New Therapy UpdateVorapaxar A Protease-Activated Receptor Antagonist for the Prevention of Thrombotic EventsLam, Sum PharmD*†; Tran, Tran PharmD*‡Author Information From the *Department of Clinical Health Professions, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY; †Divisions of Geriatric Medicine and Pharmacy, Winthrop University Hospital, Mineola, NY; and ‡Department of Pharmacy, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, NY. Disclosure: The authors declare no conflict of interest. Correspondence: Sum Lam, PharmD, Department of Clinical Health Professions, College of Pharmacy and Health Sciences, St. John’s University, St. Albert’s Hall, Room 114, 8000 Utopia Parkway, Queens, NY 11439. E-mail: firstname.lastname@example.org. Cardiology in Review: September/October 2015 - Volume 23 - Issue 5 - p 261-267 doi: 10.1097/CRD.0000000000000075 Buy Metrics Abstract Antiplatelet therapy reduces the risks for cardiovascular morbidity and mortality in patients with atherosclerotic disease, and it is also beneficial in managing peripheral arterial disease (PAD). These agents work through various therapeutic pathways to achieve antithrombotic effects. Although single- or two-drug regimens have been deployed to prevent vascular events, approximately 10% of the patients with acute coronary syndrome remain at risk for recurrent thrombotic events and may need a more aggressive preventative strategy. Vorapaxar offers a unique mechanism for platelet inhibition via the antagonism of protease-activated receptor-1. It is approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or PAD. This new drug approval was mainly based on the results from subgroup analyses from a large landmark trial (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events—Thrombolysis in Myocardial Infarction 50), which found that vorapaxar reduces the rate of the combined end point of cardiovascular death, MI, stroke, and urgent coronary revascularization when used in addition to aspirin and/or clopidogrel in patients without a history of stroke. In this study, vorapaxar was discontinued in patients with a history of stroke due to excessive risk for intracranial hemorrhage after 2 years of therapy. As an adjunctive therapy to standard regimens, vorapaxar provides a greater net clinical benefit in MI patients who are at a lower risk for bleeding. In patients with PAD, it reduces the rates of recurrent acute limb ischemia with rehospitalization or peripheral revascularization. The most concerning adverse effect is bleeding. Vorapaxar should not be used in patients with a history of stroke, transient ischemic attack, intracranial hemorrhage, or active pathological bleeding. The risks and benefits of adding vorapaxar to intensify antiplatelet regimens should be assessed in individual patients to aim for additional therapeutic outcomes with minimal bleeding risks. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.