Comparison of the Efficacy and Safety of Non-vitamin K Antagonist Oral Anticoagulants with Warfarin in Atrial Fibrillation Patients with a History of Bleeding: A Systematic Review and Meta-Analysis.

Abstract

Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF and a history of bleeding were excluded from pivotal trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. We therefore aimed to assess the efficacy and safety of NOACs compared with warfarin in patients with AF and a history of bleeding. We conducted a systematic review of retrospective studies and clinical trials using the PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases to May 2021. Overall, 56,697 patients from six studies were included. NOACs significantly reduced the risk of ischemic stroke (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91; p=0.005), fatal ischemic stroke (HR 0.49, 95% CI 0.39-0.61; p<0.001), all-cause mortality (HR 0.70, 95% CI 0.50-0.98; p=0.04), major bleeding events (HR 0.75, 95% CI 0.67-0.84; p<0.001), intracranial hemorrhage (ICH; HR 0.63, 95% CI 0.48-0.82; p<0.001), fatal ICH (HR 0.33, 95% CI 0.20-0.56, p<0.001), and gastrointestinal bleeding (HR 0.83, 95% CI 0.72-0.96; p=0.01). NOACs showed better efficacy and safety profile compared with warfarin in patients with AF and a history of bleeding. Randomized controlled trials are warranted to validate these findings.