Aspirin and Extended-Release Dipyridamole vs. Clopidogrel for Recurrent Stroke

Abstract

Conclusion: Rates of recurrent stroke are similar in patients with stroke treated with aspirin and extended release dipyridamole vs those treated with clopidogrel. Summary: Surviving patients with ischemic stroke are at risk for recurrent stroke. Multiple trials have proven the efficacy of antiplatelet agents in prevention of recurrent stroke after non-cardioembolic stroke. Which particular antiplatelet therapy may work best in the prevention of recurrent stroke is unknown. This trial studied the relative efficacy and safety of aspirin plus extended-release dipyridamole (ERDP) for prevention of recurrent stroke compared with patients treated with clopidogrel. This is a double-blind, two-by-two factorial trial. Patients were randomly assigned to receive 75 mg of aspirin plus 200 mg of ERDP twice daily, or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary end point was a composite of myocardial infarction, stroke, or death from cardiovascular cause. The trial was designed as a noninferiority trial with sequential statistic testing of noninferiority, followed by superiority testing. A total of 20,332 patients were followed up worldwide, with a mean follow-up of 2.5 years. In patients receiving aspirin and ERDP, recurrent stroke occurred in 916 (9%). In patients receiving clopidogrel, recurrent stroke occurred in 898 (8.8%), with a hazard ratio (HR) of 1.01 (95% confidence interval [CI], 0.92-1.11). The secondary composite outcome occurred in 13.1% of patients in each group (HR for aspirin/ERDP, 0.99; 95% CI, 0.92-1.07). Patients treated with aspirin/ERDP had 4.1% (n = 419) major hemorrhagic events compared with 3.6% (n = 365) in patients treated with clopidogrel (HR, 1.15; 95% CI, 1.00-1.32) and had more intracranial hemorrhage (HR, 1.42; 95% CI, 1.11-1.83). The net risk of a major hemorrhagic event or recurrent stroke was similar in the two groups, 11.7% in the aspirin/ERDP group vs 11.4% in the clopidogrel group (HR, 1.03; 95% CI, 1.95-1.11). Comments: The study indicates no significant difference between the use of aspirin/ERDP vs clopidogrel in preventing recurrent stroke. This was a huge study with high patient numbers and international representation from 35 countries or regions. The results of the study, therefore, should be generalizable worldwide. Although the study failed to identify a superior treatment to prevent recurrent stroke, we now know the expected risk of recurrent stroke in patients treated according to the study protocol. The study has also provided us safety and efficacy data for physicians concerning individual treatment decisions for their patients with ischemic stroke.