Low Doses of Acetylsalicylic Acid Increase Risk of Gastrointestinal Bleeding in a Meta-Analysis

BACKGROUND & AIMS: We performed a meta-analysis of data from randomized trials to estimate the risk of allcause mortality and bleeding (and especially gastrointestinal [GI] bleeding) in patients treated with low doses of acetylsalicylic acid (ASA) (75-325 mg/d), alone or in combination with other medications. METHODS: We searched 10 electronic databases (until October 2010) and collected data on adverse events in randomized controlled studies that evaluated low doses of ASA, alone (35 trials) or in combination with anticoagulants (18 trials), clopidogrel (5 trials), or proton pump inhibitors (PPIs; 3 trials). We analyzed data using random-effects meta-analysis and meta-regression, applying Peto's odds ratio (OR) for adverse events. RESULTS: Low doses of ASA alone decreased the risk for all-cause mortality (relative risk, 0.93, 95% confidence interval [CI], 0.87-0.99), largely because of effects in secondary prevention populations. The risk of major GI bleeding increased with low doses of ASA alone (OR, 1.55; 95% CI, 1.27-1.90), compared with inert control reagents. The risk increased when ASA was combined with clopidogrel, compared with aspirin alone (OR, 1.86; 95% CI, 1.49-2.31), anticoagulants vs low doses of ASA alone (OR, 1.93; 95% CI, 1.42-2.61), or in studies that included patients with a history of GI bleeding or of longer duration. Importantly, PPI use reduced the risk for major GI bleeding in patients given low doses of ASA (OR, 0.34; 95% CI, 0.21-0.57). CONCLUSIONS: In a meta-analysis, low doses of ASA increased the risk for GI bleeding; risk increased with accompanying use of clopidogrel and anticoagulant therapies, but decreased in patients who took PPIs.