017</year>
          <volume>70</volume>
          <issue>1</issue>
          <fpage>1</fpage>
          <lpage>25</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2017.04.052</pub-id>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135(10):146-603. doi: 10.1161/CIR.0000000000000485.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Benjamin</surname>
              <given-names>EJ</given-names>
            </name>
            <name>
              <surname>Blaha</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Chiuve</surname>
              <given-names>SE</given-names>
            </name>
            <name>
              <surname>Cushman</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Das</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Deo</surname>
              <given-names>R</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association</article-title>
          <source>Circulation</source>
          <year>2017</year>
          <volume>135</volume>
          <issue>10</issue>
          <fpage>146</fpage>
          <lpage>603</lpage>
          <pub-id pub-id-type="doi">10.1161/CIR.0000000000000485</pub-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3. Marino BCA, Marcolino MS, Reis RS Jr, Fran&#231;a AL, Passos PF, Lemos TR, et al. Epidemiological Profile and Quality Indicators in Patients with Acute Coronary Syndrome in Northern Minas Gerais - Minas Telecardio 2 Project. Arq Bras Cardiol. 2016;107(2):106-15. doi: 10.5935/abc.20160095.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marino</surname>
              <given-names>BCA</given-names>
            </name>
            <name>
              <surname>Marcolino</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Reis</surname>
              <given-names>RS</given-names>
              <suffix>Jr</suffix>
            </name>
            <name>
              <surname>Fran&#231;a</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>Passos</surname>
              <given-names>PF</given-names>
            </name>
            <name>
              <surname>Lemos</surname>
              <given-names>TR</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Epidemiological Profile and Quality Indicators in Patients with Acute Coronary Syndrome in Northern Minas Gerais - Minas Telecardio 2 Project</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2016</year>
          <volume>107</volume>
          <issue>2</issue>
          <fpage>106</fpage>
          <lpage>115</lpage>
          <issue-id pub-id-type="doi">10.5935/abc.20160095</issue-id>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4. Marino BCA, Ribeiro ALP, Alkmim MB, Antunes AP, Boersma E, Marcolino MS. Coordinated Regional Care of Myocardial Infarction in a Rural Area in Brazil: Minas Telecardio Project 2. Eur Heart J Qual Care Clin Outcomes. 2016;2(3):215-24. doi: 10.1093/ehjqcco/qcw020. PMID: 29474619.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marino</surname>
              <given-names>BCA</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>ALP</given-names>
            </name>
            <name>
              <surname>Alkmim</surname>
              <given-names>MB</given-names>
            </name>
            <name>
              <surname>Antunes</surname>
              <given-names>AP</given-names>
            </name>
            <name>
              <surname>Boersma</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Marcolino</surname>
              <given-names>MS</given-names>
            </name>
          </person-group>
          <article-title>Coordinated Regional Care of Myocardial Infarction in a Rural Area in Brazil: Minas Telecardio Project 2</article-title>
          <source>Eur Heart J Qual Care Clin Outcomes</source>
          <year>2016</year>
          <volume>2</volume>
          <issue>3</issue>
          <fpage>215</fpage>
          <lpage>224</lpage>
          <issue-id pub-id-type="doi">10.1093/ehjqcco/qcw020</issue-id>
          <comment>PMID: 29474619</comment>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5. Jordan M, Caesar J. Improving Door-to-needle Times for Patients Presenting with ST-Elevation Myocardial Infarction at a Rural District General Hospital. BMJ Qual Improv Rep. 2016;5(1):u209049.w6736. doi: 10.1136/bmjquality.u209049.w6736.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Jordan</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Caesar</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Improving Door-to-needle Times for Patients Presenting with ST-Elevation Myocardial Infarction at a Rural District General Hospital</article-title>
          <source>BMJ Qual Improv Rep</source>
          <year>2016</year>
          <volume>5</volume>
          <issue>1</issue>
          <fpage>u209049.w6736</fpage>
          <issue-id pub-id-type="doi">10.1136/bmjquality.u209049.w6736</issue-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6. Carter AJE. ST-segment Elevation Myocardial Infarction (STEMI) Bypass: The Importance of Paramedics in an Integrated STEMI System of Care. CJEM. 2018;20(6):813-5. doi: 10.1017/cem.2018.467. PMID: 30484423.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Carter</surname>
              <given-names>AJE</given-names>
            </name>
          </person-group>
          <article-title>ST-segment Elevation Myocardial Infarction (STEMI) Bypass: The Importance of Paramedics in an Integrated STEMI System of Care</article-title>
          <source>CJEM</source>
          <year>2018</year>
          <volume>20</volume>
          <issue>6</issue>
          <fpage>813</fpage>
          <lpage>815</lpage>
          <issue-id pub-id-type="doi">10.1017/cem.2018.467</issue-id>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7. Ribeiro ALP. The Two Brazils and the Treatment of Acute Myocardial Infarction. Arq Bras Cardiol. 2009;93(2):83-4. doi: 10.1590/s0066-782x2009000800003. PMID: 19838482.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ribeiro</surname>
              <given-names>ALP</given-names>
            </name>
          </person-group>
          <article-title>The Two Brazils and the Treatment of Acute Myocardial Infarction</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2009</year>
          <volume>93</volume>
          <issue>2</issue>
          <fpage>83</fpage>
          <lpage>84</lpage>
          <issue-id pub-id-type="doi">10.1590/s0066-782x2009000800003</issue-id>
          <comment>PMID: 19838482</comment>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8. Nascimento BR, Brant LCC, Marino BCA, Passaglia LG, Ribeiro ALP. Implementing Myocardial Infarction Systems of Care in Low/middle-income Countries. Heart. 2019;105(1):20-6. doi: 10.1136/heartjnl-2018-313398.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Marino</surname>
              <given-names>BCA</given-names>
            </name>
            <name>
              <surname>Passaglia</surname>
              <given-names>LG</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>ALP</given-names>
            </name>
          </person-group>
          <article-title>Implementing Myocardial Infarction Systems of Care in Low/middle-income Countries</article-title>
          <source>Heart</source>
          <year>2019</year>
          <volume>105</volume>
          <issue>1</issue>
          <fpage>20</fpage>
          <lpage>26</lpage>
          <issue-id pub-id-type="doi">10.1136/heartjnl-2018-313398</issue-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9. Brasil. Minist&#233;rio da Sa&#250;de. DATASUS &#8211; Tabnet [Internet]. Bras&#237;lia (DF): Minist&#233;rio da Sa&#250;de; 2018 [cited 2022 Jun 6]. Available from: Available from: <ext-link ext-link-type="uri" xlink:href="https://datasus.saude.gov.br/informacoes-de-saude-tabnet/">https://datasus.saude.gov.br/informacoes-de-saude-tabnet/</ext-link> .</mixed-citation>
        <element-citation publication-type="report">
          <person-group person-group-type="author">
            <collab>Brasil</collab>
            <collab>Minist&#233;rio da Sa&#250;de</collab>
          </person-group>
          <source>DATASUS &#8211; Tabnet</source>
          <comment>Internet</comment>
          <publisher-loc>Bras&#237;lia (DF)</publisher-loc>
          <publisher-name>Minist&#233;rio da Sa&#250;de</publisher-name>
          <year>2018</year>
          <date-in-citation content-type="cited-date">cited 2022 Jun 6</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://datasus.saude.gov.br/informacoes-de-saude-tabnet/">https://datasus.saude.gov.br/informacoes-de-saude-tabnet/</ext-link>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10. Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of Studies Conducted using Observational Routinely-collected Health Data (RECORD) Statement. PLoS Med. 2015;12(10):e1001885. doi: 10.1371/journal.pmed.1001885.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Benchimol</surname>
              <given-names>EI</given-names>
            </name>
            <name>
              <surname>Smeeth</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Guttmann</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Harron</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Moher</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Petersen</surname>
