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          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Efetividade &#40;QALY&#41; e custos incrementais dos NOAC relativamente &#224; varfarina&#46;</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">NOAC&#58; non&#8208;vitamin K antagonist oral anticoagulants&#59; QALY&#58; quality&#8208;adjusted life years&#59; ICER&#58; incremental cost&#8208;effectiveness <span class="elsevierStyleItalic">ratio</span>&#46;</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Este gr&#225;fico compara a efetividade &#40;QALY&#41; e os custos incrementais dos NOAC relativamente &#224; varfarina &#40;representada na coordenada 0&#44;0&#41;&#46; A linha vermelha representa a fronteira de custo&#8208;efetividade&#46; A sua inclina&#231;&#227;o em cada segmento corresponde ao ICER entre os pontos definindo esse segmento&#46; Os NOAC com menos QALY incrementais localizam&#8208;se mais &#224; esquerda e os NOAC com maiores custos incrementais localizam&#8208;se mais acima&#46; O apixabano constitui uma op&#231;&#227;o terap&#234;utica com custos incrementais de 1064<span class="elsevierStyleHsp" style=""></span>&#8364; face aos da varfarina&#44; mas apresenta a maior efetividade comparativamente a todas as alternativas terap&#234;uticas&#46; Os pontos &#224; esquerda da linha s&#227;o dominados por combina&#231;&#245;es de terap&#234;uticas mais efectivas que na fronteira&#46; Neste caso&#44; o rivaroxabano &#233; estritamente dominado pelo apixabano&#44; apresentando menos QALY e mais custos&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introdu&#231;&#227;o</span><p id="par0295" class="elsevierStylePara elsevierViewall">A fibrilha&#231;&#227;o auricular &#40;FA&#41; &#233; a arritmia persistente mais prevalente na pr&#225;tica cl&#237;nica&#46; Em Portugal estima&#8208;se que 2&#44;5&#37; dos indiv&#237;duos com mais de 40 anos tenham FA&#44; sendo a preval&#234;ncia superior a 10&#37; nos indiv&#237;duos com mais de 80 anos<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">1</span></a>&#46; Uma vez que a FA pode ser assintom&#225;tica e permanecer sem diagn&#243;stico at&#233; que ocorra uma complica&#231;&#227;o &#40;acidente vascular cerebral &#91;AVC&#93; isqu&#233;mico ou embolia perif&#233;rica sist&#233;mica&#41;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">2&#44;3</span></a>&#44; est&#225; atualmente recomendado o seu rastreio cl&#237;nico em todos os doentes com mais de 65 anos&#46; O conhecimento desta condi&#231;&#227;o &#233; essencial para estratificar o risco tromboemb&#243;lico e decidir sobre a institui&#231;&#227;o de medica&#231;&#227;o profil&#225;tica das complica&#231;&#245;es tromboemb&#243;licas associadas&#46; A anticoagula&#231;&#227;o oral com antagonistas da vitamina K &#233; a principal interven&#231;&#227;o farmacol&#243;gica utilizada com este objetivo&#44; estando associada a uma redu&#231;&#227;o superior a 50&#37; do risco de AVC em doentes com FA<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">4</span></a>&#46; Apesar da efic&#225;cia verificada em ensaios cl&#237;nicos&#44; a utiliza&#231;&#227;o destes f&#225;rmacos tem sido consistentemente reportada como sub&#243;tima<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Mais recentemente&#44; surgiram novas op&#231;&#245;es farmacol&#243;gicas com os mesmos objetivos terap&#234;uticos&#44; nomeadamente os designados novos anticoagulantes orais &#8211; <span class="elsevierStyleItalic">non&#8208;vitamin K antagonist oral anticoagulants</span> &#40;NOAC&#41;&#46; A sua efic&#225;cia &#233; considerada&#44; pelo menos&#44; similar aos antagonistas da vitamina K<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">6</span></a>&#44; com menor risco de hemorragia intracraniana<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">7</span></a> e sem necessidade de controlo laboratorial da hemostase do <span class="elsevierStyleItalic">international normalized ratio</span> &#40;INR&#41;&#46; At&#233; &#224; data&#44; foram comparticipados para a FA em Portugal tr&#234;s destes NOAC&#58; apixabano&#44; dabigatrano e rivaroxabano&#46; Estes f&#225;rmacos s&#227;o distintos&#44; com mecanismos de a&#231;&#227;o&#44; caracter&#237;sticas farmacocin&#233;ticas e regimes posol&#243;gicos diferentes que influenciam a op&#231;&#227;o terap&#234;utica entre eles perante o doente individual&#44; como sejam o grau de disfun&#231;&#227;o renal&#44; a idade&#44; o risco hemorr&#225;gico&#44; a hist&#243;ria pr&#233;via de doen&#231;a coron&#225;ria ou arterial perif&#233;rica e o risco de AVC&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Apesar do impacto or&#231;amental associado a estes novos medicamentos&#44; os estudos j&#225; publicados sobre o custo&#8208;efetividade de dabigatrano e rivaroxabano <span class="elsevierStyleItalic">versus</span> varfarina na FA para a realidade portuguesa indicam que a utiliza&#231;&#227;o destas interven&#231;&#245;es na pr&#225;tica cl&#237;nica portuguesa &#233; custo&#8208;efetiva<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; Desde um de agosto de 2014&#44; estes NOAC foram comparticipados pelo Servi&#231;o Nacional de Sa&#250;de &#40;SNS&#41; para a preven&#231;&#227;o de eventos tromboemb&#243;licos em doentes com FA n&#227;o&#8208;valvular&#46; Neste contexto&#44; &#233; relevante&#44; para os diferentes decisores&#44; conhecer os ganhos em sa&#250;de e os custos associados aos diferentes NOAC&#46; O objetivo deste trabalho foi&#44; portanto&#44; estimar o custo&#8208;efetividade dos NOAC&#44; em particular do apixabano &#40;o mais recente NOAC a obter autoriza&#231;&#227;o de introdu&#231;&#227;o no mercado&#41; comparativamente a varfarina&#44; dabigatrano e rivaroxabano&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">M&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Estrutura do modelo</span><p id="par0310" class="elsevierStylePara elsevierViewall">O modelo de custo&#8208;efetividade e custo&#8208;utilidade &#233; um modelo de Markov&#44; com ciclos de seis semanas &#40;dura&#231;&#227;o m&#237;nima expect&#225;vel em que pode ocorrer altera&#231;&#227;o dos sintomas ou da patologia&#41; que segue uma coorte de 1000 doentes no horizonte temporal coincidente com o tempo de vida &#40;<span class="elsevierStyleItalic">lifetime</span>&#41;&#46; O modelo &#233; programado em <span class="elsevierStyleItalic">Excel</span> com <span class="elsevierStyleItalic">Visual Basic for Applications</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figura 1</a>&#41; e os seus detalhes foram recentemente &#40;2014&#41; publicados por Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0315" class="elsevierStylePara elsevierViewall">No modelo&#44; a hist&#243;ria natural da doen&#231;a foi representada de forma simplificada em 11 estadios de sa&#250;de mutuamente exclusivos&#58; FA n&#227;o&#8208;valvular&#59; AVC isqu&#233;mico n&#227;o&#8208;fatal ligeiro&#44; moderado e grave&#59; AVC hemorr&#225;gico n&#227;o&#8208;fatal ligeiro&#44; moderado e grave&#59; embolismo sist&#233;mico &#40;ES&#41;&#59; enfarte agudo do mioc&#225;rdio &#40;EAM&#41;&#59; FA n&#227;o&#8208;valvular em que foi descontinuada a anticoagula&#231;&#227;o inicial&#59; e morte&#46; Ap&#243;s um intervalo de seis semanas&#44; um doente poder&#225; transitar para outro est&#225;dio de acordo com a respetiva probabilidade de transi&#231;&#227;o&#46; A cada est&#225;dio est&#225; associada uma probabilidade de ocorrer um evento no intervalo de tempo considerado&#46; O risco de AVC isqu&#233;mico depende do <span class="elsevierStyleItalic">score</span> CHADS<span class="elsevierStyleInf">2</span><a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">11</span></a> &#8211; modelo de estratifica&#231;&#227;o de risco tromboemb&#243;lico utilizado &#224; data da realiza&#231;&#227;o dos ensaios cl&#237;nicos &#8211; e do n&#237;vel de adequabilidade da hipocoagula&#231;&#227;o para os doentes tratados com varfarina&#44; determinado pela mediana do tempo em que os valores do INR se encontram dentro do intervalo terap&#234;utico&#46; As probabilidades de ocorr&#234;ncia de AVC&#44; EAM&#44; outras hemorragias intracranianas e outras hemorragias <span class="elsevierStyleItalic">major</span> e <span class="elsevierStyleItalic">n&#227;o&#8208;major</span> aumentam com a idade&#44; refletindo o risco acrescido de ocorr&#234;ncia destes eventos ao longo da vida&#46; O modelo considera tamb&#233;m o impacto a longo prazo do EAM e do ES na mortalidade &#40;<span class="elsevierStyleItalic">hazard ratio</span> &#91;HR&#93; mais altos&#41;&#46; Caso o doente se encontre no est&#225;dio FA n&#227;o&#8208;valvular&#44; em que se suspendeu a anticoagula&#231;&#227;o inicial&#44; a estrutura do modelo n&#227;o se altera&#44; mas as probabilidades de transi&#231;&#227;o variam&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">No cen&#225;rio de ocorr&#234;ncia de um AVC &#40;isqu&#233;mico ou hemorr&#225;gico&#41;&#44; a distribui&#231;&#227;o da gravidade do AVC &#233; feita segundo a escala Rankin modificada &#40;mRS&#41;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">12</span></a>&#58; AVC n&#227;o&#8208;fatal ligeiro &#40;mRS&#58; 0&#8208;2&#41;&#44; moderado &#40;mRS&#58; 3&#8208;4&#41; ou grave &#40;mRS&#58; 5&#41; e AVC fatal &#40;mRS&#58; 6&#41;&#46; Todos os doentes com AVC fatal transitam para o est&#225;dio morte no ciclo seguinte&#44; enquanto os AVC n&#227;o&#8208;fatais est&#227;o modelizados como um est&#225;dio &#171;t&#250;nel&#187;&#44; ou seja&#44; estes doentes podem apenas ter uma recorr&#234;ncia de AVC ou morrer&#46; O modelo permite que cada doente tenha apenas um AVC recorrente&#46; Neste caso&#44; o doente transita para o est&#225;dio correspondente ao AVC com gravidade igual ou superior ao primeiro AVC&#46; O modelo n&#227;o considera poss&#237;vel a recorr&#234;ncia de EAM ou de ES&#46; Nestes casos&#44; o doente poder&#225; apenas manter&#8208;se nesse est&#225;dio ou transitar para o est&#225;dio morte&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">No final de cada intervalo s&#227;o estimados os custos da doen&#231;a&#44; os anos de vida ajustados pela qualidade &#40;<span class="elsevierStyleItalic">quality&#8208;adjusted life years</span> &#91;QALY&#93;&#41; e os anos de vida acrescidos&#46; Os n&#237;veis de qualidade de vida relacionada com a sa&#250;de &#40;utilidades&#41;&#44; <span class="elsevierStyleItalic">outcomes</span> cl&#237;nicos e as taxas de mortalidade variam consoante o grau de gravidade do AVC&#46; Conforme estipulado nas Orienta&#231;&#245;es Metodol&#243;gicas para Estudos de Avalia&#231;&#227;o Econ&#243;mica de Medicamentos do Infarmed<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">13</span></a>&#44; os custos e efetividades foram atualizados &#224; taxa de 5&#37;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Popula&#231;&#227;o</span><p id="par0330" class="elsevierStylePara elsevierViewall">No cen&#225;rio base&#44; a popula&#231;&#227;o considerada no modelo corresponde &#224;s caracter&#237;sticas dos doentes inclu&#237;dos nos ensaios com apixabano&#44; mais concretamente no ensaio ARISTOTLE<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">14</span></a>&#44; em termos de idade m&#233;dia &#40;70 anos&#41;&#44; g&#233;nero &#40;64&#44;7&#37; homens&#41; e distribui&#231;&#227;o dos <span class="elsevierStyleItalic">scores</span> CHADS<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">score</span> 1&#8208;2&#58; 69&#37;&#59; <span class="elsevierStyleItalic">score</span> 3&#8208;4&#58; 27&#37; e <span class="elsevierStyleItalic">score</span> 5&#8208;6&#58; 4&#37;&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Comparadores</span><p id="par0335" class="elsevierStylePara elsevierViewall">Neste estudo&#44; os resultados do tratamento com apixabano 2&#44;5&#8208;5<span class="elsevierStyleHsp" style=""></span>mg&#44; duas vezes por dia&#44; s&#227;o comparados aos resultados obtidos com&#58; 1&#41; dabigatrano&#44; na dose de 150<span class="elsevierStyleHsp" style=""></span>mg at&#233; os 80 anos e na dose de 110<span class="elsevierStyleHsp" style=""></span>mg ap&#243;s os 80 anos&#44; em doentes com risco hemorr&#225;gico elevado e nos tratados com verapamilo&#44; ambas dosagens duas vezes por dia&#46; Este grupo ser&#225; designado como dabigatrano&#59; 2&#41; rivaroxabano 15&#8208;20<span class="elsevierStyleHsp" style=""></span>mg&#44; uma vez por dia&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Efetividade relativa dos <span class="elsevierStyleItalic">non&#8208;vitamin K antagonist oral anticoagulants</span>&#58; compara&#231;&#245;es indiretas</span><p id="par0340" class="elsevierStylePara elsevierViewall">Os estudos de avalia&#231;&#227;o econ&#243;mica de novas tecnologias em sa&#250;de &#40;por exemplo&#44; medicamentos&#41; dependem da efetividade dessas tecnologias e dos custos associados &#224;s mesmas&#44; comparativamente &#224;s op&#231;&#245;es existentes&#46; Neste contexto&#44; a estimativa da efetividade relativa dos NOAC &#233; um dos aspetos centrais neste estudo&#46; At&#233; &#224; data&#44; n&#227;o existem compara&#231;&#245;es diretas entre os NOAC &#40;ensaios <span class="elsevierStyleItalic">head&#8208;to&#8208;head</span>&#41;&#44; pelo que as efetividades na FA t&#234;m de ser estimadas com an&#225;lise de compara&#231;&#227;o indireta&#44; utilizando um comparador comum &#40;neste caso&#44; a varfarina&#41;&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">Neste contexto&#44; torna&#8208;se fundamental avaliar a consist&#234;ncia das estimativas da efetividade utilizadas no modelo econ&#243;mico&#46; Para tal&#44; realiz&#225;mos uma revis&#227;o sistem&#225;tica da literatura para identificar as compara&#231;&#245;es indiretas publicadas entre os NOAC que disponibilizassem dados de efetividade relativa na FA&#46; Utiliz&#225;mos os termos <span class="elsevierStyleItalic">meta&#8208;analysis&#44; indirect comparison&#44; bayesian&#44; network&#44; apixaban&#44; dabigatran&#44; rivaroxaban e atrial fibrillation</span>&#44; nas bases de dados MEDLINE e <span class="elsevierStyleItalic">Cochrane Library</span> &#40;setembro de 2014&#41;&#46; Identific&#225;mos dez compara&#231;&#245;es indiretas&#58; seis do tipo frequencista<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">10&#44;15&#8211;19</span></a> e quatro do tipo <span class="elsevierStyleItalic">bayesiano</span> &#40;meta&#8208;an&#225;lises em rede&#41;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">6&#44;20&#8211;22</span></a>&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">A <a class="elsevierStyleCrossRef" href="#tbl0005">Tabela 1</a> mostra as caracter&#237;sticas sum&#225;rias de cada uma destas compara&#231;&#245;es indiretas&#46; Conforme se pode verificar na <a class="elsevierStyleCrossRef" href="#fig0010">Figura 2</a>&#44; as estimativas destas publica&#231;&#245;es para os v&#225;rios resultados &#40;<span class="elsevierStyleItalic">outcomes</span>&#41; que o modelo considera s&#227;o consistentes entre si e semelhantes &#224;s utilizadas no caso base no modelo econ&#243;mico &#40;Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a>&#41;&#46; Dado o objetivo do presente estudo&#44; os dados reportados por Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a> &#40;compara&#231;&#227;o indireta frequencista pelo m&#233;todo de Bucher<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">23</span></a>&#41; e por Mitchell et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a> &#40;meta&#8208;an&#225;lise em rede do tipo bayesiano&#41; correspondem provavelmente &#224;s melhores estimativas das efetividades relativas entre os tr&#234;s NOAC na FA&#44; por utilizarem apenas os dados dos ensaios cl&#237;nicos de fase III destes NOAC e por estabelecerem associa&#231;&#245;es utilizando o HR&#44; que tem em conta o fator temporal e respeita a an&#225;lise estat&#237;stica prim&#225;ria de cada ensaio&#46; A Figura 3&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar &#40;Anexo&#41;</a> mostra a rede de evid&#234;ncia utilizada por estas duas compara&#231;&#245;es indiretas&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Efetividade relativa dos <span class="elsevierStyleItalic">non&#8208;vitamin K antagonist oral anticoagulants</span>&#58; taxas de eventos</span><p id="par0355" class="elsevierStylePara elsevierViewall">As taxas de eventos consideradas no cen&#225;rio base do modelo s&#227;o aquelas resultantes dos HR reportadas por Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Tabela 2</a>&#41;&#46; A distribui&#231;&#227;o dos eventos de AVC por gravidade &#233; apresentada no Anexo &#40;Tabela 3&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0360" class="elsevierStylePara elsevierViewall">Como mencionado anteriormente&#44; o risco de AVC isqu&#233;mico e de eventos hemorr&#225;gicos associados ao uso de varfarina depende do n&#237;vel de adequabilidade da hipocoagula&#231;&#227;o &#40;controlo dos valores de INR&#41; &#40;Tabela 4&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar</a>&#41;&#46; O modelo distribui os doentes em quatro categorias&#44; de acordo com v&#225;rios <span class="elsevierStyleItalic">cut&#8208;offs</span> para o <span class="elsevierStyleItalic">center&#39;s median time in therapeutic range</span> &#40;cTTR&#41;&#44; conforme resultados obtidos nos v&#225;rios centros que participaram no ensaio ARISTOTLE&#46; Esta distribui&#231;&#227;o &#233; uniforme&#44; ou seja&#44; 25&#37; dos doentes em cada categoria&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">Para parametrizar o modelo de acordo com a realidade portuguesa&#44; em termos do n&#237;vel de adequabilidade da hipocoagula&#231;&#227;o&#44; utiliz&#225;mos os dados de uma amostra de conveni&#234;ncia proveniente da Consulta de Hipocoagula&#231;&#227;o do Centro Hospitalar Lisboa Central&#44; EPE &#40;CHLC&#41; e do Hospital Fernando da Fonseca&#44; EPE &#40;HFF&#41;&#46; Estes dados referem&#8208;se ao per&#237;odo entre 2011&#8208;2012 e incluem todos os doentes com&#44; pelo menos&#44; dez registos de INR&#44; no total 39<span class="elsevierStyleHsp" style=""></span>630 medi&#231;&#245;es de INR respeitantes a 2850 doentes&#46; Com base nestes dados&#44; foi calculada a mediana da propor&#231;&#227;o de tempo em que os valores de INR de um doente se encontravam no alvo terap&#234;utico &#40;propor&#231;&#227;o de tempo no alvo terap&#234;utico &#91;PTAT&#93;&#41;&#46; Dado que a informa&#231;&#227;o &#233; limitada a dois hospitais&#44; n&#227;o &#233; poss&#237;vel estimar a mediana do tempo no alvo terap&#234;utico de v&#225;rios centros &#40;cTTR&#41;&#44; mas apenas a mediana da PTAT dos doentes avaliados nestes dois hospitais&#46; Esta medida foi considerada uma aproxima&#231;&#227;o do cTTR definido no modelo&#46; A robustez dos resultados obtidos a partir desta amostra de base hospitalar foi verificada contra uma amostra com avalia&#231;&#245;es de INR em unidades de base ambulat&#243;ria&#44; que incluiu 4470 medi&#231;&#245;es de INR respeitantes a 233 doentes&#44; n&#227;o tendo sido detetadas diferen&#231;as estatisticamente significativas&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">Com base nestes dados&#44; verifica&#8208;se que o n&#237;vel de adequabilidade da hipocoagula&#231;&#227;o na amostra portuguesa &#233; inferior &#224; considerada no modelo&#44; uma vez que 44&#44;5&#37; dos doentes portugueses t&#234;m uma PTAT<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>52&#44;38&#37; e no modelo &#233; considerado que 75&#37; dos doentes tinham um cTTR<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>52&#44;38&#37; &#40;Tabela 5&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar</a>&#41;&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">As taxas de descontinua&#231;&#227;o de tratamento por 100 pessoas&#47;ano devido a causas n&#227;o vasculares foram obtidas a partir de uma an&#225;lise secund&#225;ria dos dados do ensaio ARISTOTLE &#40;13&#44;2&#37; com apixabano e 14&#44;4&#37; com varfarina&#41;&#46; Assumiu&#8208;se que as taxas foram constantes ao longo do tempo&#46; A Tabela 6&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar</a> mostra os HR de descontinua&#231;&#227;o de tratamento por causas n&#227;o devidas aos eventos vasculares&#46; A segunda linha de tratamento considerada foi &#225;cido acetilsalic&#237;lico&#46; Os riscos absolutos associados aos eventos por 100 pessoas&#47;ano s&#227;o resumidos na Tabela 7&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar</a>&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Custos</span><p id="par0380" class="elsevierStylePara elsevierViewall">O estudo adota a perspetiva do SNS&#46; Por conseguinte&#44; n&#227;o est&#227;o inclu&#237;dos na an&#225;lise os custos indiretos&#46; Deste modo&#44; o modelo identifica tr&#234;s fontes principais de custos&#58; custos gerados pela ocorr&#234;ncia dos eventos vasculares&#44; custos da terap&#234;utica anticoagulante e custos das consultas de monitoriza&#231;&#227;o e&#47;ou de rotina&#46; O custeio baseou&#8208;se&#58; 1&#41; na Portaria n&#46;&#176; 20&#47;2014 de 29 de janeiro<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">24</span></a> para efeitos dos pre&#231;os unit&#225;rios das consultas&#44; dos meios complementares de diagn&#243;stico e terap&#234;utica &#40;MCDT&#41; e dos grupos de diagn&#243;stico homog&#233;neos &#40;GDH&#41;&#59; 2&#41; na an&#225;lise da base de dados dos internamentos &#40;GDH&#41; no SNS em 2013<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">25</span></a>&#59; 3&#41; na base de dados de medicamentos do Infarmed &#40;Infomed&#41;&#44; que disponibiliza informa&#231;&#227;o relativa aos pre&#231;os dos medicamentos &#40;consultada em dois de janeiro de 2015&#41;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">26</span></a>&#59; e 4&#41; nos resultados da consulta de um painel de peritos de v&#225;rias especialidades com representatividade geogr&#225;fica&#44; que estimaram os consumos de recursos de sa&#250;de em ambulat&#243;rio&#46; Para os est&#225;dios de sa&#250;de AVC isqu&#233;mico e hemorr&#225;gico n&#227;o&#8208;fatais&#44; EAM e ES&#44; os custos foram estimados distinguindo duas fases&#58; aguda e de manuten&#231;&#227;o a longo prazo&#46; Os consumos imputados &#224; fase aguda incluem as duas primeiras semanas de internamento e a reabilita&#231;&#227;o ao longo dos primeiros tr&#234;s meses&#46; O modelo assume que a fase de manuten&#231;&#227;o dura at&#233; &#224; morte&#46; De acordo com o painel de peritos&#44; a fase de manuten&#231;&#227;o inclui custos associados a consultas&#44; epis&#243;dios de urg&#234;ncia e desloca&#231;&#245;es&#44; MCDT&#44; medica&#231;&#227;o e ajudas t&#233;cnicas&#46; N&#227;o foi poss&#237;vel estimar de forma consistente o custo dos AVC em fun&#231;&#227;o da sua gravidade &#40;ligeiro&#44; moderado e grave&#41;&#44; uma vez que n&#227;o existem dados de custo por mRS em Portugal&#46; Para os restantes est&#225;dios de sa&#250;de foram imputados apenas os custos de internamento &#40;fase aguda&#41;&#46;</p><p id="par0385" class="elsevierStylePara elsevierViewall">Os resultados dos custos globais por evento&#44; dos custos da terap&#234;utica e dos custos de monitoriza&#231;&#227;o e rotina s&#227;o reportados na <a class="elsevierStyleCrossRef" href="#tbl0015">Tabela 8</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Mortalidade</span><p id="par0390" class="elsevierStylePara elsevierViewall">As probabilidades de morte associadas aos eventos vasculares considerados no modelo foram aquelas observadas nos ensaios&#44; com exce&#231;&#227;o da taxa de letalidade do EAM&#44; a qual foi obtida a partir de Scarborough et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">27</span></a>&#46; O modelo assume que estas probabilidades s&#227;o independentes do tratamento&#46; Para o per&#237;odo que corresponde &#224; dura&#231;&#227;o do ensaio ARISTOTLE&#44; a taxa de mortalidade por outras causas&#44; que n&#227;o pelos eventos vasculares considerados no modelo&#44; assumiu&#8208;se igual para todos os NOAC&#44; utilizando&#8208;se o valor do ensaio ARISTOTLE &#40;3&#44;08&#37; para o apixabano e 3&#44;34&#37; para a varfarina&#41;&#46; A mortalidade ap&#243;s o per&#237;odo avaliado nos ensaios cl&#237;nicos foi modelizada com base nas t&#225;buas de mortalidade portuguesas<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">28</span></a> e multiplicada pelo HR associado &#224; popula&#231;&#227;o com FA estimado por Friberg et al&#46; com o objetivo de ter em conta o risco acrescido da popula&#231;&#227;o considerada<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">29</span></a>&#46; Em particular&#44; foram estimados os par&#226;metros duma fun&#231;&#227;o de sobreviv&#234;ncia Gompertz por faixa et&#225;ria &#40;&#60;<span class="elsevierStyleHsp" style=""></span>75 anos ou &#8805;<span class="elsevierStyleHsp" style=""></span>75 anos&#41; e por sexo&#46; O modelo considera fatores de ajustamento do risco de mortalidade para incluir na an&#225;lise os aumentos das taxas de mortalidade associadas &#224; FA e AVC por grau de gravidade &#40;Tabela 9&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar</a>&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Ponderadores de qualidade de vida relacionada com a sa&#250;de &#8211; utilidades</span><p id="par0395" class="elsevierStylePara elsevierViewall">Os valores m&#233;dios de utilidade da popula&#231;&#227;o e os decrementos associados aos v&#225;rios est&#225;dios da doen&#231;a foram considerados iguais aos valores brit&#226;nicos estimados por Sullivan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">30</span></a> Existem tamb&#233;m decrementos de utilidade associados &#224; terap&#234;utica com