The Thienopyridines

Platelet adhesion, activation, and aggregation are key processes in the pathogenesis of coronary disease. Inhibition of these processes forms the cornerstone of therapy for coronary artery disease and particularly of acute coronary syndromes (ACS). Aspirin was the only available antiplatelet therapy for over 100 years, and it improves clinical outcome in a wide range of clinical situations. However, aspirin only inhibits platelet activation mediated by thromboxane A2, allowing platelet activation to occur through innumerable other pathways. As a result, adverse ischemic events are common when aspirin alone is used for the treatment of coronary disease, including ACS, during coronary interventions (particularly during stent implantation), and following coronary vascular brachytherapy (VBT). In these clinical situations, the presence of either thrombus, deep injury to the vessel wall, or delayed vascular reendothelialization leads to intense and often prolonged platelet activation, overwhelming the relatively weak effects of aspirin. The development of the thienopyridines, a class of antiplatelet drugs that reduce adenosine diphosphate‐ (ADP) mediated platelet activation, has significantly improved clinical outcomes in many coronary conditions. Widespread use of ticlopidine, the first available thienopyridine, was limited by frequent side‐effects, including life‐threatening neutropenia and thrombotic thrombocytopenic purpura. Following the introduction of clopidogrel, a thienopyridine with an excellent safety profile, dual antiplatelet therapy with aspirin and clopidogrel has become standard therapy following coronary stent implantation and coronary VBT. In patients presenting with ACS, the addition of clopidogrel to aspirin has now been proven to reduce ischemic events. The most important limitation of dual antiplatelet therapy is the increased bleeding risk as compared with aspirin alone, particularly in patients undergoing coronary artery bypass grafting during the index hospitalization. However, for many patients with ACS, combination therapy is appropriate.