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Prevention of Recurrent Ischemic Stroke

Cost and side effects, not effectiveness, might be the discriminators between aspirin plus dipyridamole and clopidogrel.

Aspirin, aspirin plus dipyridamole, or clopidogrel often is used to prevent recurrent stroke. In the double-blind randomized PRoFESS trial, more than 20,000 clinically stable patients (age, 50) with recent ischemic strokes received either a fixed combination of aspirin (25 mg) plus extended-release dipyridamole (200 mg) twice daily or clopidogrel (75 mg) 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 combination 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 that occurred with aspirin plus dipyridamole compared with clopidogrel (4.1% vs. 3.6%) was of borderline significance, but incidence of a composite endpoint of stroke or major hemorrhage was similar in the two groups. Combination recipients were significantly more likely than clopidogrel recipients to discontinue study medication (JW Sep 4 2008).

Previously, the combination of aspirin plus dipyridamole was shown to be superior to aspirin alone, whereas clopidogrel had shown only a marginal benefit over aspirin alone. The PRoFESS trial (the first head-to-head comparison of the 2 regimens) was designed to establish superiority of aspirin plus dipyridamole over clopidogrel for prevention of recurrent stroke, but it failed to do so. Overall, the two regimens appear to be equally efficacious. However, this study complicates the issue of whether either of these regimens is substantially superior to aspirin alone. Using a technique called "network meta-analysis" (in which dissimilar trials are analyzed together), editorialists concluded that aspirin plus dipyridamole might be minimally superior to clopidogrel alone (although not significantly so), whereas clopidogrel might be minimally superior to aspirin alone (again, not significantly). As such, cost and side-effect profiles probably should factor into physicians’ choices among these treatments for individual patients.

— Jamaluddin Moloo, MD, MPH

Published in Journal Watch General Medicine December 29, 2008

Reader Remarks:

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• Clopidogrel still better
  Dr RS Kumar Bhamidimarri, 2 Jun 2009 9:13 PM EST
  In patients with known disease in an another major vascular bed, clopidogrel is a better drug.