Vorapaxar may reduce heart attack and stroke, but raises bleeding risk

Vorapaxar added to standard of care reduced the risk of cardiovascular events and stroke compared to standard of care alone, according to Merck, who announced top-line results of its TRA-2P (Thrombin Receptor Antagonist in Secondary Prevention of atherothrombotic ischemic events) study earlier this month. However, results also demonstrated that the drug was associated with a significant increase in bleeding, including intracranial hemorrhage (ICH).

Vorapaxar is an investigational oral Protease Activated Receptor 1 (PAR-1) thrombin receptor antagonist which Merck has developed for the prevention of thrombosis and the reduction of cardiovascular events.

The TRA-2P trial, which began in September 2007 and completed in December 2011, was designed to determine whether the addition of vorapaxar to standard of care for patients with a known history of heart attack, ischemic stroke, or peripheral artery disease would decrease the risk of heart attack and stroke compared with standard of care alone. The study also looked at whether vorapaxar, when added to standard of care, increased the risk of bleeding.

The results of TRA-2P follow the reported results of a study led by the Duke Clinical Research Institute, presented in 2011 at the American Heart Association Scientific Sessions and published in the January 5, 2012 issue of The New England Journal of Medicine. The study, called TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome), focused on whether the addition of vorapaxar to standard of care would better prevent heart attack and stroke in patients with acute coronary artery syndrome compared with standard of care alone. TRACER was halted at the recommendation of the data and safety monitoring board after an unplanned safety review demonstrated a non-significant reduction in its primary end points. At the same time, it was recommended that the company discontinue the treatment for patients in the TRA-2P study who had previously experienced a stroke.

The full results of TRA-2P will be presented at the American College of Cardiology Scientific Sessions this month, and Merck will continue to review the data from both trials.