Vorapaxar new drug update edited

New Drug Update: Vorapaxar Sara Ateeqi, Pharm.D., Bernard J. Dunn School of Pharmacy, Shenandoah University Jessica Crow, Pharm.D., BCPS, CNSC Vorapaxar (Zontivity™) was approved by the FDA in May 2014 for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). The vorapaxar labeling includes a black box warning that this medication increases the risk of bleeding, including intracranial hemorrhage (ICH) and fatal bleeding, and is contraindicated in patients with a history of stroke, transient ischemic attack (TIA), or ICH. Vorapaxar is a first-in-class proteaseactivated receptor-1 (PAR-1) antagonist that inhibits thrombin-induced platelet aggregation.1 In a large, phase III, double-blind, placebo-controlled trial, patients with a history of MI, ischemic stroke, or peripheral artery disease were randomized to vorapaxar 2.5 mg by mouth daily or placebo. Treatment was initiated a minimum of two weeks after the occurrence of MI or stroke. The primary end point was the composite of death from cardiovascular causes, MI, and stroke. At three years, the primary endpoint was significantly reduced in patients receiving vorapaxar compared to placebo (9.3 vs. 10.5%, HR 0.87; 95% CI 0.80-0.94; p=0.001). In a subgroup analysis, vorapaxar significantly reduced the primary endpoint in patients with a history of MI (HR 0.82; 95% CI 0.74 to 0.90; p<0.001).2 While vorapaxar showed a moderate benefit in reduction of major adverse cardiovascular events, it also significantly increased the risk of Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding and Thrombolysis in Myocardial Infarction (TIMI) clinically significant bleeding. There was also a significant increase in the rate of intracranial hemorrhage (ICH) in patients receiving vorapaxar (1 vs. 0.5%; p<0.001).2 Though statistically significant benefit was evident, when excluding patients with a history of stroke, the number needed to treat was 83 patients compared to the number needed to harm of 67 patients. Therefore, clinicians should carefully evaluate each patient for the risk of major bleeding versus the benefit of decreased major adverse cardiovascular events.

Vorapaxar was also studied in patients with acute coronary syndrome, but it failed to reduce the primary composite endpoint and significantly increased the risk of major bleeding, including ICH.3 Therefore, treatment should only be initiated in patients a minimum of two weeks after myocardial infarction.

1. Merck Statement on FDA Advisory Committee for Vorapaxar, Merck’s Investigational Antiplatelet Medicine. Merck. Retrieved 6 March 2014.

2. Morrow DA, et al. Vorapaxar in the Secondary Prevention of Atherothrombotic Events. N Engl J Med. 2012;366:1404-13 3. Tricoci P, et al. Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes. N Engl J Med 2012;366: 20-33.