              <given-names>I</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>The REporting of Studies Conducted using Observational Routinely-collected Health Data (RECORD) Statement</article-title>
          <source>PLoS Med</source>
          <year>2015</year>
          <volume>12</volume>
          <issue>10</issue>
          <fpage>e1001885</fpage>
          <issue-id pub-id-type="doi">10.1371/journal.pmed.1001885</issue-id>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11. Funda&#231;&#227;o Jo&#227;o Pinheiro. Atlas do Desenvolvimento Humano do Brasil [Internet]. Belo Horizonte: Funda&#231;&#227;o Jo&#227;o Pinheiro; 2022 [cited 2022 Jun 6]. Available from: <ext-link ext-link-type="uri" xlink:href="http://www.atlasbrasil.org.br/">http://www.atlasbrasil.org.br/</ext-link> .</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Funda&#231;&#227;o Jo&#227;o Pinheiro</collab>
          </person-group>
          <source>Atlas do Desenvolvimento Humano do Brasil</source>
          <comment>Internet</comment>
          <publisher-loc>Belo Horizonte</publisher-loc>
          <publisher-name>Funda&#231;&#227;o Jo&#227;o Pinheiro</publisher-name>
          <year>2022</year>
          <date-in-citation content-type="cited-date">cited 2022 Jun 6</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="http://www.atlasbrasil.org.br/">http://www.atlasbrasil.org.br/</ext-link>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12. Marcolino MS, Palhares DM, Benjamin EJ, Ribeiro AL. Atrial Fibrillation: Prevalence in a Large Database of Primary Care Patients in Brazil. Europace. 2015;17(12):1787-90. doi: 10.1093/europace/euv185.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marcolino</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Palhares</surname>
              <given-names>DM</given-names>
            </name>
            <name>
              <surname>Benjamin</surname>
              <given-names>EJ</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <article-title>Atrial Fibrillation: Prevalence in a Large Database of Primary Care Patients in Brazil</article-title>
          <source>Europace</source>
          <year>2015</year>
          <volume>17</volume>
          <issue>12</issue>
          <fpage>1787</fpage>
          <lpage>1790</lpage>
          <issue-id pub-id-type="doi">10.1093/europace/euv185</issue-id>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13. Instituto Brasileiro de Geografia Estat&#237;stica. Panorama da Popula&#231;&#227;o Brasileira [Internet]. Rio de Janeiro: Instituto Brasileiro de Geografia Estat&#237;stica; 2018 [cited 2022 Jun 6]. Available from: <ext-link ext-link-type="uri" xlink:href="https://cidades.ibge.gov.br/brasil/panorama">https://cidades.ibge.gov.br/brasil/panorama</ext-link> .</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Instituto Brasileiro de Geografia Estat&#237;stica</collab>
          </person-group>
          <source>Panorama da Popula&#231;&#227;o Brasileira</source>
          <comment>Internet</comment>
          <publisher-loc>Rio de Janeiro</publisher-loc>
          <publisher-name>Instituto Brasileiro de Geografia Estat&#237;stica</publisher-name>
          <year>2018</year>
          <date-in-citation content-type="cited-date">cited 2022 Jun 6</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://cidades.ibge.gov.br/brasil/panorama">https://cidades.ibge.gov.br/brasil/panorama</ext-link>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14. Brasil. Minist&#233;rio da Sa&#250;de. DATASUS [Internet]. Bras&#237;lia (DF): Minist&#233;rio da Sa&#250;de; 2018 [cited 2022 Jun 6]. Available from: <ext-link ext-link-type="uri" xlink:href="https://datasus.saude.gov.br/">https://datasus.saude.gov.br/</ext-link> .</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Brasil</collab>
            <collab>Minist&#233;rio da Sa&#250;de</collab>
          </person-group>
          <source>DATASUS</source>
          <comment>Internet</comment>
          <publisher-loc>Bras&#237;lia (DF)</publisher-loc>
          <publisher-name>Minist&#233;rio da Sa&#250;de</publisher-name>
          <year>2018</year>
          <date-in-citation content-type="cited-date">cited 2022 Jun 6</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://datasus.saude.gov.br/">https://datasus.saude.gov.br/</ext-link>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15. The R Project for Statistical Computing. A Language and Environment for Statistical Computing. [Internet]. Auckland: R-Project; 2022 [cited 2022 Jun 6]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.r-project.org/">https://www.r-project.org/</ext-link> .</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>The R Project for Statistical Computing</collab>
          </person-group>
          <source>A Language and Environment for Statistical Computing</source>
          <comment>Internet</comment>
          <publisher-loc>Auckland</publisher-loc>
          <publisher-name>R-Project</publisher-name>
          <year>2022</year>
          <date-in-citation content-type="cited-date">cited 2022 Jun 6</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://www.r-project.org/">https://www.r-project.org/</ext-link>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16. Marshall RJ. Mapping Disease and Mortality Rates Using Empirical Bayes Estimators. J R Stat Soc Ser C Appl Stat. 1991;40(2):283-94.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marshall</surname>
              <given-names>RJ</given-names>
            </name>
          </person-group>
          <article-title>Mapping Disease and Mortality Rates Using Empirical Bayes Estimators</article-title>
          <source>J R Stat Soc Ser C Appl Stat</source>
          <year>1991</year>
          <volume>40</volume>
          <issue>2</issue>
          <fpage>283</fpage>
          <lpage>294</lpage>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17. Russo J, Le May MR. Time to Treatment: Focus on Transfer in ST-Elevation Myocardial Infarction. Interv Cardiol Clin. 2016;5(4):427-37. doi: 10.1016/j.iccl.2016.06.003.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Russo</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Le May</surname>
              <given-names>MR</given-names>
            </name>
          </person-group>
          <article-title>Time to Treatment: Focus on Transfer in ST-Elevation Myocardial Infarction</article-title>
          <source>Interv Cardiol Clin</source>
          <year>2016</year>
          <volume>5</volume>
          <issue>4</issue>
          <fpage>427</fpage>
          <lpage>437</lpage>
          <issue-id pub-id-type="doi">10.1016/j.iccl.2016.06.003</issue-id>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18. Frampton J, Devries JT, Welch TD, Gersh BJ. Modern Management of ST-Segment Elevation Myocardial Infarction. Curr Probl Cardiol. 2020;45(3):100393. doi: 10.1016/j.cpcardiol.2018.08.005.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Frampton</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Devries</surname>
              <given-names>JT</given-names>
            </name>
            <name>
              <surname>Welch</surname>
              <given-names>TD</given-names>
            </name>
            <name>
              <surname>Gersh</surname>
              <given-names>BJ</given-names>
            </name>
          </person-group>
          <article-title>Modern Management of ST-Segment Elevation Myocardial Infarction</article-title>
          <source>Curr Probl Cardiol</source>
          <year>2020</year>
          <volume>45</volume>
          <issue>3</issue>
          <fpage>100393</fpage>
          <issue-id pub-id-type="doi">10.1016/j.cpcardiol.2018.08.005</issue-id>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19. Bordon JG, Paiva SA, Matsubara LS, Inoue RM, Matsui M, Gut AL, et al. Mortality Decline After Implementation of Standard Protocols for Treating Patients with Acute Myocardial Infarction. Arq Bras Cardiol. 2004;82(4):370-7. doi: 10.1590/s0066-782x2004000400008.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bordon</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Paiva</surname>
              <given-names>SA</given-names>
            </name>
            <name>
              <surname>Matsubara</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Inoue</surname>
              <given-names>RM</given-names>
            </name>
            <name>
              <surname>Matsui</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Gut</surname>
              <given-names>AL</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Mortality Decline After Implementation of Standard Protocols for Treating Patients with Acute Myocardial Infarction</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2004</year>
          <volume>82</volume>
          <issue>4</issue>
          <fpage>370</fpage>
          <lpage>377</lpage>
          <issue-id pub-id-type="doi">10.1590/s0066-782x2004000400008</issue-id>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20. Jollis JG, Mehta RH, Roettig ML, Berger PB, Babb JD, Granger CB. Reperfusion of acute myocardial infarction in North Carolina emergency departments (RACE): Study Design. Am Heart J. 2006;152(5):851.e1-11. doi: 10.1016/j.ahj.2006.06.036.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Jollis</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Mehta</surname>
              <given-names>RH</given-names>
            </name>
            <name>
