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Aspirin plus Dipyridamole for Secondary Stroke Prevention?

The ESPRIT trial resolves a long-standing question.

Aspirin, the gold standard for secondary prevention of stroke of vascular origin, prevents less than one quarter of new vascular events. Two recent trials of dual therapy with aspirin plus clopidogrel did not show a benefit in secondary prevention of stroke (Journal Watch Cardiology Apr 20 2006 and Oct 8 2004). What about aspirin plus dipyridamole?

In the non–industry-funded ESPRIT trial, researchers randomized 2739 patients with a transient ischemic attack or minor ischemic stroke (of presumed arterial origin) in the previous 6 months to receive aspirin (30–325 mg daily) or aspirin plus dipyridamole (200 mg twice daily; 83% slow-release formulation). The median aspirin dose was 75 mg. Although auditing of outcomes was blinded, treatment was not. Routine MRI was not available to differentiate lacunar from cortical strokes.

During a mean follow-up of 3.5 years, incidence of the primary composite endpoint (vascular death, nonfatal stroke, nonfatal MI, or major bleeding) was significantly lower with combined therapy than with aspirin alone (13% vs. 16%; hazard ratio, 0.80). Significantly more combination-therapy than aspirin-alone recipients discontinued study medication (34% vs. 13%), largely because of headache. Adding the ESPRIT data to a previously published meta-analysis of randomized trials comparing aspirin plus dipyridamole with aspirin alone showed a significant overall benefit of dual therapy (risk ratio for preventing vascular death, stroke, or MI: 0.82; 95% CI, 0.74–0.91).

Comment: For secondary stroke prevention, dipyridamole plus aspirin was more effective than aspirin alone (and is likely to be cost-effective). Given this trial’s simple, pragmatic design with few exclusion criteria, the results are applicable to a broad range of patients with ischemic cerebral events of arterial origin. A strategy of dipyridamole titration to prevent drug-induced headache merits investigation. An editorialist endorses dual antiplatelet therapy for secondary stroke prevention but reminds us that risk-factor and lifestyle modification also matter.

— Beat J. Meyer, MD

Published in Journal Watch Cardiology June 22, 2006

Citation(s):

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

• Medline abstract (Free)

Norrving B. Dipyridamole with aspirin for secondary stroke prevention. Lancet 2006 May 20; 367:1638-9.

• Medline abstract (Free)