Bleeding risk in randomized controlled trials comparing warfarin and aspirin: a systematic review and meta‐analysis

BACKGROUND: Warfarin and aspirin (acetylsalicylic acid [ASA]) are the most commonly used anticoagulant and antiplatelet drugs in the treatment of cardiovascular disease. OBJECTIVES: To provide a pooled estimate of the bleeding risk from randomized controlled trials (RCTs) comparing warfarin and ASA at the dose ranges recommended in evidence-based guidelines. PATIENTS/METHODS: Ovid MEDLINE, Embase and the Cochrane Library, up to September 2011, were searched for RCTs comparing bleeding rates in adult patients randomized to warfarin, target International Normalized Ratio (INR) 2.0-3.5, and ASA, 50-650 mg daily, with at least 3 months of follow-up. Pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated with the inverse variance method and the random effects model. RESULTS: Four thousand four hundred and forty-two abstracts were screened, resulting in eight included studies for final analysis. A pooled estimate derived from the 2904 patients enrolled indicated a trend towards an increase in major bleeding risk in those randomized to warfarin (OR 1.27; 95% CI 0.83-1.94). The pooled OR for intracranial hemorrhage in patients treated with warfarin vs. ASA was 1.64 (95% CI 0.71-3.78), and that for extracranial major bleeding was 1.03 (95% CI 0.61-1.75). Minor bleeding, from a 1748-patient sample, was more common in warfarin patients (OR 1.50; 95% CI 1.13-2.00). CONCLUSIONS: This meta-analysis failed to find a statistically significant difference in major bleeding between warfarin, target INR 2.0-3.5, and ASA, 50-650 mg daily. The trend towards increased bleeding with warfarin appears to be explained by an excess of intracranial bleeding in warfarin patients.