varfarina<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">31</span></a> &#40;contrariamente &#224; terap&#234;utica com NOAC&#41; e &#224; ocorr&#234;ncia de outros eventos vasculares&#46; O modelo assume que estes decrementos podem ser aplicados aditivamente&#46; A <a class="elsevierStyleCrossRef" href="#tbl0020">Tabela 10</a> resume as utilidades consideradas e os seus decrementos&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">An&#225;lise de sensibilidade</span><p id="par0400" class="elsevierStylePara elsevierViewall">Foram realizadas an&#225;lises de sensibilidade univariadas para verificar a robustez dos resultados em rela&#231;&#227;o aos seguintes par&#226;metros&#58; 1&#41; utiliza&#231;&#227;o dos HR estimados por Mitchell et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a> &#40;meta&#8208;an&#225;lise em rede do tipo <span class="elsevierStyleItalic">bayesiano</span>&#41;&#44; em vez dos estimados por Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a>&#59; 2&#41; n&#237;veis de adequabilidade do controlo de hipocoagula&#231;&#227;o como verificado nos ensaios&#44; em vez dos valores obtidos em doentes portugueses&#59; 3&#41; dura&#231;&#227;o da fase aguda dos epis&#243;dios de internamento de seis semanas&#44; em vez de duas semanas&#59; 4&#41; custos de AVC diferentes dependentes do seu n&#237;vel de gravidade com pondera&#231;&#227;o calculada a partir das estimativas inglesas&#44; em vez do custo uniforme de AVC para qualquer n&#237;vel de gravidade&#59; 5&#41; distribui&#231;&#227;o dos eventos de AVC por gravidade similar para todos os NOAC &#40;assumindo a distribui&#231;&#227;o do apixabano&#41;&#59; 6&#41; taxas de descontinua&#231;&#227;o do tratamento por outras causas &#40;que n&#227;o pelos eventos vasculares&#41; igual &#224; do apixabano &#40;13&#44;2&#37;&#47;ano&#41; para todos os comparadores desde o in&#237;cio do tratamento&#44; em vez das taxas de descontinua&#231;&#227;o reportadas nos ensaios&#59; 7&#41; taxas de mortalidade ap&#243;s o per&#237;odo avaliado no ensaio&#44; iguais &#224;s da popula&#231;&#227;o em geral&#44; com consequente subestimativas das taxas de mortalidade&#59; 8&#41; utiliza&#231;&#227;o de diferentes utilidades associadas a cada est&#225;dio &#40;como estimadas na publica&#231;&#227;o precedente de Sullivan et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">46</span></a> e utilizadas noutros estudos de custo&#8208;efetividade de NOAC<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">32&#8211;34</span></a>&#41;&#59; 9&#41; taxa de atualiza&#231;&#227;o de custos e utilidades &#40;0 ou 3&#37;&#44; em vez de 5&#37;&#41;&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall">Foi tamb&#233;m realizada uma an&#225;lise probabil&#237;stica de sensibilidade&#44; utilizando simula&#231;&#245;es de Monte&#8208;Carlo &#40;2000 simula&#231;&#245;es&#41; incorporando incerteza de segunda ordem<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">35</span></a>&#46; Os resultados s&#227;o apresentados como a probabilidade do apixabano ser custo&#8208;efetivo <span class="elsevierStyleItalic">versus</span> outras op&#231;&#245;es terap&#234;uticas utilizando um <span class="elsevierStyleItalic">threshold</span> de 20<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>&#8364; por QALY&#44; limiar habitualmente considerado como aceit&#225;vel para o financiamento de novas tecnologias de sa&#250;de em Portugal&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Resultados</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Taxa de eventos e custos</span><p id="par0410" class="elsevierStylePara elsevierViewall">A <a class="elsevierStyleCrossRef" href="#tbl0025">Tabela 11</a> resume o n&#250;mero de eventos vasculares com cada anticoagulante numa coorte de 100<span class="elsevierStyleHsp" style=""></span>000 doentes conforme as taxas resultantes do modelo&#46; De salientar que o n&#250;mero de eventos vasculares e &#243;bitos relacionados com eventos cl&#237;nicos &#233; menor com apixabano&#44; exceto no caso de AVC hemorr&#225;gico&#46; Esta diferen&#231;a no n&#250;mero de eventos <span class="elsevierStyleItalic">versus</span> as outras op&#231;&#245;es terap&#234;uticas &#233; de maior magnitude no caso do AVC isqu&#233;mico&#44; outras hemorragias <span class="elsevierStyleItalic">major</span>&#44; hemorragias n&#227;o&#8208;<span class="elsevierStyleItalic">major</span> clinicamente relevantes e &#243;bitos relacionados com eventos cl&#237;nicos&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0415" class="elsevierStylePara elsevierViewall">A <a class="elsevierStyleCrossRef" href="#tbl0030">Tabela 12</a> e a <a class="elsevierStyleCrossRef" href="#fig0015">Figura 4</a> resumem os custos associados &#224;s diferentes op&#231;&#245;es e a sua estrutura&#46; A terap&#234;utica com varfarina &#233; a op&#231;&#227;o com menor custo total m&#233;dio por doente e a terap&#234;utica com rivaroxabano a mais dispendiosa&#46; O custo total m&#233;dio por doente com apixabano &#8211; considerando o horizonte temporal da an&#225;lise &#40;<span class="elsevierStyleItalic">lifetime</span>&#41; &#8211; situa&#8208;se neste intervalo&#46; O apixabano &#233; a op&#231;&#227;o com menores custos cl&#237;nicos &#40;dado estar associado a uma menor taxa de eventos vasculares&#41; e com menores custos relacionados com monitoriza&#231;&#227;o e cuidados de rotina&#46; Os custos da terap&#234;utica com apixabano ao longo da vida s&#227;o maiores dada a maior dura&#231;&#227;o de tratamento&#44; a qual&#44; por sua vez&#44; &#233; devida &#224; menor descontinua&#231;&#227;o da terap&#234;utica&#46; Assim&#44; apesar do custo di&#225;rio do apixabano ser inferior ao de dabigatrano e rivaroxabano&#44; os custos da terap&#234;utica com apixabano s&#227;o maiores quando se considera o horizonte temporal coincidente com o tempo de vida&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Custo&#8208;efetividade de apixabano <span class="elsevierStyleItalic">versus</span> outras op&#231;&#245;es terap&#234;uticas</span><p id="par0420" class="elsevierStylePara elsevierViewall">A <a class="elsevierStyleCrossRef" href="#tbl0035">Tabela 13</a> e a <a class="elsevierStyleCrossRef" href="#fig0020">Figura 5</a> mostram os resultados da an&#225;lise de custo&#8208;efetividade de apixabano <span class="elsevierStyleItalic">versus</span> as outras op&#231;&#245;es terap&#234;uticas&#46; Como sugerido na literatura<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">36&#44;37</span></a>&#44; no caso das compara&#231;&#245;es m&#250;ltiplas&#44; apresentam&#8208;se os resultados num gr&#225;fico onde as abcissas representam a diferen&#231;a de QALY e as ordenadas a diferen&#231;a de custo entre os comparadores e uma terap&#234;utica de refer&#234;ncia &#40;<span class="elsevierStyleItalic">i&#46;e&#46;</span> varfarina&#41;&#46; A linha vermelha que une os pontos do gr&#225;fico representa a fronteira de efici&#234;ncia&#46; A fronteira &#233; caracterizada por tr&#234;s tra&#231;os&#58; a sua inclina&#231;&#227;o &#233; de 4367<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY quando une os pontos representantes da varfarina e de dabigatrano&#59; de 9163<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY quando une os pontos de dabigatrano e do apixabano&#44; e &#233; vertical a partir do apixabano porque n&#227;o existe tecnologia mais efetiva&#46; O rivaroxabano &#233; dominado porque se encontra &#224; esquerda da fronteira de custo&#8208;efetividade &#40;apresentando mais custos e menos QALY que as combina&#231;&#245;es das alternativas terap&#234;uticas na fronteira&#41;&#46; O rivaroxabano &#233;&#44; ali&#225;s&#44; dominado pelo apixabano considerado isoladamente&#46;</p><elsevierMultimedia ident="tbl0035"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">An&#225;lise de sensibilidade</span><p id="par0425" class="elsevierStylePara elsevierViewall">Os resultados da an&#225;lise de sensibilidade univariada e probabil&#237;stica suportam a robustez dos resultados obtidos&#46; Na an&#225;lise unidimensional para os nove par&#226;metros antes mencionados&#44; e que refletem um conjunto de cen&#225;rios alternativos&#44; o apixabano &#233; sempre dominante relativamente ao rivaroxabano&#46; Comparativamente &#224;s restantes op&#231;&#245;es&#44; em oito dos nove cen&#225;rios considerados&#44; o apixabano apresenta ICER muito inferiores a 20<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#44; variando entre 4909 e 6741<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY <span class="elsevierStyleItalic">versus</span> varfarina e entre 5162 e 12<span class="elsevierStyleHsp" style=""></span>016<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY <span class="elsevierStyleItalic">versus</span> dabigatrano&#46; Quando se assume que as taxas de descontinua&#231;&#227;o por outras causas s&#227;o iguais desde o in&#237;cio do tratamento&#44; o apixabano induz custos menores relativamente ao rivaroxabano e ao dabigatrano&#46; Neste cen&#225;rio&#44; o apixabano &#233; dominante <span class="elsevierStyleItalic">versus</span> rivaroxabano e&#44; para um <span class="elsevierStyleItalic">threshold</span> de 20<span class="elsevierStyleHsp" style=""></span>000 <span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#44; &#233; custo&#8208;efetivo <span class="elsevierStyleItalic">versus</span> varfarina e dabigatrano&#46; Os resultados das an&#225;lises de sensibilidade s&#227;o resumidos na Tabela 14&#59; <a class="elsevierStyleCrossRef" href="#sec0130">Suplementar</a>&#41;&#46;</p><p id="par0430" class="elsevierStylePara elsevierViewall">No caso da an&#225;lise de sensibilidade probabil&#237;stica&#44; a probabilidade do apixabano ser custo&#8208;efetivo&#44; para um <span class="elsevierStyleItalic">threshold</span> de 20<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#44; &#233; de 96&#44; 87 e 95&#37; <span class="elsevierStyleItalic">versus</span> varfarina&#44; dabigatrano e rivaroxabano&#44; respetivamente&#46; Se todos os comparadores forem considerados simultaneamente &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Figura 6</a>&#41;&#44; o apixabano &#233; a melhor alternativa a partir de um <span class="elsevierStyleItalic">threshold</span> de 8000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#46; Neste cen&#225;rio&#44; para uma disposi&#231;&#227;o a pagar de 20<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#44; a probabilidade do apixabano ser custo&#8208;efetivo &#233; de 70&#37;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Discuss&#227;o</span><p id="par0435" class="elsevierStylePara elsevierViewall">A FA &#233; a arritmia card&#237;aca persistente mais prevalente<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">1</span></a> com um importante impacto social devido &#224; mortalidade e morbilidade geradas&#44; podendo atribuir&#8208;se &#224; FA 3&#44;8&#37; do total das mortes ocorridas em Portugal&#46; Em termos de carga e custos da doen&#231;a atribu&#237;vel &#224; FA para a realidade portuguesa&#44; estima&#8208;se que esta seja respons&#225;vel por cerca de 23<span class="elsevierStyleHsp" style=""></span>000 anos de vida perdidos ajustados pela incapacidade e por custos globais de cerca de 140 milh&#245;es de euros &#40;M&#8364;&#41;&#44; aproximadamente 0&#44;08&#37; do produto interno bruto<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">38</span></a>&#46; &#201; expect&#225;vel que este cen&#225;rio venha a assumir ainda maior import&#226;ncia no futuro&#44; com o aumento da incid&#234;ncia e preval&#234;ncia da FA devido ao envelhecimento da popula&#231;&#227;o e ao aumento da preval&#234;ncia de doen&#231;as card&#237;acas cr&#243;nicas&#44; entre outros fatores<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">39</span></a>&#46; Tamb&#233;m o aumento do uso de monitoriza&#231;&#227;o eletrocardiogr&#225;fica ambulat&#243;ria&#44; traduzindo&#8208;se em mais diagn&#243;sticos&#44; contribui para que&#44; neste contexto e no futuro&#44; a FA constitua uma &#225;rea onde se podem obter ganhos de sa&#250;de significativos&#46;</p><p id="par0440" class="elsevierStylePara elsevierViewall">A terap&#234;utica antitromb&#243;tica&#44; nomeadamente a anticoagula&#231;&#227;o&#44; reduz significativamente o risco de eventos cl&#237;nicos tromboemb&#243;licos relacionados com a FA&#44; nomeadamente o de AVC<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">4</span></a>&#46; Durante v&#225;rias d&#233;cadas&#44; existiram poucas op&#231;&#245;es terap&#234;uticas em termos de anticoagula&#231;&#227;o destes doentes&#44; sendo a varfarina a terap&#234;utica de refer&#234;ncia&#46; Mais recentemente&#44; surgiram no mercado novos anticoagulantes &#40;NOAC&#41;&#46; Desde a sua comparticipa&#231;&#227;o pelo SNS&#44; verificou&#8208;se um aumento muito significativo do n&#250;mero de doentes medicados com os NOAC&#44; sendo expect&#225;vel que a atual fra&#231;&#227;o