Comparison of antiplatelet regimens in secondary stroke prevention: a nationwide cohort study

Background: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent stroke associated with these three treatments. Methods: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding were calculated for each antiplatelet regimen. Results: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus the combination of acetylsalicylic acid and dipyridamole were 1.02 (95 % confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95 % CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95 % CI: 1.31-1.67) for stroke and 1.47 (95 % CI: 1.18-1.82) for bleeding. Clopidogrel versus acetylsalicylic acid yielded HRs of 0.69 (95 % CI: 0.59-0.81) and 0.72 (95 % CI: 0.55-0.96) for stroke and bleeding, respectively. The 1-year predicted risks associated with acetylsalicylic acid, the combination of acetylsalicylic acid and dipyridamole, and clopidogrel were 11.1 (95 % CI: 10.2-12.2), 7.7 (95 % CI: 7.3-8.3), and 8.0 (95 % CI: 6.9-8.7) for ischemic stroke, respectively; while, the risks for bleeding were 3.4 (95 % CI: 2.8-3.9), 2.4 (95 % CI: 2.1-2.7), and 2.4 (95 % CI: 1.9-2.9), respectively. Conclusion: Clopidogrel and the combination of acetylsalicylic acid and dipyridamole were associated with similar risks for recurrent ischemic stroke and bleeding; whereas acetylsalicylic acid was associated with higher risks for both ischemic stroke and bleeding. The latter finding may partially be explained by selection bias.