              <surname>Roettig</surname>
              <given-names>ML</given-names>
            </name>
            <name>
              <surname>Berger</surname>
              <given-names>PB</given-names>
            </name>
            <name>
              <surname>Babb</surname>
              <given-names>JD</given-names>
            </name>
            <name>
              <surname>Granger</surname>
              <given-names>CB</given-names>
            </name>
          </person-group>
          <article-title>Reperfusion of acute myocardial infarction in North Carolina emergency departments (RACE): Study Design</article-title>
          <source>Am Heart J</source>
          <year>2006</year>
          <volume>152</volume>
          <issue>5</issue>
          <fpage>851.e1</fpage>
          <lpage>851.11</lpage>
          <issue-id pub-id-type="doi">10.1016/j.ahj.2006.06.036</issue-id>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21. Lana MLL, Beaton AZ, Brant LCC, Bozzi ICRS, Magalh&#227;es O, Castro LRA, et al. Factors Associated with Compliance to AHA/ACC Performance Measures in a Myocardial Infarction System of Care in Brazil. Int J Qual Health Care. 2017;29(4):499-506. doi: 10.1093/intqhc/mzx059. PMID: 28531328.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lana</surname>
              <given-names>MLL</given-names>
            </name>
            <name>
              <surname>Beaton</surname>
              <given-names>AZ</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Bozzi</surname>
              <given-names>ICRS</given-names>
            </name>
            <name>
              <surname>Magalh&#227;es</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Castro</surname>
              <given-names>LRA</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Factors Associated with Compliance to AHA/ACC Performance Measures in a Myocardial Infarction System of Care in Brazil</article-title>
          <source>Int J Qual Health Care</source>
          <year>2017</year>
          <volume>29</volume>
          <issue>4</issue>
          <fpage>499</fpage>
          <lpage>506</lpage>
          <issue-id pub-id-type="doi">10.1093/intqhc/mzx059</issue-id>
          <comment>PMID: 28531328</comment>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>22. Marcolino MS, Brant LC, Araujo JG, Nascimento BR, Castro LR, Martins P, et al. Implementation of the Myocardial Infarction System of Care in City of Belo Horizonte, Brazil. Arq Bras Cardiol. 2013;100(4):307-14.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marcolino</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LC</given-names>
            </name>
            <name>
              <surname>Araujo</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Castro</surname>
              <given-names>LR</given-names>
            </name>
            <name>
              <surname>Martins</surname>
              <given-names>P</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Implementation of the Myocardial Infarction System of Care in City of Belo Horizonte, Brazil</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2013</year>
          <volume>100</volume>
          <issue>4</issue>
          <fpage>307</fpage>
          <lpage>314</lpage>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>23. Marino BCA, Ribeiro ALP, Alkmim MBM, Antunes AP, Boersma E, Marcolino MS. Coordinated Regional Care of Myocardial Infarction in a Rural Area in Brazil &#8211; Minas Telecardio Project 2. European Heart Journal &#8211; Quality of Care and Clinical Outcomes. doi: 10.1093/ehjqcco/qcw020.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marino</surname>
              <given-names>BCA</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>ALP</given-names>
            </name>
            <name>
              <surname>Alkmim</surname>
              <given-names>MBM</given-names>
            </name>
            <name>
              <surname>Antunes</surname>
              <given-names>AP</given-names>
            </name>
            <name>
              <surname>Boersma</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Marcolino</surname>
              <given-names>MS</given-names>
            </name>
          </person-group>
          <article-title>Coordinated Regional Care of Myocardial Infarction in a Rural Area in Brazil &#8211; Minas Telecardio Project 2</article-title>
          <source>European Heart Journal &#8211; Quality of Care and Clinical Outcomes</source>
          <issue-id pub-id-type="doi">10.1093/ehjqcco/qcw020</issue-id>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>24. Lodi-Junqueira L, Ribeiro AL. Tackling Acute Coronary Syndrome in Low-income and middle-income Countries. Heart. 2018;104(17):1390-1. doi: 10.1136/heartjnl-2018-313013.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lodi-Junqueira</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <article-title>Tackling Acute Coronary Syndrome in Low-income and middle-income Countries</article-title>
          <source>Heart</source>
          <year>2018</year>
          <volume>104</volume>
          <issue>17</issue>
          <fpage>1390</fpage>
          <lpage>1391</lpage>
          <issue-id pub-id-type="doi">10.1136/heartjnl-2018-313013</issue-id>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25. World Health Organization. World Health Statistics 2017: Monitoring Health for the SDGs, Sustainable Development Goals [Internet]. Geneva: World Health Organization; 2017 [cited 2022 Jun 6]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3480">https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3480</ext-link> .</mixed-citation>
        <element-citation publication-type="report">
          <person-group person-group-type="author">
            <collab>World Health Organization</collab>
          </person-group>
          <source>World Health Statistics 2017: Monitoring Health for the SDGs, Sustainable Development Goals</source>
          <comment>Internet</comment>
          <publisher-loc>Geneva</publisher-loc>
          <publisher-name>World Health Organization</publisher-name>
          <year>2017</year>
          <date-in-citation content-type="cited-date">cited 2022 Jun 6</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3480">https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3480</ext-link>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>26. Nascimento BR, Brant LCC, Marino BCA, Passaglia LG, Ribeiro ALP. Implementing Myocardial Infarction Systems of Care in Low/middle-income Countries. Heart. 2019;105(1):20-6. doi: 10.1136/heartjnl-2018-313398.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Marino</surname>
              <given-names>BCA</given-names>
            </name>
            <name>
              <surname>Passaglia</surname>
              <given-names>LG</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>ALP</given-names>
            </name>
          </person-group>
          <article-title>Implementing Myocardial Infarction Systems of Care in Low/middle-income Countries</article-title>
          <source>Heart</source>
          <year>2019</year>
          <volume>105</volume>
          <issue>1</issue>
          <fpage>20</fpage>
          <lpage>26</lpage>
          <issue-id pub-id-type="doi">10.1136/heartjnl-2018-313398</issue-id>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>27. Keatinge WR, Coleshaw SR, Cotter F, Mattock M, Murphy M, Chelliah R. Increases in Platelet and Red Cell Counts, Blood Viscosity, and Arterial Pressure during Mild Surface Cooling: Factors in Mortality from Coronary and Cerebral Thrombosis in Winter. Br Med J (Clin Res Ed). 1984;289(6456):1405-8. doi: 10.1136/bmj.289.6456.1405.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Keatinge</surname>
              <given-names>WR</given-names>
            </name>
            <name>
              <surname>Coleshaw</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Cotter</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Mattock</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Murphy</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Chelliah</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Increases in Platelet and Red Cell Counts, Blood Viscosity, and Arterial Pressure during Mild Surface Cooling: Factors in Mortality from Coronary and Cerebral Thrombosis in Winter</article-title>
          <source>Br Med J (Clin Res Ed)</source>
          <year>1984</year>
          <volume>289</volume>
          <issue>6456</issue>
          <fpage>1405</fpage>
          <lpage>1408</lpage>
          <pub-id pub-id-type="doi">10.1136/bmj.289.6456.1405</pub-id>
        </element-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <mixed-citation>28. Corrales-Medina VF, Suh KN, Rose G, Chirinos JA, Doucette S, Cameron DW, et al. Cardiac Complications in Patients with Community-acquired Pneumonia: A Systematic Review and Meta-analysis of Observational Studies. PLoS Med. 2011;8(6):e1001048. doi: 10.1371/journal.pmed.1001048.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Corrales-Medina</surname>
              <given-names>VF</given-names>
            </name>
            <name>
              <surname>Suh</surname>
              <given-names>KN</given-names>
            </name>
            <name>
