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Adding Dipyridamole to Aspirin Improves Secondary Prevention After Stroke

The combination of aspirin plus dipyridamole might become the treatment of choice for routine secondary prevention.

In a large previously published study of patients with recent strokes or transient ischemic attacks (TIAs), dipyridamole plus aspirin reduced 2-year risk for all major vascular events by 22% compared with aspirin alone (J Neurol Sci 1996; 143:1); however, four smaller studies showed no such benefit, and the combination of dipyridamole plus aspirin seems to have no advantage over aspirin alone after other types of vascular events.

In this new multinational trial, researchers randomized more than 2700 patients (mean age, 63; 66% male) with TIAs or minor ischemic strokes within the previous 6 months to receive daily aspirin (30–325 mg) with or without dipyridamole (200 mg twice daily). No placebo was given, and the distribution of aspirin dosages was similar in both groups. Patients with a possible cardiac source of embolism were excluded.

During a mean 3.5-year follow-up, significantly fewer patients assigned to combination therapy than to aspirin alone reached the primary outcome of vascular death, nonfatal stroke, myocardial infarction, or major bleeding complications (13% vs. 16%). One third of dipyridamole patients discontinued their medication during the trial (most often because of headache), compared with 13% of aspirin-alone patients. A meta-analysis of results from this trial plus five others in which dipyridamole plus aspirin was compared with aspirin alone showed an 18% relative risk reduction for major vascular events with combination therapy.

Comment: Although it remains unclear why dipyridamole selectively benefits patients with cerebrovascular disease, the combination of aspirin plus dipyridamole might become the treatment of choice for routine secondary prevention after stroke. In another recent trial, researchers showed no added benefit when clopidogrel was added to aspirin, but that study included a broad range of at-risk patients — not simply patients with recent strokes or TIAs (Journal Watch Mar 21 2006). A multicenter trial in which clopidogrel is being compared directly with aspirin plus dipyridamole is in progress and is listed at clinicaltrials.gov.

— Bruce Soloway, MD

Published in Journal Watch General Medicine June 9, 2006

Citation(s):

The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): Randomised controlled trial. Lancet 2006 May 20; 367:1665-73.

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