dos encargos do SNS com medicamentos de ambulat&#243;rio atribu&#237;vel aos anticoagulantes &#40;4&#44;5&#37;&#44; que corresponde a uma despesa estimada superior a 50<span class="elsevierStyleHsp" style=""></span>M&#8364; em 2014&#41; venha a aumentar<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">40</span></a>&#46; Neste contexto&#44; e com o intuito de informar os v&#225;rios decisores em sa&#250;de&#44; &#233; relevante estimar o custo&#8208;efetividade relativo dos NOAC recentemente comparticipados para a preven&#231;&#227;o do AVC na FA&#46;</p><p id="par0445" class="elsevierStylePara elsevierViewall">Foram publicados v&#225;rios estudos de custo&#8208;efetividade onde cada um dos NOAC foi individualmente comparado com varfarina&#46; Sem exce&#231;&#227;o&#44; os resultados destes estudos&#44; realizados em diferentes realidades&#44; desde Europa aos EUA&#44; mostraram que os NOAC s&#227;o custo&#8208;efetivos <span class="elsevierStyleItalic">versus</span> varfarina<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">41</span></a>&#46; No entanto&#44; os resultados de custo&#8208;efetividade destes estudos n&#227;o podem ser comparados de forma indireta e <span class="elsevierStyleItalic">na&#239;ve</span> para avaliar o custo&#8208;efetividade entre NOAC e&#44; certamente&#44; n&#227;o refletem a realidade portuguesa&#46; Neste contexto&#44; realiz&#225;mos um estudo de avalia&#231;&#227;o com base num modelo econ&#243;mico previamente publicado<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a> que comparou os NOAC entre si&#44; o qual foi parametrizado para a realidade portuguesa&#46;</p><p id="par0450" class="elsevierStylePara elsevierViewall">De acordo com os resultados do presente estudo&#44; o apixabano &#233; custo&#8208;efetivo <span class="elsevierStyleItalic">versus</span> varfarina e dabigatrano &#40;ICER de 5529<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY e 9163<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#44; respetivamente&#41; e dominante <span class="elsevierStyleItalic">versus</span> rivaroxabano&#46; A probabilidade de ser custo&#8208;efetivo&#44; quando comparado simultaneamente com o conjunto das restantes alternativas terap&#234;uticas&#44; &#233; de 70&#37; considerando um <span class="elsevierStyleItalic">threshold</span> de 20<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#46; Estes resultados s&#227;o concordantes com os de outros estudos para outras realidades europeias&#44; como a B&#233;lgica<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">42</span></a>&#44; a Holanda<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">32</span></a>&#44; o Reino Unido<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">10&#44;43</span></a> e a Fran&#231;a<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">44</span></a>&#44; em que o apixabano foi tamb&#233;m custo&#8208;efetivo <span class="elsevierStyleItalic">versus</span> varfarina e custo&#8208;efetivo&#44; ou mesmo dominante&#44; <span class="elsevierStyleItalic">versus</span> dabigatrano e rivaroxabano&#46; O facto do apixabano se apresentar como o NOAC mais custo&#8208;efetivo nestes estudos&#44; deve&#8208;se possivelmente ao melhor perfil de efetividade do apixabano relativamente aos restantes NOAC&#44; o qual poder&#225; ser atribu&#237;vel a um menor n&#250;mero de eventos vasculares comparativamente &#224;s restantes op&#231;&#245;es terap&#234;uticas&#44; nomeadamente de AVC isqu&#233;mico<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">10&#44;44&#44;45</span></a>&#44; hemorragias <span class="elsevierStyleItalic">major</span><a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a> e mortes relacionadas com eventos vasculares<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">10&#44;20</span></a>&#46; Uma consequ&#234;ncia l&#243;gica &#233; que o apixabano apresenta um menor n&#250;mero de descontinua&#231;&#245;es por eventos vasculares&#44; com os doentes a permanecerem mais tempo em tratamento &#40;com os benef&#237;cios associados em termos de preven&#231;&#227;o de eventos tromboemb&#243;licos&#41;&#46; Por outro lado&#44; a menor taxa de descontinua&#231;&#227;o do tratamento justifica o aumento relativo dos custos totais da terap&#234;utica com apixabano ao longo da vida face aos outros NOAC&#46;</p><p id="par0455" class="elsevierStylePara elsevierViewall">Foram&#44; no entanto&#44; recentemente publicados outros estudos&#44; para a realidade norueguesa<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">33</span></a> e para o Reino Unido<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">32&#44;34</span></a>&#44; cujos resultados diferem dos presentes&#44; no sentido em que dabigatrano foi considerado custo&#8208;efetivo <span class="elsevierStyleItalic">versus</span> apixabano &#40;ambos superiores ao rivaroxabano&#41;&#46; Nestes estudos&#44; os QALY incrementais foram 0&#44;2 a 1&#44;3&#37; superiores com dabigatrano <span class="elsevierStyleItalic">versus</span> apixabano&#44; apesar do n&#250;mero de eventos vasculares ser determinado a partir dos mesmos ensaios cl&#237;nicos considerados no presente estudo&#46;</p><p id="par0460" class="elsevierStylePara elsevierViewall">V&#225;rios aspetos metodol&#243;gicos podem justificar estas diferen&#231;as&#58; 1&#41; diferen&#231;as na modeliza&#231;&#227;o&#59; 2&#41; utiliza&#231;&#227;o de diferentes taxas de descontinua&#231;&#227;o por outras causas&#59; 3&#41; modeliza&#231;&#227;o da mortalidade ap&#243;s o per&#237;odo do ensaio&#59; 4&#41; utiliza&#231;&#227;o de diferentes valores de utilidade associados a cada est&#225;dio &#40;no presente estudo foram estimados com base em Sullivan et al&#46; em 2011<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">30</span></a>&#44; enquanto nos outros estudos foram utilizados os valores reportados pelo mesmo autor em 2006<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">46</span></a>&#41;&#59; 5&#41; taxas de atualiza&#231;&#227;o diferentes&#46;</p><p id="par0465" class="elsevierStylePara elsevierViewall">Todas as diferen&#231;as referidas anteriormente&#44; &#224; exce&#231;&#227;o da primeira&#44; foram alvo da an&#225;lise de sensibilidade univariada&#44; a qual confirmou a robustez dos resultados de base obtidos neste estudo&#46; Logo&#44; n&#227;o &#233; por via de qualquer um destes par&#226;metros que se podem explicar as diferen&#231;as nos resultados&#46; Fica a hip&#243;tese de as diferen&#231;as entre os estudos assentarem em modeliza&#231;&#245;es distintas&#46;</p><p id="par0470" class="elsevierStylePara elsevierViewall">As diferen&#231;as na modeliza&#231;&#227;o abarcam v&#225;rias dimens&#245;es&#44; incluindo a especifica&#231;&#227;o de diferentes est&#225;dios nos modelos Markov&#44; diferente dura&#231;&#227;o dos ciclos e a especifica&#231;&#227;o de apenas um n&#237;vel de gravidade para os AVC isqu&#233;micos ou hemorr&#225;gicos&#46; Outras diferen&#231;as nos estudos podem ter origem nos custos&#46; As estimativas destes s&#227;o influenciadas pelos recursos e especificidades dos cuidados de sa&#250;de de cada pa&#237;s&#44; bem como por eventuais diferen&#231;as internacionais nos pre&#231;os dos medicamentos&#46; Averiguar quantitativamente estas quest&#245;es fica para l&#225; do &#226;mbito do presente estudo&#46;</p><p id="par0475" class="elsevierStylePara elsevierViewall">Alguns estudos sugerem que o custo&#8208;efetividade dos NOAC est&#225; dependente do n&#237;vel de controlo da hipocoagula&#231;&#227;o&#44; sendo que estas interven&#231;&#245;es tender&#227;o a ser mais custo&#8208;efetivas num contexto de pior controlo de hipocoagula&#231;&#227;o&#46; Em particular&#44; foi estimado que a efetividade de dabigatrano ser&#225; menor em doentes que se encontram bem controlados<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">47&#44;48</span></a>&#46; No entanto&#44; nas an&#225;lises de sensibilidade realizadas para este par&#226;metro&#44; os resultados n&#227;o se alteraram marcadamente&#46;</p><p id="par0480" class="elsevierStylePara elsevierViewall">Este estudo apresenta algumas limita&#231;&#245;es ao n&#237;vel dos dados utilizados&#44; particularmente os relativos ao n&#250;mero de eventos&#44; uma vez que estes foram retirados de ensaios cl&#237;nicos com tempos de seguimento curtos &#40;2&#8208;3 anos&#41; e podem n&#227;o refletir os resultados reais de efetividade de cada anticoagulante&#46; Al&#233;m disso&#44; na aus&#234;ncia de compara&#231;&#245;es <span class="elsevierStyleItalic">head&#8208;to&#8208;head</span> entre os NOAC&#44; as efetividades foram estimadas de forma indireta&#44; utilizando a varfarina como comparador comum&#44; n&#227;o possibilitando&#44; deste modo&#44; o controlo das diferen&#231;as nas caracter&#237;sticas de base do doente&#44; no desenho do ensaio cl&#237;nico&#44; no n&#237;vel de adequabilidade do controlo da hipocoagula&#231;&#227;o&#44; ou nos perfis de risco determinados pelo <span class="elsevierStyleItalic">score</span> CHADS<span class="elsevierStyleInf">2</span> &#40;apesar de se ter verificado que os resultados de efetividade do apixabano s&#227;o consistentes na sub&#8208;popula&#231;&#227;o com valores m&#233;dios mais elevados de CHADS<span class="elsevierStyleInf">2</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">49</span></a>&#46; De acordo com a revis&#227;o da literatura realizada pelos autores&#44; as estimativas de efetividade utilizadas no estudo s&#227;o consistentes com os resultados das v&#225;rias compara&#231;&#245;es indiretas publicadas&#44; n&#227;o se tendo verificado altera&#231;&#245;es nos resultados quando se consideraram outras estimativas de efetividade obtidas por m&#233;todos <span class="elsevierStyleItalic">bayesianos</span><a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a>&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conclus&#227;o</span><p id="par0485" class="elsevierStylePara elsevierViewall">Nesta an&#225;lise de custo&#8208;efetividade&#44; baseada em compara&#231;&#245;es indiretas&#44; o apixabano revelou&#8208;se custo&#8208;efetivo <span class="elsevierStyleItalic">versus</span> a varfarina e dabigatrano&#44; e dominante <span class="elsevierStyleItalic">versus</span> rivaroxabano&#44; em doentes com FA n&#227;o&#8208;valvular&#46; Estes resultados foram robustos em todas as an&#225;lises de sensibilidade realizadas&#46; Esta informa&#231;&#227;o &#233; relevante para os diferentes decisores em sa&#250;de&#44; de forma a justificar a escolha da op&#231;&#227;o terap&#234;utica mais adequada perante o doente individual&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Responsabilidades &#233;ticas</span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Prote&#231;&#227;o de pessoas e animais</span><p id="par0490" class="elsevierStylePara elsevierViewall">Os autores declaram que para esta investiga&#231;&#227;o n&#227;o se realizaram experi&#234;ncias em seres humanos e&#47;ou animais&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Confidencialidade dos dados</span><p id="par0495" class="elsevierStylePara elsevierViewall">Os autores declaram que n&#227;o aparecem dados de pacientes neste artigo&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Direito &#224; privacidade e consentimento escrito</span><p id="par0500" class="elsevierStylePara elsevierViewall">Os autores declaram que n&#227;o aparecem dados de pacientes neste artigo&#46;</p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Financiamento</span><p id="par0505" class="elsevierStylePara elsevierViewall">Este estudo foi financiado pela Bristol&#8208;Myers Squibb Farmac&#234;utica Portuguesa&#44; SA e pelos Laborat&#243;rios Pfizer Lda&#46; O financiamento foi concedido independentemente dos resultados a obter&#46; M&#243;nica In&#234;s &#233; colaboradora dos Laborat&#243;rios Pfizer Lda&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conflito de interesses</span><p id="par0510" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflito de interesses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introdu&#231;&#227;o e objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Os <span class="elsevierStyleItalic">non&#8208;vitamin K antagonist oral anticoagulants</span> &#40;NOAC&#41; foram recentemente comparticipados para a fibrilha&#231;&#227;o auricular n&#227;o&#8208;valvular &#40;FA&#41;&#44; sendo relevante determinar o seu custo&#8208;efetividade para a realidade portuguesa&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Foi especificado um modelo Markov para simular a progress&#227;o dos doentes com FA no decurso da sua vida&#46; Os dados de efetividade relativa para os eventos acidente vascular cerebral &#40;isqu&#233;mico e hemorr&#225;gico&#41;&#44; hemorragia &#40;intracraniana&#44; outras hemorragias <span class="elsevierStyleItalic">majo</span>r e hemorragias <span class="elsevierStyleItalic">n&#227;o&#8208;major</span> clinicamente relevantes&#41;&#44; enfarte