title: The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis.
abstract: Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed and found to be at least noninferior to VKAs with regard to efficacy, but the risk of bleeding with TSOACs remains controversial. We performed a systematic review and meta-analysis of phase-3 randomized controlled trials (RCTs) to assess the bleeding side effects of TSOACs compared with VKAs in patients with venous thromboembolism or atrial fibrillation. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials; conference abstracts; and www.clinicaltrials.gov with no language restriction. Two reviewers independently performed study selection, data extraction, and study quality assessment. Twelve RCTs involving 102 607 patients were retrieved. TSOACs significantly reduced the risk of overall major bleeding (relative risk [RR] 0.72, P < .01), fatal bleeding (RR 0.53, P < .01), intracranial bleeding (RR 0.43, P < .01), clinically relevant nonmajor bleeding (RR 0.78, P < .01), and total bleeding (RR 0.76, P < .01). There was no significant difference in major gastrointestinal bleeding between TSOACs and VKAs (RR 0.94, P = .62). When compared with VKAs, TSOACs are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant nonmajor bleeding, and total bleeding. Additionally, TSOACs do not increase the risk of gastrointestinal bleeding.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Medicine, Chiang Mai University, Chiang Mai, Thailand; and.
authors.forename: Chatree
authors.initials: C
authors.lastname: Chai-Adisaksopha
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada;
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.affiliation: Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Isayama
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada;
authors.forename: Wendy
authors.initials: W
authors.lastname: Lim
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D014812:Vitamin K