Lana A Castellucci1, Chris Cameron2, Grégoire Le Gal1, Marc A Rodger1, Doug Coyle2, Philip S Wells1, Tammy Clifford3, Esteban Gandara1, George Wells4, Marc Carrier1. 1. Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. 2. Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. 3. Canadian Agency for Drugs and Technologies in Health, Ottawa, Ontario, Canada. 4. Ottawa Heart Institute, Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Abstract
IMPORTANCE: Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe. OBJECTIVE: To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism. DATA SOURCES: A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014. STUDY SELECTION: Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively. RESULTS: Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination. CONCLUSIONS AND RELEVANCE: Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.
IMPORTANCE: Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe. OBJECTIVE: To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism. DATA SOURCES: A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014. STUDY SELECTION: Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively. RESULTS: Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination. CONCLUSIONS AND RELEVANCE: Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.
Authors: Danielle Menosi Gualandro; Pai Ching Yu; Bruno Caramelli; André Coelho Marques; Daniela Calderaro; Luciana Savoy Fornari; Claudio Pinho; Alina Coutinho Rodrigues Feitosa; Carisi Anne Polanczyk; Carlos Eduardo Rochitte; Carlos Jardim; Carolina L Z Vieira; Debora Y M Nakamura; Denise Iezzi; Dirk Schreen; Eduardo Leal Adam; Elbio Antonio D'Amico; Emerson Q de Lima; Emmanuel de Almeida Burdmann; Enrique Indalecio Pachón Mateo; Fabiana Goulart Marcondes Braga; Fabio S Machado; Flavio J de Paula; Gabriel Assis Lopes do Carmo; Gilson Soares Feitosa-Filho; Gustavo Faibischew Prado; Heno Ferreira Lopes; João R C Fernandes; José J G de Lima; Luciana Sacilotto; Luciano Ferreira Drager; Luciano Janussi Vacanti; Luis Eduardo Paim Rohde; Luis F L Prada; Luis Henrique Wolff Gowdak; Marcelo Luiz Campos Vieira; Maristela Camargo Monachini; Milena Frota Macatrão-Costa; Milena Ribeiro Paixão; Mucio Tavares de Oliveira; Patricia Cury; Paula R Villaça; Pedro Silvio Farsky; Rinaldo F Siciliano; Roberto Henrique Heinisch; Rogerio Souza; Sandra F M Gualandro; Tarso Augusto Duenhas Accorsi; Wilson Mathias Journal: Arq Bras Cardiol Date: 2017 Jan-Feb Impact factor: 2.000
Authors: André Arpad Faludi; Maria Cristina de Oliveira Izar; José Francisco Kerr Saraiva; Ana Paula Marte Chacra; Henrique Tria Bianco; Abrahão Afiune; Adriana Bertolami; Alexandre C Pereira; Ana Maria Lottenberg; Andrei C Sposito; Antonio Carlos Palandri Chagas; Antonio Casella; Antônio Felipe Simão; Aristóteles Comte de Alencar; Bruno Caramelli; Carlos Costa Magalhães; Carlos Eduardo Negrão; Carlos Eduardo Dos Santos Ferreira; Carlos Scherr; Claudine Maria Alves Feio; Cristiane Kovacs; Daniel Branco de Araújo; Daniel Magnoni; Daniela Calderaro; Danielle Menosi Gualandro; Edgard Pessoa de Mello; Elizabeth Regina Giunco Alexandre; Emília Inoue Sato; Emilio Hideyuki Moriguchi; Fabiana Hanna Rached; Fábio César Dos Santos; Fernando Henpin Yue Cesena; Francisco Antonio Helfenstein Fonseca; Henrique Andrade Rodrigues da Fonseca; Hermes Toros Xavier; Isabela Cardoso Pimentel Mota; Isabela de Carlos Back Giuliano; Jaqueline Scholz Issa; Jayme Diament; João Bosco Pesquero; José Ernesto Dos Santos; José Rocha Faria; José Xavier de Melo; Juliana Tieko Kato; Kerginaldo Paulo Torres; Marcelo Chiara Bertolami; Marcelo Heitor Vieira Assad; Márcio Hiroshi Miname; Marileia Scartezini; Neusa Assumpta Forti; Otávio Rizzi Coelho; Raul Cavalcante Maranhão; Raul Dias Dos Santos; Renato Jorge Alves; Roberta Lara Cassani; Roberto Tadeu Barcellos Betti; Tales de Carvalho; Tânia Leme da Rocha Martinez; Viviane Zorzanelli Rocha Giraldez; Wilson Salgado Journal: Arq Bras Cardiol Date: 2017-07 Impact factor: 2.000