agudo do mioc&#225;rdio e descontinua&#231;&#227;o do tratamento foram obtidos por compara&#231;&#245;es indiretas entre o apixabano&#44; o dabigatrano e o rivaroxabano &#40;comparador comum&#58; varfarina&#41;&#46; As fontes dos dados de consumo de recursos de sa&#250;de foram a base de dados dos grupos de diagn&#243;stico homog&#233;neo e painel de peritos&#46; Estimou&#8208;se os anos de vida ganhos&#44; anos de vida ajustados pela qualidade &#40;QALY&#41;&#44; custos diretos e r&#225;cios de custo&#8208;efetividade incremental &#40;ICER&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Os anos de vida ganhos e os QALY foram maiores com apixabano&#44; com um ICER <span class="elsevierStyleItalic">versus</span> varfarina e dabigatrano de 5529<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY e 9163<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#44; respetivamente&#46; O apixabano foi dominante <span class="elsevierStyleItalic">versus</span> o rivaroxabano &#40;maiores ganhos em sa&#250;de e menores custos&#41;&#46; Estes resultados foram robustos nas an&#225;lises de sensibilidade realizadas&#44; tendo o apixabano uma probabilidade de 70&#37; de ser custo&#8208;efetivo &#40;<span class="elsevierStyleItalic">threshold</span>&#58; 20<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#41; <span class="elsevierStyleItalic">versus</span> o conjunto das restantes op&#231;&#245;es terap&#234;uticas&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclus&#245;es</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A utiliza&#231;&#227;o de apixabano em doentes com FA na pr&#225;tica cl&#237;nica portuguesa &#233; custo&#8208;efetiva <span class="elsevierStyleItalic">versus</span> varfarina e dabigatrano e dominante <span class="elsevierStyleItalic">versus</span> rivaroxabano na perspetiva do SNS&#46; Estas conclus&#245;es baseiam&#8208;se em compara&#231;&#245;es indiretas&#46; Apesar desta limita&#231;&#227;o&#44; esta informa&#231;&#227;o &#233; relevante para os diferentes decisores em sa&#250;de&#46;</p></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction and Objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Recently&#44; three novel non&#8208;vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non&#8208;valvular atrial fibrillation &#40;AF&#41;&#46; It is therefore important to evaluate the relative cost&#8208;effectiveness of these new oral anticoagulants in Portuguese AF patients&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0175" class="elsevierStyleSimplePara elsevierViewall">A Markov model was used to analyze disease progression over a lifetime horizon&#46; Relative efficacy data for stroke &#40;ischemic and hemorrhagic&#41;&#44; bleeding &#40;intracranial&#44; other major bleeding and clinically relevant non&#8208;major bleeding&#41;&#44; myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban&#44; dabigatran and rivaroxaban using warfarin as a common comparator&#46; Data on resource use were obtained from the database of diagnosis&#8208;related groups and an expert panel&#46; Model outputs included life years gained&#44; quality&#8208;adjusted life years &#40;QALYs&#41;&#44; direct healthcare costs and incremental cost&#8208;effectiveness ratios &#40;ICERs&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0180" class="elsevierStyleSimplePara elsevierViewall">Apixaban provided the most life years gained and QALYs&#46; The ICERs of apixaban compared to warfarin and dabigatran were &#8364;5529&#47;QALY and &#8364;9163&#47;QALY&#44; respectively&#46; Apixaban was dominant over rivaroxaban &#40;greater health gains and lower costs&#41;&#46; The results were robust over a wide range of inputs in sensitivity analyses&#46; Apixaban had a 70&#37; probability of being cost&#8208;effective &#40;at a threshold of &#8364;20 000&#47;QALY&#41; compared to all the other therapeutic options&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0185" class="elsevierStyleSimplePara elsevierViewall">Apixaban is a cost&#8208;effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system&#46; These conclusions are based on indirect comparisons&#44; but despite this limitation&#44; the information is useful for healthcare decision&#8208;makers&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introduction and Objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
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          0 => array:4 [
            "apendice" => "<p id="par0525" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Material suplement&#225;rio"
            "identificador" => "sec0130"
          ]
        ]
      ]
    ]
    "nomenclatura" => array:1 [
      0 => array:3 [
        "identificador" => "nom0005"
        "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0065">Gloss&#225;rio de abreviaturas</span>"
        "listaDefinicion" => array:2 [
          0 => array:1 [
            "definicion" => array:29 [
              0 => array:2 [
                "termino" => "95&#37; IC"
                "descripcion" => "<p id="par0005" class="elsevierStylePara elsevierViewall">Intervalo de Confian&#231;a a 95&#37;</p>"
              ]
              1 => array:2 [
                "termino" => "AVC"
                "descripcion" => "<p id="par0010" class="elsevierStylePara elsevierViewall">Acidente Vascular Cerebral</p>"
              ]
              2 => array:2 [
                "termino" => "CHLC"
                "descripcion" => "<p id="par0015" class="elsevierStylePara elsevierViewall">Centro Hospitalar Lisboa Central&#44; EPE</p>"
              ]
              3 => array:2 [
                "termino" => "cTTR"
                "descripcion" => "<p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Center&#39;s median time in therapeutic range</span></p>"
              ]
              4 => array:2 [
                "termino" => "CV"
                "descripcion" => "<p id="par0025" class="elsevierStylePara elsevierViewall">Cardiovascular</p>"
              ]
              5 => array:2 [
                "termino" => "EAM"
                "descripcion" => "<p id="par0030" class="elsevierStylePara elsevierViewall">Enfarte Agudo do Mioc&#225;rdio</p>"
              ]
              6 => array:2 [
                "termino" => "ES"
                "descripcion" => "<p id="par0035" class="elsevierStylePara elsevierViewall">Embolismo Sist&#233;mico</p>"
              ]
              7 => array:2 [
                "termino" => "FA"
                "descripcion" => "<p id="par0040" class="elsevierStylePara elsevierViewall">Fibrilha&#231;&#227;o Auricular n&#227;o&#8208;valvular</p>"
              ]
              8 => array:2 [
                "termino" => "GDHs"
                "descripcion" => "<p id="par0045" class="elsevierStylePara elsevierViewall">Grupos de Diagn&#243;stico Homog&#233;neos</p>"
              ]
              9 => array:2 [
                "termino" => "GI"
                "descripcion" => "<p id="par0050" class="elsevierStylePara elsevierViewall">Gastrointestinal</p>"
              ]
              10 => array:2 [
                "termino" => "HCR&#40;NM&#41;"
                "descripcion" => "<p id="par0055" class="elsevierStylePara elsevierViewall">Hemorragias Clinicamente Relevantes &#40;N&#227;o&#8208;<span class="elsevierStyleItalic">Major</span>&#41;</p>"
              ]
              11 => array:2 [
                "termino" => "HFF"
                "descripcion" => "<p id="par0060" class="elsevierStylePara elsevierViewall">Hospital Fernando da Fonseca&#44; EPE</p>"
              ]
              12 => array:2 [
                "termino" => "HIC"
                "descripcion" => "<p id="par0065" class="elsevierStylePara elsevierViewall">Hemorragia Intracraniana</p>"
              ]
              13 => array:2 [
                "termino" => "HM"
                "descripcion" => "<p id="par0070" class="elsevierStylePara elsevierViewall">Hemorragias <span class="elsevierStyleItalic">Major</span></p>"
              ]
              14 => array:2 [
                "termino" => "HR"
                "descripcion" => "<p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Hazard Ratio</span></p>"
              ]
              15 => array:2 [
                "termino" => "IC"
                "descripcion" => "<p id="par0080" class="elsevierStylePara elsevierViewall">Intracraniana</p>"
              ]
              16 => array:2 [
                "termino" => "ICER"
                "descripcion" => "<p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Incremental cost&#8208;effectiveness ratio</span></p>"
              ]
              17 => array:2 [
                "termino" => "INE"
                "descripcion" => "<p id="par0090" class="elsevierStylePara elsevierViewall">Instituto Nacional de Estat&#237;stica</p>"
              ]
              18 => array:2 [
                "termino" => "INR"
                "descripcion" => "<p id="par0095" class="elsevierStylePara elsevierViewall">R&#225;cio normalizado internacional &#8208; <span class="elsevierStyleItalic">International normalized ratio</span></p>"
              ]
              19 => array:2 [
                "termino" => "ITC"
                "descripcion" => "<p id="par0100" class="elsevierStylePara elsevierViewall">Compara&#231;&#227;o indireta frequencista &#8208; <span class="elsevierStyleItalic">Indirect treatment comparison</span></p>"
              ]
              20 => array:2 [
                "termino" => "MCDTs"
                "descripcion" => "<p id="par0105" class="elsevierStylePara elsevierViewall">Meios complementares de diagn&#243;stico e terap&#234;utica</p>"
              ]
              21 => array:2 [
                "termino" => "mRS"
                "descripcion" => "<p id="par0110" class="elsevierStylePara elsevierViewall">Escala Rankin modificada</p>"
              ]
              22 => array:2 [
                "termino" => "NMA"
                "descripcion" => "<p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Network Meta&#8208;Analysis</span></p>"
              ]
              23 => array:2 [
                "termino" => "NOACS"
                "descripcion" => "<p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Non&#8208;Vitamin K Antagonist Oral Anticoagulants</span></p>"
              ]
              24 => array:2 [
                "termino" => "OR"
                "descripcion" => "<p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Odds Ratio</span></p>"
              ]
              25 => array:2 [
                "termino" => "PTAT"
                "descripcion" => "<p id="par0130" class="elsevierStylePara elsevierViewall">Propor&#231;&#227;o de Tempo no Alvo Terap&#234;utico</p>"
              ]
              26 => array:2 [
                "termino" => "QALYs"
                "descripcion" => "<p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Quality&#8208;Adjusted Life Years</span></p>"
              ]
              27 => array:2 [
                "termino" => "RR"
                "descripcion" => "<p id="par0140" class="elsevierStylePara elsevierViewall">Risco Relativo</p>"
              ]
              28 => array:2 [
                "termino" => "SNS"
                "descripcion" => "<p id="par0145" class="elsevierStylePara elsevierViewall">Servi&#231;o Nacional de Sa&#250;de</p>"
              ]
            ]
          ]
          1 => array:2 [
            "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0070">List of Abbreviations</span>"
            "definicion" => array:29 [
              0 => array:2 [
                "termino" => "95&#37; CI"
                "descripcion" => "<p id="par0150" class="elsevierStylePara elsevierViewall">95&#37; Confidence Interval</p>"
              ]
              1 => array:2 [
                "termino" => "AVC"
                "descripcion" => "<p id="par0155" class="elsevierStylePara elsevierViewall">Stroke</p>"
              ]
              2 => array:2 [
                "termino" => "CHLC"
                "descripcion" => "<p id="par0160" class="elsevierStylePara elsevierViewall">Centro Hospitalar Lisboa Central&#44; EPE</p>"
              ]
              3 => array:2 [
                "termino" => "cTTR"
                "descripcion" => "<p id="par0165" class="elsevierStylePara elsevierViewall">Center&#39;s median time in therapeutic range</p>"
              ]
              4 => array:2 [
                "termino" => "CV"
                "descripcion" => "<p id="par0170" class="elsevierStylePara elsevierViewall">Cardiovascular</p>"
              ]
              5 => array:2 [
                "termino" => "EAM"
                "descripcion" => "<p id="par0175" class="elsevierStylePara elsevierViewall">Acute Myocardial Infarction</p>"
              ]
              6 => array:2 [
                "termino" => "ES"
                "descripcion" => "<p id="par0180" class="elsevierStylePara elsevierViewall">Systemic Embolism</p>"
              ]
