Ticlopidine and clopidogrel

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 n oncompetitive antagonists of the platelet ADP receptor. Inhibition of plate let aggregation with these compounds is delayed until 24 to 48 hours after administration. Maximum inhibition occurs after 3 to 5 days, and recovery i s slow after drug withdrawal. Ticlopidine is effective in preventing cardio vascular 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, specific ally neutropenia and bone marrow aplasia, Gastrointestinal side effects and skin rashes are common and result in discontinuation of therapy in up to 1 0% of patients. Clopidogrel is at least as effective as aspirin in preventi ng cardiovascular events in patients with a history of vascular disease. It appears to be safer than ticlopidine, although its efficacy in acute coron ary syndromes or post-coronary-stent insertion has not been reported. Impor tant outstanding issues are whether clopidogrel adds to the benefit of aspi rin and whether the combination of these agents is safe. If so, this combin ation may become the standard for antithrombotic therapy in cardiovascular disease.