Pentasaccharides para o tratamento da trombose venosa profunda
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Data
2016-05-25
Autores
Brandão, Gustavo Muçouçah Sampaio [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Pentasaccharides para o tratamento da trombose venosa profunda Questão da revisão: Os novos anticoagulantes da classe dos pentasaccharides podem ser uma alternativa eficaz e segura aos anticoagulantes convencionais utilizados na terapia padrão do tratamento da trombose venosa profunda? Visão geral: Trombose venosa profunda (TVP) é uma doença grave e potencialmente fatal que se caracteriza pela formação aguda de um coágulo de sangue nas veias profundas. Sua incidência aumenta exponencialmente com a idade e estima-se que na população geral, sua incidência seja de 5 casos em 10,000 habitantes. O tratamento padrão se faz por meio de medicamentos anticoagulantes, inicialmente pela administração de medicamentos injetáveis, as heparinas, por 5 a 7 dias e em seguida pelo uso prolongado de medicamentos de uso oral, os antagonistas da vitamina K. Entretanto, o alto risco de sangramento e a necessidade de um rigoroso controle laboratorial, permanecem como importantes limitações à terapia padrão. Os pentasaccharides são anticoagulantes sintéticos que podem apresentar vantagens em relação ao tratamento convencional como um efeito mais previsível, um regime de dosagem mais conveniente, a ausência da necessidade de controle laboratorial, ausência de interações com medicamentos e/ou alimentos, ausência da temida diminuição das plaquetas induzida pela heparina e em muitos casos melhor custo-benefício. Características chaves e resultados: Nossas buscas, realizadas até julho de 2015, identificaram 20 entre 730 registros que representavam 5 estudos elegíveis, compreendendo um total de 6981 pacientes. Os estudos compararam os pentasaccharides fondaparinux, idraparinux e idrabiotaparinux com a terapia padrão (heparina seguida por antagonista da vitamina K). O principal resultado de eficácia foi feito pela avaliação da incidência de qualquer episódio tromboembolismo venoso (novo episódio de TVP ou embolia pulmonar) durante o tratamento. E o principal resultado de danos foi incidência de sangramento. Esta revisão mostrou que os pentasaccharides (fondaparinux, e a dose de 2.5 mg de idraparinux e a dose equivalente de 3.0 mg de idrabiotaparinux) podem ser uma alternativa eficaz e segura a anticoagulação convencional para o tratamento da TVP. Qualidade da evidência: A qualidade da evidência foi considerada moderada a alta. Um único estudo incluído (Persist) poderia ser julgado potencialmente falho devido ao relevante número de pacientes que foram perdidos ou descontinuaram prematuramente o tratamento após a randomização. De forma geral, os estudos incluídos responderam diretamente as perguntas e foram considerados de boa qualidade. Os resultados dos estudos foram consistentes e os efeitos estimados foram precisos. Nós acreditamos que seja improvável que a maioria dos nossos principais resultados de eficácia e danos possam ser modificados por estudos adicionais. Entretanto, estudos futuros com os pentasaccharides de meia vida prolongada (idraparinux e idrabiotaparinux) em baixas doses podem confirmar nossas estimativas com relação a sua não inferioridade em comparação à terapia padrão.
Background: Deep vein thrombosis (DVT) is a severe disorder caused by acute formation of a clot or thrombus in the deep vein system. The incidence of DVT increases with age: from 2 to 3/10,000 in adults aged 30 to 49 years to 20/10,000 in adults aged 70 to 79 years. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Standard treatment is based on antithrombotic therapy, initially with parenteral administration of unfractionated heparin or low molecular weight heparins (LMWH) for five to seven days, then subsequent long-term oral vitamin K antagonists (e.g. warfarin) therapy. However, hemorrhagic complications are a major concern associated with warfarin treatment. Indeed, the hemorrhagic risk of warfarin and the required laboratory control remain the Achilles’ heel of vitamin K antagonist management. The pentasaccharides have characteristics that may be favourable over conventional treatment, including a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions and absence of heparin-induced thrombocytopenia. To date, no systematic review has measured the effectiveness and safety of these drugs in the treatment of DVT. Objectives: To assess the efficacy and harms of pentasaccharides for the treatment of deep venous thrombosis. Search strategy: 1 The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched July 2015) and the Cochrane Register of Studies (last searched July 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations. Selection criteria: We included randomised controlled trials in which people with a DVTconfirmed by standard imaging techniques, were allocated to receive a pentasaccharide (fondaparinux, idraparinux or idrabiotaparinux) for the treatment of DVT. Data collection and analysis: Three review authors (GB, DJ and MS) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion. We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and major (and clinically non-major) bleeding. Other outcomes included all-cause mortality, recurrent DVT, PE, thrombocytopenia, heparin-induced thrombocytopenia syndrome and all other adverse effects induced by the treatments . We calculated all outcomes using a relative risk (RR) with a 95% confidence interval (CI). Main results: We included 5 randomised controlled trials of 6981 participants. Two studies tested fondaparinux, while three tested idraparinux (being one tested idrabiotaparinux). We deemed all included studies to be of high methodological quality and generally low risk of bias. The quality of the evidence was generally graded as high as the outcomes were direct and effect estimates were consistent and precise, as reflected in the narrow CIs around the RRs. Meta-analysis of two studies (2658 participants) comparing fondaparinux with standard anticoagulation groups showed no difference in the risk of recurrent VTE (RR 0.88, 95% CI 0.60 to 1.29). The RR of bleeding in the initial period of treatment (RR 0.94, 95% CI 0.73 to 1.22) and three months of follow up (RR 0.61, 95% CI 0.36 to 1.01) were similar comparing both interventions. Two studies comparing idraparinux with standard therapy showed no difference in the risk of recurrent VTE during three months (RR 1.51; 95% CI 0.26, 8.90) and (RR 0.79; 95% CI 0.21; 2.91). The treatment with idraparinux clearly showed a bleeding risk with a pattern dose-response. However, at a dose of 2.5 mg idraparinux, there was no significant difference in the risk of bleeding in patients receiving idrapaparinux in comparison to standard therapy during six months of follow up (RR 0.92, 95% CI 0.69 to 1.22). One study contributed with data for the analysis (n=741 participants) that there was no significant difference in the risk of recurrent VTE during six months follow-up between idrabiotaparinux compared with idraparinux (RR 0.71, 95% CI 0.30 to 1.66). The risk of bleeding was also similar comparing the two interventions (RR 0.71, 95% CI 0.49 to 1.04). Authors' conclusions: The pentasaccharides (fondaparinux, the dose of 2.5 mg idraparinux and equimolar dose of 3.0 mg idrabiotaparinux) may be an effective and safe alternative to conventional anticoagulation treatment for acute DVT.