              7 => array:2 [
                "termino" => "FA"
                "descripcion" => "<p id="par0185" class="elsevierStylePara elsevierViewall">Non valvular atrial fibrillation</p>"
              ]
              8 => array:2 [
                "termino" => "GDHs"
                "descripcion" => "<p id="par0190" class="elsevierStylePara elsevierViewall">Diagnosis Related Groups</p>"
              ]
              9 => array:2 [
                "termino" => "GI"
                "descripcion" => "<p id="par0195" class="elsevierStylePara elsevierViewall">Gastrointestinal</p>"
              ]
              10 => array:2 [
                "termino" => "HCR&#40;NM&#41;"
                "descripcion" => "<p id="par0200" class="elsevierStylePara elsevierViewall">Clinically Relevant Non&#8208;Major Bleeding</p>"
              ]
              11 => array:2 [
                "termino" => "HFF"
                "descripcion" => "<p id="par0205" class="elsevierStylePara elsevierViewall">Hospital Fernando da Fonseca&#44; EPE</p>"
              ]
              12 => array:2 [
                "termino" => "HIC"
                "descripcion" => "<p id="par0210" class="elsevierStylePara elsevierViewall">Intracranial Bleeding</p>"
              ]
              13 => array:2 [
                "termino" => "HM"
                "descripcion" => "<p id="par0215" class="elsevierStylePara elsevierViewall">Major Bleeding</p>"
              ]
              14 => array:2 [
                "termino" => "HR"
                "descripcion" => "<p id="par0220" class="elsevierStylePara elsevierViewall">Hazard Ratio</p>"
              ]
              15 => array:2 [
                "termino" => "IC"
                "descripcion" => "<p id="par0225" class="elsevierStylePara elsevierViewall">Intracranial</p>"
              ]
              16 => array:2 [
                "termino" => "ICER"
                "descripcion" => "<p id="par0230" class="elsevierStylePara elsevierViewall">Incremental cost&#8208;effectiveness ratio</p>"
              ]
              17 => array:2 [
                "termino" => "INE"
                "descripcion" => "<p id="par0235" class="elsevierStylePara elsevierViewall">National Institute of Statistics</p>"
              ]
              18 => array:2 [
                "termino" => "INR"
                "descripcion" => "<p id="par0240" class="elsevierStylePara elsevierViewall">International normalized ratio</p>"
              ]
              19 => array:2 [
                "termino" => "ITC"
                "descripcion" => "<p id="par0245" class="elsevierStylePara elsevierViewall">Indirect Treatment Comparison</p>"
              ]
              20 => array:2 [
                "termino" => "MCDTs"
                "descripcion" => "<p id="par0250" class="elsevierStylePara elsevierViewall">Complementary means of diagnosis and therapeutic</p>"
              ]
              21 => array:2 [
                "termino" => "mRS"
                "descripcion" => "<p id="par0255" class="elsevierStylePara elsevierViewall">Modified Rankin scale</p>"
              ]
              22 => array:2 [
                "termino" => "NMA"
                "descripcion" => "<p id="par0260" class="elsevierStylePara elsevierViewall">Network Meta&#8208;Analysis</p>"
              ]
              23 => array:2 [
                "termino" => "NOACS"
                "descripcion" => "<p id="par0265" class="elsevierStylePara elsevierViewall">Non&#8208;Vitamin K Antagonist Oral Anticoagulants</p>"
              ]
              24 => array:2 [
                "termino" => "OR"
                "descripcion" => "<p id="par0270" class="elsevierStylePara elsevierViewall">Odds Ratio</p>"
              ]
              25 => array:2 [
                "termino" => "PTAT"
                "descripcion" => "<p id="par0275" class="elsevierStylePara elsevierViewall">Time proportion within therapeutic range</p>"
              ]
              26 => array:2 [
                "termino" => "QALYs"
                "descripcion" => "<p id="par0280" class="elsevierStylePara elsevierViewall">Quality&#8208;Adjusted Life Years</p>"
              ]
              27 => array:2 [
                "termino" => "RR"
                "descripcion" => "<p id="par0285" class="elsevierStylePara elsevierViewall">Relative Risk</p>"
              ]
              28 => array:2 [
                "termino" => "SNS"
                "descripcion" => "<p id="par0290" class="elsevierStylePara elsevierViewall">National Health Service</p>"
              ]
            ]
          ]
        ]
      ]
    ]
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Modelo de Markov&#58; &#225;rvore de decis&#227;o&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">AC&#58; anticoagulantes&#59; AVC&#58; acidente vascular cerebral&#59; EAM&#58; enfarte agudo do mioc&#225;rdio&#59; ES&#58; embolismo sist&#233;mico&#59; FANV&#58; fibrilha&#231;&#227;o auricular n&#227;o valvular&#59; FANV sem AC&#58; fibrilha&#231;&#227;o auricular n&#227;o valvular&#59; HCR &#40;NM&#41;&#58; hemorragias clinicamente relevantes &#40;n&#227;o&#8208;<span class="elsevierStyleItalic">major</span>&#41;&#59; HIC&#58; hemorragia intracraniana&#46; Reproduzido de Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a>&#46;</p>"
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Estimativas de efetividade do apixabano <span class="elsevierStyleItalic">versus</span> outros NOAC nas compara&#231;&#245;es indiretas publicadas&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A&#58; apixabano&#59; B&#58; meta&#8208;an&#225;lise em rede bayesiana&#59; D&#58; dabigatrano&#59; ITC&#58; compara&#231;&#227;o indireta frequencista&#59; R&#58; rivaroxabano&#46; &#42;O estudo RE&#8208;LY apresenta apenas resultados para hemoragias <span class="elsevierStyleItalic">minor</span>&#44; que foram utilizadas como <span class="elsevierStyleItalic">proxy</span> de hemorragias clinicamente relevantes &#40;n&#227;o&#8208;<span class="elsevierStyleItalic">major</span>&#41;&#46;</p>"
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          "pt" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Estrutura do custo total m&#233;dio por doente com cada op&#231;&#227;o terap&#234;utica no horizonte temporal coincidente com o tempo de vida &#40;<span class="elsevierStyleItalic">lifetime</span>&#41;&#46;</p>"
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          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Efetividade &#40;QALY&#41; e custos incrementais dos NOAC relativamente &#224; varfarina&#46;</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">NOAC&#58; non&#8208;vitamin K antagonist oral anticoagulants&#59; QALY&#58; quality&#8208;adjusted life years&#59; ICER&#58; incremental cost&#8208;effectiveness <span class="elsevierStyleItalic">ratio</span>&#46;</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Este gr&#225;fico compara a efetividade &#40;QALY&#41; e os custos incrementais dos NOAC relativamente &#224; varfarina &#40;representada na coordenada 0&#44;0&#41;&#46; A linha vermelha representa a fronteira de custo&#8208;efetividade&#46; A sua inclina&#231;&#227;o em cada segmento corresponde ao ICER entre os pontos definindo esse segmento&#46; Os NOAC com menos QALY incrementais localizam&#8208;se mais &#224; esquerda e os NOAC com maiores custos incrementais localizam&#8208;se mais acima&#46; O apixabano constitui uma op&#231;&#227;o terap&#234;utica com custos incrementais de 1064<span class="elsevierStyleHsp" style=""></span>&#8364; face aos da varfarina&#44; mas apresenta a maior efetividade comparativamente a todas as alternativas terap&#234;uticas&#46; Os pontos &#224; esquerda da linha s&#227;o dominados por combina&#231;&#245;es de terap&#234;uticas mais efectivas que na fronteira&#46; Neste caso&#44; o rivaroxabano &#233; estritamente dominado pelo apixabano&#44; apresentando menos QALY e mais custos&#46;</p>"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Curvas de aceitabilidade&#46;</p> <p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Este gr&#225;fico refere&#8208;se &#224; curva de aceitabilidade&#44; onde para cada valor da disposi&#231;&#227;o a pagar se mostra a percentagem das simula&#231;&#245;es que s&#227;o custo&#8208;efetivas para cada tratamento&#44; permitindo uma compara&#231;&#227;o simult&#226;nea entre todas as op&#231;&#245;es terap&#234;uticas&#46; O apixabano &#233; a melhor alternativa a partir dos 8000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#46; Para uma disposi&#231;&#227;o a pagar de 20<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;QALY&#44; a probabilidade do apixabano ser custo&#8208;efetivo face ao conjunto de todas as alternativas &#233; de 70&#37;&#46;</p>"
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">HR&#58; <span class="elsevierStyleItalic">hazard ratio</span>&#59; OR&#58; <span class="elsevierStyleItalic">odds ratio</span>&#59; RR&#58; risco relativo&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estudos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Medida de associa&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ensaios cl&#237;nicos inclu&#237;dos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Compara&#231;&#245;es indiretas frequencistas</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a>&#44; 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">HR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Testa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">17</span></a>&#44; 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Harenberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">16</span></a>&#44; 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Baker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">15</span></a>&#44; 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&#44; PETRO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">18</span></a>&#44; 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">HR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Meta&#8208;an&#225;lise em rede &#40;bayesiano&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mitchell et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">20</span></a>&#44; 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">HR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Assiri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">22</span></a>&#44; 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&#44; 18 outros RCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dogliotti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">6</span></a>&#44; 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&#44; AVERROES&#44; ACTIVE&#8208;W&#44; ACTIVE&#8208;A11 compara&#231;&#245;es <span class="elsevierStyleItalic">versus</span> placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cameron et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">21</span></a>&#44; 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RE&#8208;LY&#44; ROCKET AF&#44; ARISTOTLE&#44; ARISTOTLE J&#44; ENGAGE AFAVERROES&#44; ACTIVE&#8208;W&#44; ACTIVE&#8208;Acompara&#231;&#245;es <span class="elsevierStyleItalic">versus</span> placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab965788.png"
