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New Thrombin Antagonist for Acute Coronary Syndrome

Darrell Hulisz, RPh, PharmD
Beth Cuiksa, Doc

August 4, 2014

Vorapaxar (Zontivity®) is a protease activated receptor (PAR) type I (thrombin receptor) antagonist that has been approved by the FDA for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). Vorapaxar has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization in patients who are post-MI or have been diagnosed with PAD.¹ Vorapaxar decreases thrombotic events by binding to the PAR I receptor to block thrombin binding and prevent activation of the clotting cascade. Vorapaxar has only been studied in combination with aspirin 81mg orally once daily or clopidogrel (Plavix®) 75mg orally once daily as an adjunct therapy, to target the clotting cascade from multiple angles in secondary prevention populations. Vorapaxar has not yet been studied as an adjunct to other therapies such as warfarin (Coumadin®), dabigatran (Pradaxa®), or rivaroxaban (Xarelto®).

Patients who are prescribed vorapaxar should take one 2.5mg tablet orally once daily in addition to their aspirin or clopidogrel therapy. Vorapaxar does not need to be taken with regards to food and does not require renal dosage adjustment. It is currently contraindicated in patients who have a history of CNS bleeding, such as stroke or TIA, as well as history of stomach or intestinal ulcers. Vorapaxar most commonly causes anemia, depression, and rash. There is no reversal agent for vorapaxar toxicity. Dialysis and platelet transfusion have not been proven effective as reversal methodologies. Vorapaxar is classified as a Pregnancy Category B drug for use in pregnancy.

In studies of patients who have had an MI or PAD, this drug lowered the combined risk of MI, stroke and cardiovascular death. In the study that supported the drug's approval, vorapaxar lowered this risk from 9.5% to 7.9% over a 3-year period, or approximately 0.5% per year.²