Antiplatelet therapy in acute coronary syndrome (ACS): applying new science to clinical decisions.
The platelet is central to the pathogenesis of acute coronary syndromes (ACS), and antiplatelet therapy has demonstrated a significant reduction in the risk for ischemic events in patients with ACS. For patients with unstable angina or non-ST elevation myocardial infarctions, regardless of whether a conservative or invasive (i.e., percutaneous intervention) treatment approach is used, current guidelines recommend combination antiplatelet therapies, including aspirin with the thienopyridines clopidogrel or prasugrel and/or a glycoprotein IIb/IIIa inhibitor. However, there remains a significant incidence of arterial thrombosis in patients receiving currently available antiplatelet therapy, indicating the need for improved and/or alternative agents and targets. Recent landmark clinical trials of new oral antiplatelet therapies, including the thienopyridine prasugrel and the investigational reversible oral adenosine diphosphate antagonist ticagrelor, indicate they have a faster onset of action, result in a more predictable response, and provide improved efficacy compared to clopidogrel, the current standard of care. Other promising potential targets under investigation to reduce the contribution of the platelet to ACS pathophysiology include von Willebrand factor, thromboxane A(2), and protease-activated receptor-1. Of these, the protease-activated receptor-1 antagonist vorapaxar (SCH 530348) is furthest along in clinical development, with phase II data showing profound inhibition of platelet aggregation and a large phase III development program under way. A fundamental lingering issue is whether improved prevention and treatment of thrombosis can be separated from an increase in hemorrhage or bleeding, and clinicians must continue to consider the potential risks and benefits when individualizing antiplatelet therapy for patients with ACS.
Becker, RC; Gibson, CM; Jennings, LK; Morrow, DA
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