              <surname>Rose</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Chirinos</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Doucette</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Cameron</surname>
              <given-names>DW</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Cardiac Complications in Patients with Community-acquired Pneumonia: A Systematic Review and Meta-analysis of Observational Studies</article-title>
          <source>PLoS Med</source>
          <year>2011</year>
          <volume>8</volume>
          <issue>6</issue>
          <fpage>e1001048</fpage>
          <issue-id pub-id-type="doi">10.1371/journal.pmed.1001048</issue-id>
        </element-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <mixed-citation>29. Corrales-Medina VF, Madjid M, Musher DM. Role of Acute Infection in Triggering Acute Coronary Syndromes. Lancet Infect Dis. 2010;10(2):83-92. doi: 10.1016/S1473-3099(09)70331-7.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Corrales-Medina</surname>
              <given-names>VF</given-names>
            </name>
            <name>
              <surname>Madjid</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Musher</surname>
              <given-names>DM</given-names>
            </name>
          </person-group>
          <article-title>Role of Acute Infection in Triggering Acute Coronary Syndromes</article-title>
          <source>Lancet Infect Dis</source>
          <year>2010</year>
          <volume>10</volume>
          <issue>2</issue>
          <fpage>83</fpage>
          <lpage>92</lpage>
          <issue-id pub-id-type="doi">10.1016/S1473-3099(09)70331-7</issue-id>
        </element-citation>
      </ref>
      <ref id="B30">
        <label>30</label>
        <mixed-citation>30. Warren-Gash C, Blackburn R, Whitaker H, McMenamin J, Hayward AC. Laboratory-confirmed Respiratory Infections as Triggers for Acute Myocardial Infarction and Stroke: a Self-controlled Case Series Analysis of National Linked Datasets from Scotland. Eur Respir J. 2018;51(3):1701794. doi: 10.1183/13993003.01794-2017.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Warren-Gash</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Blackburn</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Whitaker</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>McMenamin</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Hayward</surname>
              <given-names>AC</given-names>
            </name>
          </person-group>
          <article-title>Laboratory-confirmed Respiratory Infections as Triggers for Acute Myocardial Infarction and Stroke: a Self-controlled Case Series Analysis of National Linked Datasets from Scotland</article-title>
          <source>Eur Respir J</source>
          <year>2018</year>
          <volume>51</volume>
          <issue>3</issue>
          <fpage>1701794</fpage>
          <issue-id pub-id-type="doi">10.1183/13993003.01794-2017</issue-id>
        </element-citation>
      </ref>
      <ref id="B31">
        <label>31</label>
        <mixed-citation>31. Marra F, Zhang A, Gillman E, Bessai K, Parhar K, Vadlamudi NK. The Protective Effect of Pneumococcal Vaccination on Cardiovascular Disease in Adults: A Systematic Review and Meta-analysis. Int J Infect Dis. 2020;99:204-13. doi: 10.1016/j.ijid.2020.07.038.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marra</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Zhang</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Gillman</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Bessai</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Parhar</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Vadlamudi</surname>
              <given-names>NK</given-names>
            </name>
          </person-group>
          <article-title>The Protective Effect of Pneumococcal Vaccination on Cardiovascular Disease in Adults: A Systematic Review and Meta-analysis</article-title>
          <source>Int J Infect Dis</source>
          <year>2020</year>
          <volume>99</volume>
          <fpage>204</fpage>
          <lpage>213</lpage>
          <issue-id pub-id-type="doi">10.1016/j.ijid.2020.07.038</issue-id>
        </element-citation>
      </ref>
      <ref id="B32">
        <label>32</label>
        <mixed-citation>32. Hospital Israelita Albert Einstein, Ministry of Health. Vaccination Against Influenza to Prevent Cardiovascular Events After Acute Coronary Syndromes (VIP-ACS) [Internet]. US National Library of Medicine; 2021 [cited 2022 Jun 6]. Available from: <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04001504">https://clinicaltrials.gov/ct2/show/NCT04001504</ext-link> .</mixed-citation>
        <element-citation publication-type="report">
          <person-group person-group-type="author">
            <collab>Hospital Israelita Albert Einstein</collab>
            <collab>Ministry of Health</collab>
          </person-group>
          <source>Vaccination Against Influenza to Prevent Cardiovascular Events After Acute Coronary Syndromes (VIP-ACS)</source>
          <comment>Internet</comment>
          <publisher-name>US National Library of Medicine</publisher-name>
          <year>2021</year>
          <date-in-citation content-type="cited-date">cited 2022 Jun 6</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04001504">https://clinicaltrials.gov/ct2/show/NCT04001504</ext-link>
        </element-citation>
      </ref>
      <ref id="B33">
        <label>33</label>
        <mixed-citation>33. Hayes RB, Lim C, Zhang Y, Cromar K, Shao Y, Reynolds HR, et al. PM2.5 Air Pollution and Cause-specific Cardiovascular Disease Mortality. Int J Epidemiol. 2020;49(1):25-35. doi: 10.1093/ije/dyz114.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Hayes</surname>
              <given-names>RB</given-names>
            </name>
            <name>
              <surname>Lim</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Zhang</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Cromar</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Shao</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Reynolds</surname>
              <given-names>HR</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>PM2.5 Air Pollution and Cause-specific Cardiovascular Disease Mortality</article-title>
          <source>Int J Epidemiol</source>
          <year>2020</year>
          <volume>49</volume>
          <issue>1</issue>
          <fpage>25</fpage>
          <lpage>35</lpage>
          <issue-id pub-id-type="doi">10.1093/ije/dyz114</issue-id>
        </element-citation>
      </ref>
      <ref id="B34">
        <label>34</label>
        <mixed-citation>34. Lelieveld J, Evans JS, Fnais M, Giannadaki D, Pozzer A. The Contribution of Outdoor Air Pollution Sources to Premature Mortality on a Global Scale. Nature. 2015;525(7569):367-71. doi: 10.1038/nature15371.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Lelieveld</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Evans</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Fnais</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Giannadaki</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Pozzer</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
          <article-title>The Contribution of Outdoor Air Pollution Sources to Premature Mortality on a Global Scale</article-title>
          <source>Nature</source>
          <year>2015</year>
          <volume>525</volume>
          <issue>7569</issue>
          <fpage>367</fpage>
          <lpage>371</lpage>
          <issue-id pub-id-type="doi">10.1038/nature15371</issue-id>
        </element-citation>
      </ref>
      <ref id="B35">
        <label>35</label>
        <mixed-citation>35. Sunyer J, Ballester F, Tertre AL, Atkinson R, Ayres JG, Forastiere F, et al. The Association of Daily Sulfur Dioxide Air Pollution Levels with Hospital Admissions for Cardiovascular Diseases in Europe (The Aphea-II study). Eur Heart J. 2003;24(8):752-60. doi: 10.1016/s0195-668x(02)00808-4.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Sunyer</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Ballester</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Tertre</surname>
              <given-names>AL</given-names>
            </name>
            <name>
              <surname>Atkinson</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Ayres</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Forastiere</surname>
              <given-names>F</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>The Association of Daily Sulfur Dioxide Air Pollution Levels with Hospital Admissions for Cardiovascular Diseases in Europe (The Aphea-II study)</article-title>
          <source>Eur Heart J</source>
          <year>2003</year>
          <volume>24</volume>
          <issue>8</issue>
          <fpage>752</fpage>
          <lpage>760</lpage>
          <issue-id pub-id-type="doi">10.1016/s0195-668x(02)00808-4</issue-id>
        </element-citation>
      </ref>
    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <p>Vincula&#231;&#227;o acad&#234;mica</p>
        <p>Este artigo &#233; parte de tese de Mestrado de Rodrigo Costa Pereira Vieira pela Universidade Federal de Minas Gerais.</p>
      </fn>
      <fn fn-type="other">
        <p>Aprova&#231;&#227;o &#233;tica e consentimento informado</p>
        <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
      </fn>
