[Current pharmacological principles to inhibit platelet function and their clinical implications. Focus on...

Clopidogrel is a further-developed analog of ticlopidine and currently the only therapeutic alternative for long-term prophylaxis and therapy of atherothrombosis. According to the CAPRIE trial, clopidogrel causes significantly less gastrointestinal bleeding than plain aspirin (ASA). There is an increased antiplatelet efficacy by combining clopidogrel with ASA as shown in several clinical trials, such as CURE and CREDO. An active metabolite of clopidogrel causes irreversible inhibition of the P2Y12-ADP receptor at the platelet surface, but does not alter the metabolism of arachidonic acid. Clopidogrel has additional effects on the ADP-induced expression of adhesion molecules (P-selectin, GPIIb/IIIa) and inflammatory mediators (CD40L). These actions, shown ex vivo, might be clinically relevant. Similar to ASA there can be variable antiplatelet activities of Clopidogrel. Their frequency can not be precisely estimated yet. There is neither a generally accepted definition of insufficient responsiveness (against inhibitors of platelet function) nor any generally accepted procedure to measure it, including definition of normal range.