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          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas das compara&#231;&#245;es indiretas publicadas entre os NOAC na FA</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apixabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Varfarina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dabigatrano 110<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dabigatrano 150<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rivaroxabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AVC isqu&#233;mico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;09 &#40;0&#44;89&#59; 1&#44;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;20 &#40;0&#44;88&#59; 1&#44;64&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;82 &#40;0&#44;60&#59; 1&#44;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;98 &#40;0&#44;72&#59; 1&#44;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemorragia intracraniana<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;38 &#40;1&#44;72&#59; 3&#44;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;73 &#40;0&#44;43&#59; 1&#44;26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;02 &#40;0&#44;62&#59; 1&#44;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;73 &#40;1&#44;08&#59; 2&#44;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ES&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Outras hemorragias <span class="elsevierStyleItalic">major</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;27 &#40;1&#44;08&#59; 1&#44;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;21 &#40;0&#44;97&#59; 1&#44;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;37 &#40;1&#44;10&#59; 1&#44;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;44 &#40;1&#44;15&#59; 1&#44;79&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemorragias clinicamente relevantes &#40;n&#227;o&#8208;<span class="elsevierStyleItalic">major</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;43 &#40;1&#44;24&#59; 1&#44;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;16 &#40;0&#44;99&#59; 1&#44;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;30 &#40;1&#44;11&#59; 1&#44;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;49 &#40;1&#44;26&#59; 1&#44;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;14 &#40;0&#44;86&#59; 1&#44;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;47 &#40;0&#44;96&#59; 2&#44;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;46 &#40;0&#44;95&#59; 2&#44;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;94 &#40;0&#44;64&#59; 1&#44;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Outras hospitaliza&#231;&#245;es CV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;00 &#40;0&#44;90&#59; 1&#44;10&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">A hemorragia intracraniana inclui o AVC hemorr&#225;gico e outros tipos de hemorragias intracranianas&#46; A propor&#231;&#227;o de AVC hemorr&#225;gico foi de 77&#44; 64&#44; 64&#44; 41 e 57&#37; para apixabano&#44; varfarina&#44; dabigatrano 110<span class="elsevierStyleHsp" style=""></span>mg&#44; dabigatrano 150<span class="elsevierStyleHsp" style=""></span>mg e rivaroxabano&#44; respetivamente&#44; de acordo com a literatura &#40;an&#225;lise secund&#225;ria do estudo ARISTOTLE&#59; RE&#8208;LY&#59; ROCKET AF&#41;&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Pressuposto&#44; dada a reduzida taxa de eventos de ES nos ensaios&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Assume&#8208;se igual &#224; apixabano&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">AVC&#58; acidente vascular cerebral&#59; EAM&#58; enfarte agudo do mioc&#225;rdio&#59; ES&#58; embolismo sist&#233;mico&#46;</p> <p class="elsevierStyleNotepara" id="npar0025">Fonte&#58; Lip et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">10</span></a>&#44; 2014&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Hazard ratios</span> &#40;IC 95&#37;&#41;&#58; apixabano <span class="elsevierStyleItalic">versus</span> varfarina e outros NOAC</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 8"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">AVC&#58; acidente vascular cerebral&#59; CHLC&#58; Centro Hospitalar Lisboa Central&#44; EPE&#59; EAM&#58; enfarte agudo do mioc&#225;rdio&#59; ES&#58; embolismo sist&#233;mico&#59; IC&#58; intracranianas&#59; GI&#58; gastrointestinais&#59; HFF&#58; Hospital Fernando da Fonseca&#44; EPE&#46;</p><p id="spar0190" class="elsevierStyleSimplePara elsevierViewall">Fonte&#58; <span class="elsevierStyleSup">a</span> base de dados CHLC e HFF&#59; <span class="elsevierStyleSup">b</span> Portaria GDH 20&#47;2014<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">24</span></a>&#59; <span class="elsevierStyleSup">c</span> painel de peritos&#46;</p>"
          "tablatextoimagen" => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Custos</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Eventos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Agudos &#40;por epis&#243;dio&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Longo prazo &#40;por m&#234;s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AVC isqu&#233;mico n&#227;o fatal &#40;m&#233;dia ponderada&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8653&#44;26<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&#44;57<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AVC isqu&#233;mico fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6381&#44;20<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AVC hemorr&#225;gico n&#227;o fatal &#40;m&#233;dia ponderada&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13<span class="elsevierStyleHsp" style=""></span>779&#44;62<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41&#44;07<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AVC hemorr&#225;gico fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10<span class="elsevierStyleHsp" style=""></span>419&#44;64<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Outras hemorragias intracranianas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7932&#44;21<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemorragias GI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2798&#44;64<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemorragias n&#227;o&#8208;IC e n&#227;o&#8208;GI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2090&#44;04<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemorragias clinicamente relevantes n&#227;o&#8208;<span class="elsevierStyleItalic">major</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2514&#44;98<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#44;32<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ES&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3937&#44;93<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4560&#44;10<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#44;61<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Outros internamentos por evento cardiovascular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2081&#44;64<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Consulta de rotina&#47;monitoriza&#231;&#227;o</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Medica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Custo m&#233;dio di&#225;rio<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequ&#234;ncia mensal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Valor<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Varfarina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;08<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;92<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#44;00<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Apixabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;41<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;33<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#44;00<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dabigatrano 110<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;36<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;33<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#44;00<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dabigatrano 150<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;46<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;33<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#44;00<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rivaroxabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#44;47<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;33<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#44;00<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Os pre&#231;os dos medicamentos foram valorizados sem IVA&#46;</p>"
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          "pt" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Custos gerados pela ocorr&#234;ncia dos eventos vasculares&#44; terap&#234;utica anticoagulante e consultas de rotina&#47;monitoriza&#231;&#227;o</p>"
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          "leyenda" => "<p id="spar0140" class="elsevierStyleSimplePara elsevierViewall">AVC&#58; acidente vascular cerebral&#59; CV&#58; cardiovascular&#59; EAM&#58; enfarte agudo do mioc&#225;rdio&#59; ES&#58; embolismo sist&#233;mico&#59; FA&#58; fibrilha&#231;&#227;o auricular&#59; NOAC&#58; <span class="elsevierStyleItalic">non&#8208;vitamin K antagonist oral anticoagulants&#46;</span></p><p id="spar0195" class="elsevierStyleSimplePara elsevierViewall">Fonte&#58; <span class="elsevierStyleSup">a</span> Sullivan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">30</span></a>&#44; 2011&#59; <span class="elsevierStyleSup">b</span> Gage et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">31</span></a>&#44; 2006&#46;</p>"
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="char" valign="top"><span class="elsevierStyleBold">Utilidade considerada no modelo para cada estadio da doen&#231;a</span><span class="elsevierStyleSup">a</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FA &#40;utilidade de base&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;7270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">AVC &#40;isqu&#233;micos e hemorr&#225;gicos&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ligeiro&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;6151&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Moderado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;5646&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;5142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ES</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;6265&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">EAM</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;6098&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Decremento da utilidade associado &#224; terap&#234;utica com anticoagulantes e &#224; ocorr&#234;ncia de outros eventos vasculares &#40;dura&#231;&#227;o&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Anticoagulantes</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Varfarina<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;0130<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NOAC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;0000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Eventos</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Outras hemorragias intracranianas &#40;excluindo AVC hemorr&#225;gico&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;1511 &#40;seis semanas&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Outras hemorragias <span class="elsevierStyleItalic">major</span> &#40;excluindo hemorragias intracranianas&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;1511 &#40;14 dias&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hemorragias n&#227;o&#8208;<span class="elsevierStyleItalic">major</span> clinicamente relevantes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;0582 &#40;dois dias&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Outros internamentos CV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;1276 &#40;seis dias&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0155" class="elsevierStyleSimplePara elsevierViewall">AVC&#58; acidente vascular cerebral&#59; CV&#58; cardiovascular&#59; EAM&#58; enfarte agudo do mioc&#225;rdio&#59; ES&#58; embolismo sist&#233;mico&#59; IC&#58; intracranianas&#59; GI&#58; gastrointestinais&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#250;mero de eventos &#40;popula&#231;&#227;o total&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apixabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Varfarina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dabigatrano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rivaroxabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">AVC isqu&#233;mico</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19<span class="elsevierStyleHsp" style=""></span>799&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20<span class="elsevierStyleHsp" style=""></span>703&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20<span class="elsevierStyleHsp" style=""></span>066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19<span class="elsevierStyleHsp" style=""></span>649&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2932&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2857&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3392&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3283&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22<span class="elsevierStyleHsp" style=""></span>731&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23<span class="elsevierStyleHsp" style=""></span>560&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23<span class="elsevierStyleHsp" style=""></span>458&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22<span class="elsevierStyleHsp" style=""></span>931&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">AVC