Progress in platelet medicine: focus on stent thrombosis and drug resistance

Abstract

The outcome importance of coronary stent thrombosis has mandated the careful management of these devices and their associated platelet blockade during the perioperative period. Recent trials have highlighted the catastrophic outcomes after stent thrombosis. The maintenance of clinically effective platelet blockade not only is essential to prevent stent thrombosis but also to optimize outcome in the integrated management of acute coronary syndromes. Dual antiplatelet blockade with aspirin and clopidogrel must balance the risks of ischemia and bleeding in patients with acute coronary syndromes, especially in the subset who require urgent surgical coronary revascularization. Platelet resistance to thienopyridines such as clopidogrel and prasugrel may be a significant risk factor for adverse cardiovascular outcomes. This phenomenon is detectable by point-of-care assays although standardized definitions and standardized testing batteries have yet to be formulated. The determinants of platelet resistance to thienopyridine therapy include genetic polymorphisms (especially related to hepatic drug metabolism) and drug interactions (especially the proton pump inhibitors). Novel platelet blockers are currently in late clinical development and will likely induce more consistent platelet blockade because of pharmacokinetic advantages including the lack of hepatic metabolism for activation. These agents will likely supersede clopidogrel and prasugrel if randomized trials show superior efficacy and clinical safety.