Commonly prescribed treatment options to prevent recurrent stroke include aspirin, clopidogrel, and an aspirin/dipyridamole combination. In the double-blind randomized PRoFESS trial, 20,332 clinically stable patients (age,
50) with recent ischemic strokes received either the fixed combination of aspirin (25 mg) plus extended-release dipyridamole (200 mg) given twice daily, or clopidogrel (75 mg) given once daily. The study was sponsored by the maker of the aspirin/dipyridamole combination (Aggrenox).During a mean follow-up of 2.5 years, recurrent stroke occurred in 9.0% of aspirin/dipyridamole recipients and in 8.8% of clopidogrel recipients — a nonsignificant difference. The incidence of a secondary composite outcome (stroke, myocardial infarction, or death from vascular causes) was 13.1% in both groups. A slight excess incidence of major hemorrhage with aspirin/dipyridamole compared with clopidogrel (4.1% vs. 3.6%) was of borderline significance, but a composite endpoint of stroke or major hemorrhage was similar in the two groups. Aspirin/dipyridamole recipients were significantly more likely than aspirin recipients to discontinue study medication, mainly because of headaches.
Comment: Aspirin/dipyridamole and clopidogrel appear to be similarly efficacious in preventing recurrent stroke. Headaches are more common with aspirin/dipyridamole but usually diminish with time. Editorialists discuss the dilemma of interpreting the PRoFESS trial in the context of previous studies. Two previous large trials showed aspirin/dipyridamole to be superior to aspirin alone (JW Jun 9 2006); in contrast, the one previous large trial in which clopidogrel was compared with aspirin monotherapy did not show a convincing advantage for clopidogrel in stroke patients (JW Dec 10 1996). Based on previous results, aspirin/dipyridamole should have been superior to clopidogrel in PRoFESS, but was not. Using a technique called "network meta-analysis" (in which dissimilar trials are analyzed together), the editorialists conclude that aspirin/dipyridamole and clopidogrel are equally efficacious and that both are somewhat, but not quite significantly, better than aspirin alone. Thus, cost and side-effect profiles should probably factor into physicians’ choices among these treatments.
— Allan S. Brett, MD
Published in Journal Watch General Medicine September 4, 2008
Citation(s):
Sacco RL et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008 Aug 27; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa0805002)