Risk of Gastrointestinal Bleeding in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. However, these drugs have been associated with an increased risk of gastrointestinal (GI) bleeding. We conducted a systematic review and meta-analysis to determine the risk of GI bleeding in patients receiving these drugs.

METHODS: We searched the EMBASE, Medline, Cochrane, and ISI Web of knowledge databases through January 2016 for randomized trials that compared NOACs with conventional anticoagulants for approved indications. We conducted a meta-analysis, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was major GI bleeding. Secondary outcomes included clinically relevant nonmajor bleeding and upper and lower GI bleeding. We performed a priori subgroup analyses by individual drug.

RESULTS: Our analysis included a total of 43 randomized trials, comprising 166,289 patients. There was no difference between NOACs and conventional anticoagulants in the risk of major bleeding (1.5% vs 1.3%, respectively; OR, 0.98; 95% CI, 0.80-1.21), clinically relevant nonmajor bleeding (0.6% vs 0.6%, respectively; OR, 0.93; 95% CI, 0.64-1.36), upper GI bleeding (1.5% vs 1.6%, respectively; OR, 0.96; 95% CI, 0.77-1.20), or lower GI bleeding (1.0% vs 1.0%, respectively; OR, 0.88; 95% CI, 0.67-1.15). Dabigatran (2.0% vs 1.4%, respectively; OR, 1.27; 95% CI, 1.04-1.55) and rivaroxaban (1.7% vs 1.3%, respectively; OR, 1.40; 95% CI, 1.15-1.70) were associated with increased odds of major GI bleeding compared with conventional anticoagulation, whereas no difference was found for apixaban (0.6% vs 0.7%, respectively; OR, 0.81; 95% CI, 0.64-1.02) or edoxaban (1.9% vs 1.6%, respectively; OR, 0.93; 95% CI, 0.78-1.11). These subgroup findings were not observed in other sensitivity analyses.

CONCLUSIONS: In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs.