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.
Department of Emergency Medicine, Pennsylvania Hospital, Philadelphia, PA 19107, USA. pollackc@pahosp.com
Charles V
CV
Pollack
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D000241:Adenosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000284:Administration, Oral; D001241:Aspirin / Q000627:therapeutic use; D002309:Cardiology / Q000639:trends*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D004635:Emergency Medicine / Q000639:trends*; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D020445:Hospitalists / Q000639:trends; D006801:Humans; D007097:Imines / Q000627:therapeutic use; D007783:Lactones / Q000627:therapeutic use; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
C540445:E 5555; D007097:Imines; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D011725:Pyridines; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin; C530299:vorapaxar