Antiplatelet therapy in the prevention of stroke

Abstract

Aspirin (acetylsalicylic acid) is effective in reducing vascular outcome events in patients with atherosclerosis: a relative risk reduction of about 30% for stroke, 22% for stroke and death, and 15% for vascular mortality. It is probable that low and high dose aspirin are similar in efficacy. Complications are more frequent with high dose aspirin than with low doses. Four randomised trials evaluating sulfinpyrazone vs placebo, and 3 trials evaluating sulfinpyrazone vs aspirin, showed more cerebrovascular events in the sulfinpyrazone group than in the aspirin and placebo groups. One small trial comparing dipyridamole with placebo in patients with cerebrovascular disease found no difference between the 2 groups in outcome. No other studies have compared dipyridamole alone with placebo or aspirin. The European Stroke Prevention Study II is currently in progress and is comparing dipyridamole + aspirin, dipyridamole, aspirin, and placebo. In the first year, the Ticlopidine Aspirin Stroke Study (TASS) showed a 42% risk reduction for stroke and death using the efficacy analysis and a 47% risk reduction for stroke and stroke death. Ticlopidine was more effective than aspirin in reducing stroke in both males and females. Apart from a reversible severe neutropenia in 0.86% of patients, ticlopidine-related adverse effects were relatively benign and reversible. The Canadian-American Ticlopidine Study (CATS) compared ticlopidine with placebo in patients with completed major strokes. The cumulative event rates for the primary outcome events of stroke, myocardial infarction and vascular death, using the efficacy approach, show clear evidence of separation almost immediately after randomisation, consistent with a constant risk reduction of about 30% in the ticlopidine group. These data provide strong evidence that ticlopidine conveys a clinically important reduction in the risk of thromboembolic events in patients with a history of completed thromboembolic stroke. In conclusion, aspirin is effective in preventing atherothrombotic morbidity and mortality. It reduces the overall vascular event rate by about 25%. Sulfinpyrazone and dipyridamole appear to add nothing important over aspirin alone. Ticlopidine is more effective than aspirin in preventing stroke. The modest, reversible risk of neutropenia, affecting less than 1% of patients, makes the benefit: risk ratio a reasonable one.