Background: Deep vein thrombosis (DVT) is a severe disorder caused by acute formation of a clot or thrombus in the deep vein system. The incidence of DVT increases with age: from 2 to 3/10,000 in adults aged 30 to 49 years to 20/10,000 in adults aged 70 to 79 years. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Standard treatment is based on antithrombotic therapy, initially with parenteral administration of unfractionated heparin or low molecular weight heparins (LMWH) for five to seven days, then subsequent long-term oral vitamin K antagonists (e.g. warfarin) therapy. However, hemorrhagic complications are a major concern associated with warfarin treatment. Indeed, the hemorrhagic risk of warfarin and the required laboratory control remain the Achilles’ heel of vitamin K antagonist management. The pentasaccharides have characteristics that may be favourable over conventional treatment, including a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions and absence of heparin-induced thrombocytopenia. To date, no systematic review has measured the effectiveness and safety of these drugs in the treatment of DVT. Objectives: To assess the efficacy and harms of pentasaccharides for the treatment of deep venous thrombosis. Search strategy: 1 The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched July 2015) and the Cochrane Register of Studies (last searched July 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations. Selection criteria: We included randomised controlled trials in which people with a DVTconfirmed by standard imaging techniques, were allocated to receive a pentasaccharide (fondaparinux, idraparinux or idrabiotaparinux) for the treatment of DVT. Data collection and analysis: Three review authors (GB, DJ and MS) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion. We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and major (and clinically non-major) bleeding. Other outcomes included all-cause mortality, recurrent DVT, PE, thrombocytopenia, heparin-induced thrombocytopenia syndrome and all other adverse effects induced by the treatments . We calculated all outcomes using a relative risk (RR) with a 95% confidence interval (CI). Main results: We included 5 randomised controlled trials of 6981 participants. Two studies tested fondaparinux, while three tested idraparinux (being one tested idrabiotaparinux). We deemed all included studies to be of high methodological quality and generally low risk of bias. The quality of the evidence was generally graded as high as the outcomes were direct and effect estimates were consistent and precise, as reflected in the narrow CIs around the RRs. Meta-analysis of two studies (2658 participants) comparing fondaparinux with standard anticoagulation groups showed no difference in the risk of recurrent VTE (RR 0.88, 95% CI 0.60 to 1.29). The RR of bleeding in the initial period of treatment (RR 0.94, 95% CI 0.73 to 1.22) and three months of follow up (RR 0.61, 95% CI 0.36 to 1.01) were similar comparing both interventions. Two studies comparing idraparinux with standard therapy showed no difference in the risk of recurrent VTE during three months (RR 1.51; 95% CI 0.26, 8.90) and (RR 0.79; 95% CI 0.21; 2.91). The treatment with idraparinux clearly showed a bleeding risk with a pattern dose-response. However, at a dose of 2.5 mg idraparinux, there was no significant difference in the risk of bleeding in patients receiving idrapaparinux in comparison to standard therapy during six months of follow up (RR 0.92, 95% CI 0.69 to 1.22). One study contributed with data for the analysis (n=741 participants) that there was no significant difference in the risk of recurrent VTE during six months follow-up between idrabiotaparinux compared with idraparinux (RR 0.71, 95% CI 0.30 to 1.66). The risk of bleeding was also similar comparing the two interventions (RR 0.71, 95% CI 0.49 to 1.04). Authors' conclusions: The pentasaccharides (fondaparinux, the dose of 2.5 mg idraparinux and equimolar dose of 3.0 mg idrabiotaparinux) may be an effective and safe alternative to conventional anticoagulation treatment for acute DVT.
Descrição
Palavras-chave
Pentasaccharides, Treatment, Deep vein thrombosis