    </fn-group>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>Fontes de financiamento: O presente estudo foi financiado por CNPq (310790/2021-2), FAPEMIG (PPM-00428-17 e RED-00081-16) e IATS/CNPq [n&#250;mero 147122/2021-0].</p>
      </fn>
    </fn-group>
    <app-group>
      <app id="app1">
        <title>* Material suplementar</title>
        <p>Para informa&#231;&#227;o adicional, por favor, <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11905/2021-0953-supplemental.pdf">clique aqui</ext-link>.</p>
      </app>
    </app-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Assessment of the Impact of the Implementation of a Pre-Hospital Ambulance System on Acute Myocardial Infarction Mortality in a Developing Country</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Vieira</surname>
            <given-names>Rodrigo Costa Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4278-3771</contrib-id>
          <name>
            <surname>Marcolino</surname>
            <given-names>Milena Soriano</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-8297-8704</contrib-id>
          <name>
            <surname>Silva</surname>
            <given-names>Luis Gustavo Silva e</given-names>
          </name>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-3124-9322</contrib-id>
          <name>
            <surname>Pereira</surname>
            <given-names>Daniella Nunes</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5586-774X</contrib-id>
          <name>
            <surname>Nascimento</surname>
            <given-names>Bruno Ramos</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1366-1732</contrib-id>
          <name>
            <surname>Jorge</surname>
            <given-names>Alzira de Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2740-0042</contrib-id>
          <name>
            <surname>Ribeiro</surname>
            <given-names>Antonio Luiz P</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade de Medicina e Hospital Universit&#225;rio, Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brazil</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Rede de Telessa&#250;de de Minas Gerais, Belo Horizonte, MG &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Antonio Luiz P Ribeiro &#8226; Universidade Federal de Minas Gerais - Avenida Professor Alfredo Balena, 110, 1&#186; Andar, Ala Sul, Sala 107. Postal Code 30130-100, Belo Horizonte, MG - Brazil E-mail: tom1963br@yahoo.com.br, tom@hc.ufmg.br</corresp>
        <fn id="fn1001">
          <p>Author Contributions</p>
          <p>Conception and design of the research: Vieira RCP, Marcolino MS, Nascimento BR, Ribeiro ALP; Acquisition of data and Statistical analysis: Vieira RCP, Marcolino MS, Silva LGS; Analysis and interpretation of the data: Vieira RCP, Marcolino MS, Silva LGS, Ribeiro ALP; Obtaining financing: Vieira RCP, Marcolino MS, Ribeiro ALP; Writing of the manuscript: Vieira RCP, Marcolino MS, Pereira DN, Jorge AO, Ribeiro ALP; Critical revision of the manuscript for important intellectual content: Vieira RCP, Marcolino MS, Silva LGS, Pereira DN, Nascimento BR, Jorge AO, Ribeiro ALP.</p>
        </fn>
        <fn>
          <p>Potential Conflict of Interest</p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background</title>
          <p>The effective management of patients with acute myocardial infarction (AMI) is time-dependent.</p>
        </sec>
        <sec>
          <title>Objectives</title>
          <p>To assess the impacts of the implementation of prehospital care on admission rates and mortality associated with AMI.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p>Retrospective, ecological study, which assessed data from the Brazilian Universal Health System, from all 853 municipalities of Minas Gerais, from 2008 to 2016. Excessive skewness of general and in-hospital mortality rates was smoothed using the empirical Bayes method. This study assessed the relationship between Mobile Emergency Care Service (SAMU) in each municipality and the following 3 outcomes: mortality rate due to AMI, AMI in-hospital mortality, and AMI hospitalization rate, using the Poisson hierarchical model. Rates were corrected by age structure and detrended by seasonality and temporal influences. A confidence interval of 95% was adopted.</p>
        </sec>
        <sec>
          <title>Results</title>
          <p>AMI mortality rates decreased throughout the study, on average 2% per year, with seasonal variation. AMI in-hospital mortality also showed a decreasing trend, from 13.81% in 2008 to 11.43% in 2016. SAMU implementation was associated with decreased AMI mortality (odds ratio [OR] = 0.967, 95% confidence interval [CI] 0.936 to 0.998) and AMI in-hospital mortality (OR = 0.914, 95% CI 0.845 to 0.986), with no relation with hospitalizations (OR = 1.003, 95% CI 0.927 to 1.083).</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p>SAMU implementation was associated with a modest but significant decrease in AMI in-hospital mortality. This finding reinforces the key role of prehospital care in AMI care and the need for investments on this service to improve clinical outcomes in low- and middle-income countries.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Acute Myocardial Infarction</kwd>
        <kwd>Emergency Medical Services</kwd>
        <kwd>Hospital Mortality</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup> The effective management of patients with AMI is directly linked to time to medical assistance, and approximately one half of the deaths attributed to AMI result from out-of-hospital cardiac arrest, reinforcing the importance of prehospital care and, ultimately, the development of evidence-based AMI systems of care.</p>
        <p>Specifically, in relation to ST-elevation myocardial infarction, early diagnosis and appropriate reperfusion therapy are of the utmost importance for mortality reduction. Primary percutaneous coronary intervention (PCI), the first choice for reperfusion, when available, is more effective than thrombolytic therapy, but it should ideally be performed up to 120 minutes after the first medical contact, or within 90 minutes if the patient presents at a primary PCI-capable unit. Thrombolysis is more effective when delivered within 3 hours of symptom onset. Either strategy should be delivered no later than 12 hours after symptom onset.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> In clinical practice, a significant proportion of patients do not receive care that meets those time targets, and the situation is even worse in rural communities and under-resourced areas.<sup><xref ref-type="bibr" rid="B3">3</xref> - <xref ref-type="bibr" rid="B7">7</xref></sup></p>
        <p>There is still a lack of contemporary data about the impact of the use of prehospital care in the setting of AMI, especially in low- and middle-income countries, particularly from the more generalizable perspective of a community-based investigation, as well as information about hospital outcomes of patients transported by ambulance. However, it is known that the first minutes after AMI onset are crucial to the patient&#8217;s prognosis and survival, and, considering that, it is important to objectively evaluate the possible impacts of emergency prehospital services on AMI management and outcomes.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Nonetheless, it is difficult to obtain this type of information from observational studies, as there is no control over the classification of the studied variables, and it is often difficult to isolate the dependent variable.</p>
        <p>Therefore, we aimed to assess the impacts of the implementation of a nationwide ambulance service ( <italic>Servi&#231;o de Atendimento M&#233;dico de Urg&#234;ncia</italic> , SAMU) on hospitalization rates and general and AMI in-hospital mortality in the state of Minas Gerais (MG), in the Southeast Region of Brazil.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>This is an observational, retrospective, ecological study, which assessed data from the Brazilian Universal Health System (SUS, DataSUS TabNET),<sup><xref ref-type="bibr" rid="B9">9</xref></sup> from all 853 municipalities of the Brazilian state of MG, from 2008 to 2016. It follows the RECORD statement for studies that use routinely collected health data.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
        <p>MG is the Brazilian state with the largest number of municipalities (853), and it is located in the Southeast Region of Brazil. It is the second most populous state in Brazil, with 21 million inhabitants distributed across an area comparable to France. The average Human Development Index (HDI) is 0.731, and 14.46% of the population is considered poor or very poor, according to the Brazilian Institute of Geography and Statistics (IBGE).<sup><xref ref-type="bibr" rid="B11">11</xref></sup> MG can be considered representative of the country, as age distribution, percentage of urbanization, and social inequality are similar to the overall national pattern. The north and the northeast of MG have the lowest HDI, similar to the North and Northeast regions of Brazil, while the west and south of the state have HDI similar to the areas with the highest HDI in the country.<sup><xref ref-type="bibr" rid="B10">10</xref> - <xref ref-type="bibr" rid="B12">12</xref></sup></p>
