Credit: Andre E.X. Brown
The US Food and Drug Administration (FDA) has approved the antiplatelet agent vorapaxar (Zontivity) to reduce the risk of thrombotic cardiovascular events in patients with a history of myocardial infarction or peripheral arterial disease.
Results of a large study suggested the drug can be effective as prophylaxis but may also increase the risk of bleeding.
Vorapaxar’s label has a black box warning describing this risk, which includes intracranial hemorrhage and fatal bleeding.
The warning also states that vorapaxar should not be given to patients with a history of stroke, transient ischemic attack, intracranial hemorrhage, or active pathological bleeding.
The drug will be dispensed with an FDA-approved patient medication guide that provides instructions for its use and important safety information.
Vorapaxar tablets are intended to be given once daily, along with aspirin and/or clopidogrel, according to their indications or the standard of care.
“In patients who have had a heart attack or who have peripheral arterial disease, this drug will lower the risk of heart attack, stroke, and cardiovascular death,” said Ellis Unger, MD, director of the Office of Drug Evaluation in the FDA’s Center for Drug Evaluation and Research.
“In the study that supported the drug’s approval, [vorapaxar] lowered this risk from 9.5% to 7.9% over a 3-year period—about 0.5% per year.”
The study, which was published in NEJM, included 26,449 patients with a history of myocardial infarction (n=17,779), ischemic stroke (n=4883), or peripheral arterial disease (n=3787).
The patients were randomized to receive vorapaxar at 2.5 mg daily or matching placebo, in addition to standard antiplatelet therapy.
The study’s primary efficacy endpoint was the composite of death from cardiovascular causes, myocardial infarction, or stroke. At 3 years, 1028 patients (9.3%) in the vorapaxar group and 1176 patients (10.5%) in the placebo group reached the primary endpoint.
Both moderate and severe bleeding events were significantly higher in patients on vorapaxar than in the placebo group. Bleeding occurred in 4.2% and 2.5% of patients, respectively. And intracranial hemorrhage occurred in 1.0% and 0.5%, respectively.
The risk of intracranial bleeding was highest among patients with a history of stroke, so these patients were taken off of vorapaxar early.
Vorapaxar is made by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., of Whitehouse Station, New Jersey. For more information on the drug, see the full prescribing information.
