New Drugs and Technologies

1287 Patients with a history of heart disease are at increased risk for future cardiovascular events, including myocardial infarction (MI), stroke, and death resulting from cardiovascular disease. Although coronary artery disease remains the leading cause of mortality worldwide, advancements in medical therapy, particularly antithrombotic agents, have improved patient outcomes. Although the trend for MI and death after acute coronary syndrome (ACS) over the past 20 years has declined, such medical advancements are still met with discouraging rates of death and MI after revascularization. To this end, it is the recommendation of the American College of Cardiology and American Heart Association that all ACS patients, regardless of whether percutaneous coronary intervention was performed, be treated with dual antiplatelet therapy (DAPT) for 1 year (Class IA). Such recommendations are based largely on results from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which assessed aspirin versus DAPT with aspirin and clopidogrel for the reduction of ischemic end points in patients presenting with non–ST-segment–elevation ACS who did not receive percutaneous coronary intervention. Seeing a need for further risk reduction in long-term management of patients with established atherothrombotic risk, the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2P)–Thrombolysis in Myocardial Infarction (TIMI) 50 was conducted. The study drug, vorapaxar (Zontivity, Merck, NJ), is an antagonist of the platelet protease-activated receptor (PAR-1) and inhibits thrombin-induced platelet aggregation. Vorapaxar was shown to have a significant benefit for the reduction of cardiovascular death and ischemic complications in addition to secondary prevention. Vorapaxar was also tested in the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial as part of adjunct therapy in the non–ST-segment–elevation ACS population. In this population, however, the increased risk of bleeding outweighed the potential reduction of atherothrombotic events. Thus, Merck (the sponsor) presented efficacy and safety data from both trials to the US Food and Drug Administration’s (FDA’s) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) on January 15, 2014, in Silver Spring, MD. The CRDAC was asked to opine on the approvability of vorapaxar for the reduction of atherothrombotic events in patients with a history of MI, notwithstanding the concerns for the subgroup populations, which showed increased rates of intracranial hemorrhage (ICH), including patients with a previous history of stroke or body weight <60 kg.