Digestion of the Antiplatelets Comparison of PRoFESS

Abstract

Marc Fisher MD Kennedy Lees MD Section Editors Recently, the results of the Prevention Regimen for EFfectively avoiding Second Strokes trial (PRoFESS) were published after they had been presented at the European Stroke Conference in Nice, May 2008.1 It was a large multicenter clinical trial among over 20 000 patients with a recent (mainly <3 months) ischemic stroke that was of noncardioembolic origin in virtually all. The trial had 2 treatment contrasts that were studied simultaneously, one on 2 antiplatelet regimens, the other on telmisartan versus placebo.2 This comment addresses only the comparison of aspirin (25 mg) plus extended-release dipyridamole (200 mg) twice daily (ASA-ERDP) versus clopidogrel (75 mg) once daily. Primary outcome was recurrent stroke and secondary outcome the AntiPlatelet Trialists’ composite of vascular death, nonfatal myocardial infarction, or nonfatal stroke. Mean follow-up was 2.5 years. There were 916 recurrent strokes (primary outcome) with ASA-ERDP versus 898 with clopidogrel with a resulting hazard ratio (HR) of 1.01 (95% CI, 0.92 to 1.11). In both groups, there were 1333 vascular events (stroke, myocardial infarction, or vascular death); the HR was 0.99 (95% CI, 0.92 to 1.07) and the corresponding relative risk reduction (RRR) 1% (95% CI, −7% to 8%). In the ASA-ERDP group, there were more major hemorrhages (419) than in the clopidogrel group (365; HR, 1.15; 95% CI, 1.00 to 1.32). There was an excess of 44 intracranial hemorrhages with ASA-ERDP (147) as compared with clopidogrel (103; HR, 1.42; 95% CI, 1.11 to 1.83). For the tertiary outcome “stroke or major hemorrhage,” the HR was 1.03 (95% CI, 0.95 to 1.12). Patients on ASA-ERDP more often discontinued their study drug early (29.1%) than patients on clopidogrel (22.6%; 6.5% difference; 95% CI, 5.3% to 7.7%). Headache was the adverse event leading to permanent discontinuation of study drug in …