Thienopyridines or Aspirin to Prevent Stroke and Other Serious Vascular Events in Patients at High Risk of Vascular Disease?

Abstract

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; 2Pϭ0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for Ϸ2 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 Ϸ2-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.

Selective Inhibition of Cyp2b6-Catalyzed Bupropion Hydroxylation in Human Liver Microsomes in Vitro

“…The risk of drug interactions or central nervous system toxicity associated with bupropion may be of clinical importance and correlates with high bupropion or metabolite levels. Since ticlopidine has been approved as an antiplatelet drug for patients at high risk of vascular disease, its use is expected to increase (Hankey et al, 2000). Ticlopidine is a thienopyridine chemically related to the other member of the group, clopidogrel (Algra and van Gijn, 2000).…”

Conventional and Novel Pharmacotherapy of Angina Pectoris

“…Ticlopidine is another thienopyridine that has been shown to have effects on treatment of unstable angina. But according to the results of some studies, ticlopidine have more adverse effects than clopidogrel (Hankey, Sudlow et al 2000). Aspirin has clot-preventing properties within the coronary arteries or other blood vessels.…”

Review of Prasugrel for the Secondary Prevention of Atherothrombosis

“…6 Ticlopidine was used in the past for prevention of subacute stent thrombosis, 13 but the adverse effects of the drug (principally rash and diarrhea, but also the potential for neutropenia [reported in approximately 2.4% of patients]) limit its utility. 14,15 Therefore, clopidogrel, which lacks the adverse effect of neutropenia, 15 has become the most offer additive effects when given with aspirin because of their differing but complementary mechanism of action. Like clopidogrel, prasugrel is a thienopyridyl prodrug.…”