Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation

Background: We aimed to identify different stroke prevention treatments for atrial fibrillation assessed in randomized controlled trials and to compare them within a single evidence synthesis framework. Methods: We updated the Cochrane review on anticoagulants and antiplatelet therapy for nonrheumatic atrial fibrillation to include randomized controlled trials published between January 2000 and March 2005 identified via the CENTRAL database and MEDLINE. A mixed-treatment comparison method was used to combine direct within-trial, between-treatment comparisons with indirect trial evidence while maintaining randomization. Results: Data were combined from 19 clinical trials that included 17 833 patients randomized to 9 treatment strategies, including placebo. For prevention of ischemic stroke, adjusted standard-dose warfarin sodium (relative rate [RR], 0.35; 95% credible interval [CrI], 0.24 to 0.52), adjusted low-dose warfarin (RR, 0.35; 95% CrI, 0.19 to 0.60), ximelagatran (RR, 0.34; 95% CrI, 0.18 to 0.61), and aspirin (RR, 0.64; 95% CrI, 0.44 to 0.88) were all associated with a significantly lower rate of ischemic stroke compared with placebo. For major and fatal bleeding episodes, there was some evidence of an increased risk for all treatments but none were statistically significant. Assuming a baseline risk of 51 ischemic stroke events per 1000 person-years, it can be estimated that adjusted standard-dose warfarin could prevent 28 (95% CrI, -37 to -19) ischemic strokes at the expense of 11 (95% CrI, -1 to +/- 39) major or fatal bleeding episodes. In comparison, aspirin could prevent 16 (95% CrI, -26 to -5) ischemic strokes at the expense of 6 (95% CrI, -3 to +27) major or fatal bleeding episodes. Conclusions: A lower rate of ischemic stroke and a higher rate of major bleeding episodes were found to be associated with oral anticoagulants compared with aspirin, and both anticoagulants and aspirin were found to be associated with a reduction in the rate of stroke compared with placebo.