        <p>The Brazilian nationwide ambulance service, called SAMU, was implemented in the state of MG in 2003 by a national program called &#8220; <italic>Pol&#237;tica Nacional das Urg&#234;ncias</italic> &#8221; (National Emergency Policy). The program started in some selected municipalities, which were responsible for managing their own system. Since 2009 regionalized prehospital care systems were created, called &#8220;consortiums&#8221;, which currently correspond to the main model of care and cover various regions of the state. In the period analyzed, there were five consortia in the state: Cons&#243;rcio Intermunicipal de Sa&#250;de da Macrorregi&#227;o do Sul de Minas (CISSUL), Cons&#243;rcio Intermunicipal de Sa&#250;de da Regi&#227;o Sudeste (CISDESTE), Cons&#243;rcio Intermunicipal de Sa&#250;de da Rede de Urg&#234;ncia Centro Sul (CISRU), Urg&#234;ncia do Norte de Minas (CISRUN) and Cons&#243;rcio Intermunicipal de Sa&#250;de Rede de Urg&#234;ncia Macro Nordeste/ Jequitinhonha (CISNORJE), covering 469 municipalities in the south, southeast, center-south, north, and northeast regions, respectively ( <xref ref-type="fig" rid="f01001">Figure 1</xref> ).</p>
        <p>
          <fig id="f01001">
            <label>Figure 1</label>
            <caption>
              <title>Distribution of municipal SAMUs and SAMU consortia in Minas Gerais. Acronyms: CISDESTE: Cons&#243;rcio Intermunicipal de Sa&#250;de da Regi&#227;o Sudeste; CISNORJE: Cons&#243;rcio Intermunicipal de Sa&#250;de Rede de Urg&#234;ncia Macro Nordeste/Jequitinhonha; CISRU: Cons&#243;rcio Intermunicipal de Sa&#250;de da Rede de Urg&#234;ncia Centro-Sul; CISRUN: Cons&#243;rcio Intermunicipal de Sa&#250;de da Rede de Urg&#234;ncia do Norte de Minas; CISSUL: Cons&#243;rcio Intermunicipal de Sa&#250;de da Macrorregi&#227;o do Sul de Minas; SAMU: Mobile Emergency Care Service. Source: SES-MH 2016.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf01-en.tif"/></fig>
        </p>
        <p>SAMU implementation dates were obtained from the state government and local SAMU coordinators. The first inter-city consortium was implemented in 2009, one in 2011, two in 2012, and one in 2015. Some services were implemented before the analyzed time period, while others were implemented during the study period. At the same time, some municipalities had already implemented SAMU consortiums at the beginning of the analysis, while others implemented SAMU during the study period and others did not have SAMU within this time frame. Fourteen municipalities had SAMU during the analysis period (municipal SAMUs). SAMU was implemented in 86 municipalities in January 2009 (CISRUN), in 94 municipalities in November 2014 (CISDESTE), in 86 municipalities in April 2012 (CISNORJE), in 51 municipalities in June 2012 (CISRU), and in 152 municipalities in July 2015 (CISSUL). The remaining municipalities of the state (n = 370) remained without SAMU throughout the study period. <inline-supplementary-material mime-subtype="pdf" mimetype="application" xlink:href="">Supplementary Figure 1</inline-supplementary-material> shows the evolution of SAMU coverage in the state, as each regional consortium was implemented.</p>
        <p>The outcomes of interest were AMI general and in-hospital mortality rates and rate of admissions due to AMI, assessed from 2008 to 2016. The choice of those outcomes is justified by the fact that they have the greatest clinical and epidemiological relevance and greatest potential for association with SAMU implementation, in addition to high completion rates, as mandatory variables.</p>
        <p>Data on the population of each municipality was obtained from IBGE, the official demographic and statistical institute of Brazil.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> For deaths and hospitalizations, data were extracted from DATASUS TabNET,<sup><xref ref-type="bibr" rid="B9">9</xref></sup> an electronic database that collects patient-level information from the SUS. We used information of monthly occurrences of those outcomes, from the Mortality Information System (SIM) and the Hospital Information System (SIH) databases, respectively, for the population of the 853 municipalities of MG, from 2008 to 2016.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
        <p>Deaths were considered AMI deaths when the main cause of death had the following ICD-10 codes (I21 to I24): I21 &#8220;acute myocardial infarction&#8221;, I22 &#8220;recurrent myocardial infarction&#8221;, I23 &#8220;some current complications subsequent to acute myocardial infarction&#8221;, I24 &#8220;other acute ischemic heart diseases&#8221;. Data from the SIH was used to obtain data on hospital admissions due to AMI: procedure &#8220;treatment of AMI&#8221;, SIH/DATASUS code 03.03.06.019-0 and &#8220;primary coronary angioplasty&#8221;, code 040.603.004-9. In this study, AMI in-hospital mortality was calculated from the number of deaths with the aforementioned codes, divided by the number of hospitalizations with these same codes in each municipality per month of analysis.</p>
        <p>As the study used public data available through the DATASUS platform, approval by a research ethics committee was not necessary.</p>
        <sec>
          <title>Data analysis</title>
          <p>The software R version 3.3.4 was used for statistical analysis.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> The unit of analysis was the municipality. A monthly analysis of the outcomes, from January 2008 to December 2016, for each of the 853 municipalities in MG was performed, considering the population by estimates of each year.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
          <p>The 3 outcomes were adjusted for the age structure, based on the population of 2010.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> The rates were estimated for each municipality and month considering the adjustment for age. The municipalities were indexed by i = 1, &#8230;, n, where n = 853 is the total number of municipalities, while the months were indexed by t = 1, &#8230;, T, where T is the number of months in the period analyzed.</p>
          <p>Excessive skewness of AMI mortality and in-hospital mortality rates were smoothed using the empirical Bayes method.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> The method was used to estimate the rates instead of the classic rate estimate approach. In the classical approach, the rate is calculated as the ratio of the number of events (deaths, hospitalizations) per the population at risk. Therefore, the variability of the estimated rates is strongly affected by small changes in the number of events (deaths) when they are computed for small areas where the expected value for events is low. The empirical Bayes method aims to minimize the variations of the estimated rates through a weighted average between the municipal rate and the regional rate. In the present study, the region was defined as the state of MG. The weights were interpreted by the population size; the higher a population was, the lesser the weight of the region rate. The AMI mortality and hospitalization rates were modeled using Poisson distribution, while AMI in-hospital mortality was using binomial distribution, and then estimated them through the empirical Bayes method (<inline-supplementary-material mime-subtype="pdf" mimetype="application" xlink:href="">Supplementary Figures 2</inline-supplementary-material> and <inline-supplementary-material mime-subtype="pdf" mimetype="application" xlink:href="">3</inline-supplementary-material>). Hospital admissions with the aforementioned SIH/DATASUS hospital admission codes from 2008 to 2016 in all municipalities of MG were assessed and, as this variable is also subject to significant variations in municipalities with small populations, the global empirical Bayes method was used for adjustment, as explained for mortality rate analysis.</p>
          <p>Seasonality and temporal trends of decrease in the general and hospital mortality rates were observed, with semiannual tendency in the oscillation between the lowest and highest rates and gradual reduction of the same over the analyzed period. Thus, seasonality and temporality were included in the statistical analysis models. This study assessed the relationship between the availability of SAMU care in each municipality and the following 3 outcomes: the mortality due to AMI in the general population, AMI in-hospital mortality, and number of hospitalizations due to AMI, using the Poisson hierarchical model, and the analyzed rates were corrected by the age structure and detrended by temporal and seasonal influences. A 95% confidence interval (CI) was used for all outcomes.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>AMI mortality rates, adjusted by age distribution, showed a decreasing trend throughout the study, ranging from 35.7 deaths per 100,000 inhabitants in 2008 to 30.4 deaths per 100,000 inhabitants in 2016, i.e., about 2% per year on average ( <xref ref-type="table" rid="t1001">Table 1</xref> ). Seasonal variation in AMI mortality rates was also observed, and it was higher during the winter season and lower during the summer season ( <xref ref-type="fig" rid="f02001">Figure 2</xref> ).</p>
        <p>
          <table-wrap id="t1001">
            <label>Table 1</label>
            <caption>