hemorr&#225;gico</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1602&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2040&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">996&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1879&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">702&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">938&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2609&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4212&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1698&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2818&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">ES</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2175&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2403&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2263&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">221&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">225&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">249&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2359&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2652&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2497&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Outras hemorragias IC</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1063&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2255&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1521&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1901&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">159&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">337&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">227&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">284&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1221&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2591&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1748&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Outras hemorragias major</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hemorragias n&#227;o fatais GI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5055&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5713&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7501&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8338&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hemorragias n&#227;o fatais n&#227;o&#8208; IC e n&#227;o GI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8137&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10<span class="elsevierStyleHsp" style=""></span>123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8984&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10<span class="elsevierStyleHsp" style=""></span>802&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">269&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">326&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">336&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">391&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13<span class="elsevierStyleHsp" style=""></span>461&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16<span class="elsevierStyleHsp" style=""></span>159&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16<span class="elsevierStyleHsp" style=""></span>822&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19<span class="elsevierStyleHsp" style=""></span>530&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hemorragias n&#227;o&#8208;<span class="elsevierStyleItalic">major</span> clinicamente relevantes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25<span class="elsevierStyleHsp" style=""></span>248&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30<span class="elsevierStyleHsp" style=""></span>700&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29<span class="elsevierStyleHsp" style=""></span>914&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33<span class="elsevierStyleHsp" style=""></span>367&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">EAM</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>N&#227;o fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7179&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8366&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7182&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fatal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1067&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1214&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1044&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8412&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9579&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8226&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Outras hospitaliza&#231;&#245;es CV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">116<span class="elsevierStyleHsp" style=""></span>048&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">112<span class="elsevierStyleHsp" style=""></span>390&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">117<span class="elsevierStyleHsp" style=""></span>558&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">116<span class="elsevierStyleHsp" style=""></span>738&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Outros motivos de descontinua&#231;&#227;o do tratamento</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63<span class="elsevierStyleHsp" style=""></span>406&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62<span class="elsevierStyleHsp" style=""></span>408&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72<span class="elsevierStyleHsp" style=""></span>720&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66<span class="elsevierStyleHsp" style=""></span>616&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">&#211;bitos</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Relacionados com o evento cl&#237;nico &#40;agudo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5940&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7332&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6364&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6480&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Relacionados com o evento cl&#237;nico &#40;morte devida a AVC&#44; EAM&#44; embolismo sist&#233;mico&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30<span class="elsevierStyleHsp" style=""></span>524&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32<span class="elsevierStyleHsp" style=""></span>066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31<span class="elsevierStyleHsp" style=""></span>694&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30<span class="elsevierStyleHsp" style=""></span>779&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Outros&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63<span class="elsevierStyleHsp" style=""></span>536&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60<span class="elsevierStyleHsp" style=""></span>602&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61<span class="elsevierStyleHsp" style=""></span>942&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62<span class="elsevierStyleHsp" style=""></span>741&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Total</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab965789.png"
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0150" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero de eventos em cada op&#231;&#227;o terap&#234;utica &#40;taxa por 100<span class="elsevierStyleHsp" style=""></span>000 doentes&#41;</p>"
        ]
      ]
      10 => array:7 [
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        "etiqueta" => "Tabela 12"
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        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Varfarina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apixabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dabigatrano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rivaroxabano&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5467&#44;29<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4989&#44;03<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5244&#44;03<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5386&#44;30<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Terap&#234;utica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">214&#44;42<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3754&#44;35<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3015&#44;69<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3463&#44;96<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Monitoriza&#231;&#227;o e cuidados de rotina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3252&#44;29<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1254&#44;77<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1311&#44;27<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1278&#44;31<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8934&#44;16<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9998&#44;14<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9570&#44;99<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10<span class="elsevierStyleHsp" style=""></span>128&#44;56<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0160" class="elsevierStyleSimplePara elsevierViewall">Custo total m&#233;dio por doente&#44; com cada op&#231;&#227;o terap&#234;utica no horizonte temporal coincidente com o tempo de vida <span class="elsevierStyleItalic">&#40;lifetime&#41;</span></p>"
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          "leyenda" => "<p id="spar0170" class="elsevierStyleSimplePara elsevierViewall">ICER&#58; r&#225;cio de custo&#8208;efetividade incremental&#59; QALY&#58; quality&#8208;adjusted life years&#46;</p>"
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            0 => array:2 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Apixabano <span class="elsevierStyleItalic">versus</span></th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Varfarina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dabigatrano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rivaroxabano&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Custos incrementais</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">427&#44;15<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;130&#44;42<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Anos de vida ganhos</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">QALY incrementais</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">ICER</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Custo por ano de vida ganho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5708&#44;44<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7926&#44;91<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Custo por QALY ganho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5529&#44;05<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9162&#44;77<span class="elsevierStyleHsp" style=""></span>&#8364;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dominante&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab965790.png"
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          "pt" => "<p id="spar0165" class="elsevierStyleSimplePara elsevierViewall">Resultados de custo&#8208;efetividade no cen&#225;rio de base&#58; apixabano <span class="elsevierStyleItalic">versus</span> varfarina e outros NOAC</p>"
        ]
      ]
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        "Ecomponente" => array:2 [
          "fichero" => "mmc1.docx"
          "ficheroTamanyo" => 192191
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    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:49 [
            0 => array:3 [
              "identificador" => "bib0280"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of atrial fibrillation in the Portuguese population aged 40 and over&#58; the FAMA study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "D&#46; Bonhorst"
                            1 => "M&#46; Mendes"
                            2 => "P&#46; Adrag&#227;o"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Cardiol&#46;"
                        "fecha" => "2010"
                        "volumen" => "29"
                        "paginaInicial" => "331"
                        "paginaFinal" => "350"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20635561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A survey of atrial fibrillation in general practice&#58; the West Birmingham Atrial Fibrillation Project"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "G&#46;Y&#46; Lip"
                            1 => "D&#46;J&#46; Golding"
                            2 => "M&#46; Nazir"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Gen Pract&#46;"
                        "fecha" => "1997"
                        "volumen" => "47"
                        "paginaInicial" => "285"
                        "paginaFinal" => "289"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9219403"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            2 => array:3 [
              "identificador" => "bib0290"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increasing prevalence of atrial fibrillation and flutter in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "G&#46;V&#46; Naccarelli"
                            1 => "H&#46; Varker"
                            2 => "J&#46; Lin"
                          ]
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