(Circulation. 1999;100:1667-1672.)
© 1999 American Heart Association, Inc.
Cardiovascular Drugs |
Ticlopidine and Clopidogrel
From the Department of Clinical Pharmacology, The Royal College of Surgeons in Ireland, Dublin, Ireland.
Correspondence to Professor Desmond Fitzgerald, Department of Clinical Pharmacology, The Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. E-mail dfitzgerald{at}rcsi.ie
Abstract—The thienopyridines ticlopidine and clopidogrel are inhibitors of platelet function in vivo. Their mode of action has not been defined, but it appears that they require conversion to as yet unidentified metabolites that are noncompetitive antagonists of the platelet ADP receptor. Inhibition of platelet aggregation with these compounds is delayed until 24 to 48 hours after administration. Maximum inhibition occurs after 3 to 5 days, and recovery is slow after drug withdrawal. Ticlopidine is effective in preventing cardiovascular events in cerebrovascular, cardiovascular, and peripheral vascular disease, with an efficacy that is similar to aspirin. However, its use is associated with significant and sometimes fatal adverse reactions, specifically neutropenia and bone marrow aplasia. Gastrointestinal side effects and skin rashes are common and result in discontinuation of therapy in up to 10% of patients. Clopidogrel is at least as effective as aspirin in preventing cardiovascular events in patients with a history of vascular disease. It appears to be safer than ticlopidine, although its efficacy in acute coronary syndromes or post–coronary-stent insertion has not been reported. Important outstanding issues are whether clopidogrel adds to the benefit of aspirin and whether the combination of these agents is safe. If so, this combination may become the standard for antithrombotic therapy in cardiovascular disease.
Key Words: antiplatelets • clopidogrel • ticlopidine
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