Vorapaxar reduces CV events but may increase bleeding
MedWire News: Researchers have found that vorapaxar, a novel selective thrombin inhibitor, reduces the risk for cardiovascular (CV) death or ischemic events in patients with stable atherosclerosis already on aspirin therapy.
Patients with a history of myocardial infarction (MI) were found to derive the greatest benefit, but the drug was also found to increase the risk for moderate or severe bleeding, including intracranial hemorrhage.
In total, 26,449 patients with a history of MI, ischemic stroke, or peripheral arterial disease were randomly assigned to treatment with vorapaxar (2.5 mg daily) or placebo. The majority (94%) of patients were on aspirin therapy during the study period.
After 24 months of treatment, the data and safety monitoring board recommended discontinuation of vorapaxar among patients with a history of stroke as a result of numerous reports of intracranial hemorrhage in this patient subgroup.
At 3 years, a significantly lower percentage of patients treated with vorapaxar reached the primary composite endpoint of CV death, MI, or stroke compared with those assigned to placebo (9.3 vs 10.5%; hazard ratio [HR]=0.87).
Furthermore, among patients with no history of stroke who received vorapaxar, the primary endpoint occurred in 8.3% compared with 9.6% of those treated with placebo (HR=0.84).
Patients who received vorapaxar were also significantly less likely than those on placebo to die from CV events or experience, MI, stroke, or recurrent ischemia leading to revascularization (11.2 vs 12.4%; HR=0.88).
Despite the encouraging findings, David Morrow (Brigham and Women's Hospital, Boston, Massachusetts, USA) and team found a greater incidence of moderate or severe bleeding among those who received vorapaxar compared with placebo (4.2 vs 2.5%; HR=1.66).
The incidence of intracranial hemorrhage was also found to be twofold greater among those treated with vorapaxar compared with placebo, at 1.0% versus 0.5%. This difference was found to be even larger between patients with a history of stroke treated with vorapaxar compared with placebo, at 2.4% versus 0.9%. However, the rate of fatal bleeding was similar between the groups.
"The reduction in cardiovascular events [with vorapaxar] came at the cost of increased bleeding. This benefit and risk emerged early and continued to accrue throughout follow-up," write the authors in TheNew England Journal of Medicine.
By Ingrid Grasmo