Clinical considerations in selecting antiplatelet therapy in cerebrovascular disease

Abstract

Effective antiplatelet drugs--aspirin, ticlopidine, dipyridamole, and clopidogrel--are reviewed. Aspirin has remained the pharmacologic foundation of stroke prevention, primarily because of its low cost. It has been shown to provide a 22% relative risk reduction of stroke in high-risk patients. Its principal adverse effect is gastrotoxicity. Ticlopidine has been widely used in patients with a high risk of stroke who are sensitive to aspirin or in whom aspirin has failed. It has been associated with a median reduction in adenosine diphosphate-induced platelet aggregation of 70% in about 8-11 days. Ticlopidine has been shown to be superior to aspirin at three years in preventing stroke. The principal adverse effects are diarrhea and rash; there has been a 2.4% occurrence of neutropenia. In a trial comparing aspirin, dipyridamole, and a combination of the two, the risk of stroke was 18% lower with aspirin, 16% lower with dipyridamole, and 37% lower with combination therapy compared with placebo. The adverse-effect profile of dipyridamole has proven to be less problematic than that of aspirin or ticlopidine. In a trial comparing clopidogrel with aspirin, patients receiving clopidogrel had an annual 5.32% risk of ischemic stroke, myocardial infarction, or vascular death compared with 5.83% for patients receiving aspirin. Clopidogrel has been associated with a small occurrence of rash and diarrhea, and gastrointestinal intolerance and hemorrhage were less frequent with clopidogrel than with aspirin. Both aspirin and clopidogrel are associated with a low occurrence of neutropenia. Aspirin, ticlopidine, dipyridamole, and clopidogrel have earned a role in stroke prevention; the different adverse-effect profiles of the drugs will influence the choice of agent.