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Low-dose and high-dose acetylsalicyclic acid, with and without dipyridamole

A review of clinical trial results

From the Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, The Netherlands.

Address correspondence and reprint requests to Dr. Jan G.P. Tijssen, University of Amsterdam, Academic Medical Center, Room J2-221, Bx 22700, Meibergdreef 9, Amsterdam, 1100 DE, The Netherlands.

Abstract.

Publication of the results of the second European Stroke Prevention Study(ESPS-2) provided the incentive for an update of the meta-analyses of aspirin and dipyridamole in the secondary prevention of stroke. After review of published randomized trials of prolonged treatment with aspirin, dipyridamole, or their combination in patients with a history of stroke or transient ischemic attack (TIA), data on the occurrence of stroke, myocardial infarction, and vascular death were used to calculate overall relative risk reductions. The relative risk reduction for aspirin versus placebo was 13%. The same relative risk reduction was found in separate meta-analyses of trials with high (1,000-1,500 mg), medium (250-500 mg), and low (50-100 mg) doses of aspirin. Trials in which different doses were compared showed no difference in the occurrence of vascular events. The addition of dipyridamole to low-dose aspirin further reduced the risk for vascular events by 15%. We conclude from current trials that low-dose aspirin alone reduced the risk of vascular events in patients with prior stroke or TIA by 13%. There is no evidence of a dose-effect relationship. An additional reduction of the risk by 15% can be obtained by adding dipyridamole to aspirin. The overall evidence for the relative effects of the combination of dipyridamole and aspirin versus aspirin alone or placebo is highly consistent. The clinical evidence now favors the two agents in combination over aspirin alone.