              <title>Annual AMI mortality, hospitalization, and in-hospital mortality rates, adjusted by age, in the state of Minas Gerais from 2008 to 2016</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Year</th>
                  <th>Mortality (per 100,000)</th>
                  <th>In-hospital mortality (%)*</th>
                  <th>Hospitalization (per 100,000)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>2008</td>
                  <td align="center">35.7 (35.3 &#8211; 36.1)</td>
                  <td align="center">13.81</td>
                  <td align="center">152 (146 - 158)</td>
                </tr>
                <tr>
                  <td>2009</td>
                  <td align="center">34.1 (33.8 &#8211; 34.5)</td>
                  <td align="center">13.65</td>
                  <td align="center">150 (144 - 156)</td>
                </tr>
                <tr>
                  <td>2010</td>
                  <td align="center">35.0 (34.6 &#8211; 35.3)</td>
                  <td align="center">13.78</td>
                  <td align="center">140 (134 - 145)</td>
                </tr>
                <tr>
                  <td>2011</td>
                  <td align="center">33.8 (33.4 &#8211; 34.1)</td>
                  <td align="center">11.82</td>
                  <td align="center">147 (142 - 152)</td>
                </tr>
                <tr>
                  <td>2012</td>
                  <td align="center">32.4 (32.1 &#8211; 32.6)</td>
                  <td align="center">11.29</td>
                  <td align="center">146 (141 - 151)</td>
                </tr>
                <tr>
                  <td>2013</td>
                  <td align="center">31.9 (31.7 &#8211; 32.2)</td>
                  <td align="center">11.99</td>
                  <td align="center">142 (137 - 146)</td>
                </tr>
                <tr>
                  <td>2014</td>
                  <td align="center">30.9 (30.6 &#8211; 31.1)</td>
                  <td align="center">12.15</td>
                  <td align="center">137 (132 - 141)</td>
                </tr>
                <tr>
                  <td>2015</td>
                  <td align="center">29.9 (29.7 &#8211; 30.2)</td>
                  <td align="center">10.82</td>
                  <td align="center">138 (133 - 142)</td>
                </tr>
                <tr>
                  <td>2016</td>
                  <td align="center">30.4 (30.1 &#8211; 30.6)</td>
                  <td align="center">11.43</td>
                  <td align="center">147 (142 - 151)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1001">
                <p>
                  <italic>*Rates are expressed with 95% confidence</italic>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>
          <fig id="f02001">
            <label>Figure 2</label>
            <caption>
              <title>Occurrence of seasonal variation in mortality rates from 2008 to 2016. A higher mortality rate is observed during winter, and lower rates are observed during summer.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf02-en.tif"/></fig>
        </p>
        <p>Age-corrected AMI in-hospital mortality also showed a decreasing trend, from 13.81% in 2008 to 11.43% in 2016 ( <xref ref-type="table" rid="t1001">Table 1</xref> ), with wide monthly variations and a seasonal pattern, although this was less evident when compared to AMI mortality rate ( <xref ref-type="fig" rid="f03001">Figure 3</xref> ).</p>
        <p>
          <fig id="f03001">
            <label>Figure 3</label>
            <caption>
              <title>Lethality and mortality monthly rates for the municipalities of Minas Gerais, from 2008 to 2016. Green dots represent monthly lethality rates for the whole analyzed population, which presents considerable monthly variation with no defined seasonal pattern. The red line represents the rate trend through time, with an accentuated reduction from 2008 to 2012, stagnation at 2013 and a new slower decrease from 2014 to 2016. We observed that the implementation of Mobile Emergency Care Service (SAMU), represented by the vertical blue lines, did not have any clear influence on lethality on the descriptive analysis.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf03-en.tif"/></fig>
        </p>
        <p>SAMU implementation was associated with decreased AMI mortality (odds ratio [OR] = 0.967, 95% CI 0.936 to 0.998) and AMI in-hospital mortality (OR = 0.914, 95% CI 0.845 to 0.986) with no significant association with the number of hospitalizations (OR 1.003, 95% CI 0.927 to 1.083). There was no seasonal variation in the number of AMI hospitalizations during the study period.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>In the present study, it was observed that the implementation of SAMU in the Brazilian state of MG was associated with a reduction in general AMI mortality rates. Age-corrected AMI in-hospital mortality also showed a decreasing trend over time, with a seasonal pattern. However, no significant association was found with AMI hospitalization rates during the analyzed period.</p>
        <p>Despite the lack of evidence in developing countries, these results are in line with studies developed in high-income countries, and they are likely related to increased patient access to some type of AMI treatment and decreased time between symptom onset and initiation of specific therapy, including reperfusion when indicated.<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B17">17</xref> , <xref ref-type="bibr" rid="B18">18</xref></sup> On the other hand, some studies have failed to demonstrate an association between the implementation of AMI systems of care and decreased mortality, despite the improvement in quality of healthcare, adherence to guideline-driven recommendations, and shortened treatment times.<sup><xref ref-type="bibr" rid="B3">3</xref> - <xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B12">12</xref> , <xref ref-type="bibr" rid="B19">19</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup> This has occurred even with the use of protocols designed with multiple interventions other than prehospital care only. Among these studies, the Reperfusion of Acute myocardial infarction in North Carolina Emergency departments (RACE) stands out. It was conducted in the state of North Carolina, USA, leading to a reduction in consultation time and the delays for reperfusion treatment administration following the implementation and systematization of protocols for AMI patient care.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
        <p>Differently from previous reports, our study was conducted in a middle-income country, a fact that can help to explain our positive results in terms of hard endpoints. In studies conducted in developed countries, the baseline quality of AMI care is generally superior to that observed in our country.<sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup> Thus, demonstrating the magnitude of the incremental benefit of any intervention is more difficult to obtain in this situation, while in places where there is poor quality and care delivery, less complex interventions may have a greater impact on outcomes. A previous evaluation of adherence to AMI quality of care criteria in MG illustrates this care gap in the region.<sup><xref ref-type="bibr" rid="B21">21</xref> - <xref ref-type="bibr" rid="B23">23</xref></sup> Despite the fact that the implementation of prehospital care was not part of the implementation of AMI systems of care, interventional facilities or dedicated cardiac care units in those regions, it may have influenced the improvement of the quality of care during the study period, since a higher proportion of patients might have received accurate diagnosis and appropriate treatment.</p>
        <p>Outcomes associated with AMI are related to multiple variables, especially the structure for the care of patients.<sup><xref ref-type="bibr" rid="B22">22</xref> - <xref ref-type="bibr" rid="B24">24</xref></sup> It is worth highlighting some relevant elements in the formulation of a high complexity network in cardiology: 1) the inverse relationship between the size and volume of procedures performed in referral hospitals and AMI mortality: 2) benefit of the &#8220;pharmaco-invasive&#8221; strategy, which consists of prehospital or early in-hospital fibrinolysis followed by routine PCI between 3 and 24 hours, comparable to primary PCI in patients with short-term AMI-related symptoms, whenever a timely transfer to a PCI-capable units is possible;<sup><xref ref-type="bibr" rid="B19">19</xref></sup> 3) the cost-effectiveness of prehospital care expansion in relation to the construction of new interventional cardiology services, which was demonstrated in the USA, where the distance to hemodynamic services is around 70 km in the vast majority of sites.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup></p>
