Adjusted indirect meta-analysis of aspirin plus warfarin at international normalized ratios 2 to 3 versus aspirin plus clopidogrel after acute coronary syndromes.

After acute coronary syndromes, the beneficial effect of aspirin plus clopidogrel (A+C) or aspirin plus dose-adjusted warfarin (A+W) compared with aspirin alone is well established. However, these regimens were never compared. To compare the risk-benefit profile of A+C versus A+W after acute coronary syndromes, major medical databases for randomized controlled trials comparing 1 of these combined approaches versus aspirin alone after an acute coronary syndrome (updated June 2006) were searched. Evaluated end points were major adverse events [MAEs: all-cause death, acute myocardial infarction [AMI], thromboembolic stroke, major bleeds, and overall risk of stroke [hemorrhagic or ischemic]). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for (1) A+W versus aspirin alone, (2) A+C versus aspirin alone, and (3) A+W versus A+C using adjusted indirect meta-analysis. Thirteen studies were included, totaling 69,741 patients. Ten compared A+W versus aspirin alone and 3 compared A+C versus aspirin alone. Each combined approach yielded a significantly lower risk of MAEs, albeit an increased risk of major bleeds, compared with aspirin alone. No significant difference was found for A+W versus A+C for risk of overall MAEs, death, or AMI. However, A+W versus A+C was associated with a significantly lower risk of thromboembolic stroke (OR 0.53, 95% CI 0.31 to 0.88, number needed to treat 60) and all types of stroke (OR 0.58, 95% CI 0.35 to 0.94, p=0.038), but also with increased risk of major bleeds (OR 1.9, 95% CI 1.2 to 2.8, number needed to harm 300). In conclusion, after an acute coronary syndrome, A+W and A+C are comparable in the prevention of MAEs, death, and AMI compared with aspirin alone. Allocating 100 patients to A+W (at international normalized ratio 2 to 3) with respect to A+C could prevent 17 thromboembolic strokes while causing 3 major bleeds.