(Stroke. 2000;31:1779.)
© 2000 American Heart Association, Inc.
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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
From the Department of Medicine (G.J.H.), University of Western Australia, Perth, Australia; Clinical Trial Service Unit (C.L.M.S.), University of Oxford, Oxford, UK; and the University of Tasmania (D.W.D.), Tasmania, Australia.
Correspondence to Dr Cathie Sudlow, Specialist Registrar in Neurology, Department of Neurology, Derriford Hospital, Plymouth PL6 8DH, UK. E-mail cathie.sudlow{at}platelet.freeserve.co.uk
Background and Purpose—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.
Methods—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.
Results—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 
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 2-fold and clopidogrel by approximately one third).
Only ticlopidine increased the odds of neutropenia.
Conclusions—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.
Key Words: cardiovascular diseases • cerebrovascular disorders • meta-analysis • platelet aggregation • randomized controlled trials
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