        <p>As expected, there was greater variation of rates in places with smaller populations, such as in the eastern and central-southern regions of the state, which have the lower HDIs of the state, respectively covered by the CISDESTE and CISRU consortia. This finding is possibly associated with the lower quality of the death certificate filling, with a higher proportion of deaths from undefined causes and &#8220;garbage codes&#8221; (health conditions that cannot be directly attributable to mortality), associated with the influence of other causes of mortality in those populations, such as infectious diseases, consistent with that observed in other low HDI regions in Brazil and worldwide (WHO, 2017).<sup><xref ref-type="bibr" rid="B24">24</xref> - <xref ref-type="bibr" rid="B26">26</xref></sup> This finding reiterates the importance of using analytical adjustment methods for extreme variations. In this sense, the methodological analysis applying the global empirical Bayes method was effective in reducing the variation of rates in small populations, without changing the values in places with larger populations, as shown in <xref ref-type="fig" rid="f04001">Figure 4</xref> . The use of the rates observed in the state of MG as a reference for smoothing allowed this process to be done with a reference population similar to the analyzed municipalities, but with a larger population.</p>
        <p>
          <fig id="f04001">
            <label>Figure 4</label>
            <caption>
              <title>Annual crude mortality rates in the state of Minas Gerais from 2008 to 2016. A temporal reduction trend.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-119-05-0756-10953-gf04-en.tif"/></fig>
        </p>
        <p>With regards to seasonal variation in AMI mortality rates, this variation was not expected in a region with much lower temperature variation compared to North American or European countries, or even cooler regions of Brazil, such as S&#227;o Paulo and the South Region. It raises the possibility of explanations other than the temperature, or temperature-related physiological changes, such as changes in blood viscosity, platelet volume, and blood pressure.<sup><xref ref-type="bibr" rid="B27">27</xref></sup> Other diseases that are more common during the winter, especially respiratory infections by viruses and community-acquired pneumonia have shown to affect the cardiovascular system in various ways and to precipitate adverse cardiac outcomes, such as heart failure, myocardial infarction, and cardiac arrhythmias.<sup><xref ref-type="bibr" rid="B28">28</xref></sup> As coronary artery disease is essentially an inflammatory disease, it has been shown that inflammation related to respiratory pathogens can trigger it.<sup><xref ref-type="bibr" rid="B29">29</xref></sup> In a self-controlled case series using national infection surveillance data linked to the Scottish Morbidity Record, AMI and stroke rates substantially increased in the week following a respiratory infection.<sup><xref ref-type="bibr" rid="B30">30</xref></sup> In addition, a recent meta-analysis has shown the impact of the 23-valent polysaccharide pneumococcal vaccine in providing protection from any cardiovascular event (risk ratio [RR]: 0.91; 95% CI: 0.84 to 0.99), myocardial infarction (RR: 0.88; 95% CI: 0.79 to 0.98), and all-cause mortality (RR: 0.78; 95% CI: 0.68 to 0.88) in individuals of all age groups.<sup><xref ref-type="bibr" rid="B31">31</xref></sup> On the other hand, an ongoing clinical trial conducted in Brazil comparing single- to double-dose influenza vaccine after an acute coronary event was interrupted early due to apparent lack of benefit in interim analyses.<sup><xref ref-type="bibr" rid="B32">32</xref></sup></p>
        <p>Air pollution, especially exposure to particulate matter, has also been associated with a higher risk of cardiovascular diseases, including AMI.<sup><xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B34">34</xref></sup> A recent study has observed that an increase of around 10 micrograms per m<sup>3</sup>of air was associated with an increase of 16% of AMI mortality.<sup><xref ref-type="bibr" rid="B33">33</xref></sup> Meanwhile, another study using a global atmospheric chemistry model has shown that over 60% of cardiovascular deaths worldwide have been related to air pollution, and short-term increases in air pollution are associated to AMI.<sup><xref ref-type="bibr" rid="B34">34</xref></sup> Sunyer et al., observed that the increase in sulfur dioxide levels in the air of seven European cities increased hospital admissions for cardiovascular diseases on the previous day and on the day of higher pollutant levels.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> This association remained significant even after adjusting for particles with size lower than 10 &#956;m among subjects younger than 65 years. Air pollution tends to be higher in months in which rain levels are lower. Therefore, in Brazil, where the summers are rainy while winters have predominantly drier weather, seasonality may play an important role in AMI mortality indeed.</p>
        <p>Our study has some limitations that should be addressed. The implementation of prehospital care is accompanied by co-interventions, such as articulation of the linkage of healthcare institutions of the AMI care system and increased local emergency services, which were not systematically studied in this study, and may have influenced the findings. Through public information available from the Ministry of Health, Minas Gerais State Health Secretariat, Municipal Health Secretariats and SAMUs&#8217; databases, it is possible to affirm that the available networks were incipient and that there was a lack of infrastructure, supplies, human resources, and organizational and management processes in the majority of the state and the country.<sup><xref ref-type="bibr" rid="B11">11</xref> , <xref ref-type="bibr" rid="B13">13</xref> , <xref ref-type="bibr" rid="B14">14</xref></sup> Examples include the low availability of interventional cardiology services and the concentration of health resources in regions with better sociodemographic profiles; the low utilization of telehealth services by prehospital teams; the absence of fibrinolytics in SAMU ambulances; the lack of clinical protocols and standardization of evidence-based care; the poor infrastructure of most emergency departments in the state, mostly prehospital emergency units and small hospitals; and the suboptimal training of health personnel involved in emergency care. Finally, these factors add to the difficulty of implementing the health care networks due to financial and political reasons.</p>
        <p>This study did not address the impact of other levels of attention on the outcomes studied, such as primary health care (PHC). Although there are consistent data in the literature showing the key role of PHC in the prevention, promotion, and treatment of health conditions that are risk factors for AMI, with its ability to reduce the incidence rates of AMI, the focus of this study was acute events, which occur, albeit to a lesser extent, in well-established PHC systems.<sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref> , <xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B20">20</xref></sup> As the health effects associated with PHC are typically observed over the long term, no adjustment was made for this variable, given the technical difficulties inherent in this process and the scarcity of databases to perform it.</p>
        <p>Another limitation is related to the fact that the ecological model does not include relevant individual clinical variables; therefore, it is not possible to establish relationships between such characteristics and the outcomes studied or to establish a definitive causal relationship between the implementation of SAMU and these outcomes. Finally, like all observational studies, the risk of bias has been minimized but cannot be completely excluded, in particular residual confounding bias.</p>
        <p>Nevertheless, the major strength of our study is its methodological contribution, i.e., presenting a method that can take into account the seasonality and temporal trends to observe the effect of an intervention. The temporal trend of mortality reduction was taken into account in the analysis, and mortality reduction with SAMU implementation was observed regardless of this temporal trend.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>In the present study, a small reduction in general and in-hospital mortality rates attributable to AMI was observed following the implementation of SAMU in the Brazilian state of MG in the time frame analyzed, with no significant changes in hospital admission rates. Results suggest that prehospital care plays an important role in the healthcare system, especially considering the growing burden of cardiovascular diseases, especially acute coronary syndromes.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>Study Association</p>
          <p>This article is part of the Master thesis submitted by Rodrigo Costa Pereira Vieira, from Universidade Federal de Minas Gerais.</p>
        </fn>
        <fn fn-type="other">
          <p>Ethics approval and consent to participate</p>
          <p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>Sources of Funding: This study was partially funded by CNPq (310790/2021-2), FAPEMIG ( PPM-00428-17 and RED-00081-16) and by IATS/CNPq [grant number 147122/2021-0].</p>
        </fn>
      </fn-group>
      <app-group>
        <app id="app01">
          <title>* Supplemental Materials</title>
          <p>For additional information, please <ext-link ext-link-type="uri" xlink:href="http://abccardiol.org/supplementary-material/2022/11905/2021-0953-supplemental.pdf">click here</ext-link>.</p>
        </app>
      </app-group>
    </back>
  </sub-article>
</article>
