title: A meta-analysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists.
abstract: Apixaban is one of the new oral anticoagulants, which is prescribed as an alternative to vitamin K antagonists (VKAs). Concerns regarding its bleeding profile persist and require further evaluation. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to compare the risks of bleeding and all-cause mortality between apixaban and VKAs. The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials databases were systematically searched for RCTs comparing the risks of bleeding and all-cause mortality of apixaban (2.5 or 5 mg twice daily) with those of VKAs. We included RCTs conducted in adults and published in English or French. Data were pooled across RCTs using random-effects meta-analytical models. Our systematic search identified 5 RCTs meeting our inclusion criteria (n = 24,435). They included patients with atrial fibrillation (n = 18,358), total knee replacement surgery (n = 458), and venous thromboembolism (n = 5,619). Data pooled across RCTs revealed that apixaban was associated with reduced risks of any bleeding (relative risk [RR] 0.73, 95% confidence interval [CI] 0.59 to 0.90) and a composite of major or clinically relevant nonmajor bleeding (RR 0.60, 95% CI 0.40 to 0.88). Apixaban was also associated with a lower risk of intracranial bleeding (RR 0.42, 95% CI 0.31 to 0.58) whereas analyses of major and minor bleeding were inconclusive. Moreover, apixaban was associated with decreased all-cause mortality (RR 0.89, 95% CI 0.81 to 0.99) although this finding was driven by the results of the ARISTOTLE trial. In conclusion, our meta-analysis found that apixaban is associated with a lower risk of bleeding than VKAs, providing some reassurance regarding its safety.
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada; Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Lahoud
authors.initials: L
authors.lastname: Touma
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada; Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
authors.forename: Renée
authors.initials: R
authors.lastname: Atallah
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Eberg
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada; Faculty of Medicine, McGill University, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Quebec, Canada. Electronic address: mark.eisenberg@mcgill.ca.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Eisenberg
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D014943:Global Health; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use; D011728:Pyridones / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; D014812:Vitamin K; C522181:apixaban