Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials.

Abstract

Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately 2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by approximately 2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.