chapter  11
8 Pages

Emerging oral antiplatelet receptor inhibitors

WithLori-Ann Linkins, John W Eikelboom, Alexander G Turpie

Introduction Aspirin remains the cornerstone of antiplatelet therapy for the prevention and treatment of coronary, cerebral, and peripheral artery disease. 1 It has several attractive properties that have contributed to its success, including (i) once-daily oral administration, (ii) the ability to permanently inactivate a platelet protein (cyclooxygenase-1) that cannot be resynthesized during the life of the platelet, (iii) lack of requirement for laboratory monitoring or dose-titration, and (iv) the ability to exert its effect through a moiety with a short half-life, which limits extra-platelet effects. 2 Despite its proven efficacy, however, aspirin is a relatively weak antiplatelet drug, as shown by persistent platelet activation and aggregation in patients taking aspirin. 3 Some patients treated with aspirin also achieve less than expected inhibition of platelet function, a phenomenon that has been termed ‘aspirin resistance’. 4 Aspirin resistance has been associated with an increased risk of atherothrombotic vascular events. 4

Recognition of the central role of platelets in atherothrombotic vascular disease and the need for more effective inhibition of platelet function has led to the development of new antiplatelet agents. These agents exert their antithrombotic effect by targeting a platelet receptor or a platelet enzyme or both. The focus of this chapter will be on oral antiplatelet agents that are in active development for prevention and treatment of coronary artery disease and that target platelet receptors.