title: Meta-analysis of rivaroxaban and bleeding risk.
abstract: Rivaroxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unclear. Reported randomized controlled trials comparing the safety of rivaroxaban with that of vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon, and fluindione) were systematically searched. Inclusion was restricted to studies of ≥30 days' treatment duration. Safety end points examined included major and clinically relevant nonmajor bleeding, as well as mortality. Data were pooled across randomized controlled trials using random-effects meta-analysis models. Five randomized controlled trials including 23,063 patients that met the inclusion criteria were identified. Patients received treatment for nonvalvular atrial fibrillation (n = 14,264), deep vein thrombosis (n = 3,967), or acute symptomatic pulmonary embolism (n = 4,832). Overall, rivaroxaban was not associated with the risk of a composite end point of major or clinically relevant nonmajor bleeding (relative risk 0.99, 95% confidence interval 0.93 to 1.06). However, rivaroxaban was associated with a significant decrease in fatal bleeding (relative risk 0.48, 95% confidence interval 0.31 to 0.74). In 2 studies reporting intracranial bleeding events, rivaroxaban was associated with decreased risk compared with vitamin K antagonists. It was not associated with decreased risk for all-cause mortality (relative risk 0.89, 95% confidence interval 0.73 to 1.09). In conclusion, with a decrease in fatal bleeding and no suggestion of an increase in all-cause mortality, rivaroxaban has a favorable safety profile with respect to bleeding.
authors: Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
authors: Guila
authors: G
authors: Wasserlauf
authors: Sonia M
authors: SM
authors: Grandi
authors: Kristian B
authors: KB
authors: Filion
authors: Mark J
authors: MJ
authors: Eisenberg
mesh_terms: D002423:Cause of Death; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality; D006801:Humans; D009025:Morpholines / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D000069552:Rivaroxaban; D013876:Thiophenes / Q000009:adverse effects* / Q000627:therapeutic use; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D000069552:Rivaroxaban