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.