Emerging Oral Antiplatelet Therapies for Acute Coronary Syndromes

Emergency department physicians, along with hospitalists and interventional cardiologists, provide first-line care for patients experiencing symptoms potentially associated with acute coronary syndromes (ACS). Because these health care providers encounter and manage patients with varying degrees of risk, a clear understanding of the modes of action, benefits, and limitations of various therapeutic options is crucial for achieving optimal outcomes in the acute-care setting. Oral antiplatelet therapy has a major role in the acute care of patients with suspected ACS due to the critical role of platelets in the pathophysiology of disease. The current standard-of-care oral antiplatelet therapy for ACS is aspirin in combination with a P2Y12 adenosine diphosphate (ADP) receptor antagonist, most commonly clopidogrel. Aspirin and P2Y12 antagonists have both demonstrated efficacy in reducing morbidity and mortality in patients with ACS, but are also associated with increased bleeding risk compared with controls. Additionally, despite dual oral antiplatelet therapy, patients remain at substantial residual risk for ischemic events due to thrombotic episodes driven by platelet activation pathways that are not inhibited by these agents, including the protease-activated receptor (PAR)-1 platelet activation pathway, stimulated by thrombin. Novel oral antiplatelet agents in advanced clinical development include a direct and more readily reversible P2Y12 antagonist, ticagrelor, as well as a new class of PAR-1 antagonists, which includes vorapaxar and atopaxar. Ticagrelor has shown a significant ischemic benefit and an increase in non-surgical bleeding over clopidogrel in the large phase 3 Platelet Inhibition and Patient Outcomes trial. Results of phase 2 trials with PAR-1 antagonists suggest that these agents may provide incremental reduction in ischemic events without a bleeding liability. This hypothesis is being evaluated in 2 large ongoing phase 3 trials with vorapaxar, including the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA*CER) trial in patients with non-ST-segment elevation ACS.