Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis.

BACKGROUND AND PURPOSE Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of combined aspirin-dipyridamole or clopidogrel are not known in patients with acute ischemic stroke. METHODS The factorial PRoFESS secondary prevention trial assessed antiplatelet and blood pressure-lowering strategies in 20,332 patients, 1360 of whom were randomized within 72 hours of ischemic stroke to combined aspirin (Asp; 25 mg BID) and extended-release dipyridamole (ER-DP; 200 mg BID, n=672) or clopidogrel (75 mg/d, n=688). The primary outcome for this post hoc subgroup analysis was functional outcome at 30 days; secondary outcomes included recurrence and death by 90 days. Analyses were adjusted for baseline prognostic variables and blood pressure treatment assignment. RESULTS Patients were representative of the whole trial (age 67 years, National Institutes of Health Stroke Scale score 3, small-artery occlusion 59%), and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. By 90 days, treatment was no longer being taken in 121 (18%) patients randomized to Asp/ER-DP and in 86 (12.5%) assigned to clopidogrel (P=0.006). Combined death or dependency (shift analysis of modified Rankin Scale score at day 30) did not differ between treatment groups (odds ratio [OR]=0.97; 95% CI, 0.79 to 1.19). Nonsignificant trends to reduced recurrence (OR=0.56; 95% CI, 0.26 to 1.18) and vascular events (OR=0.71; 95% CI, 0.36 to 1.37) were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups. CONCLUSIONS Treatment with combined Asp/ER-DP vs clopidogrel in 1360 patients with acute, mild ischemic stroke did not differ in terms of effects on functional outcome, recurrence, death, bleeding, or serious adverse events. Both treatments were practical to administer.