Safety of the Novel Protease-Activated Receptor-1 Antagonist Vorapaxar in Japanese Patients with a History of Ischemic Stroke

Background: Vorapaxar, formerly SCH 530348, is a novel, orally active, potent thrombin receptor inhibitor selective for the protease-activated receptor-1 (PAR-1). Previous phase 11 studies of patients undergoing urgent or scheduled percutaneous coronary intervention treated with vorapaxar plus aspirin and clopidogrel or ticlopidine showed a trend toward reducing major adverse cardiac events, particularly myocardial infarction, without increasing bleeding risk. The present study evaluated the safety of vorapaxar in Japanese patients with a history of ischemic stroke receiving aspirin. Methods: Ninety patients with previous ischemic stroke (>= 14 days to <1 year before randomization) were randomized to receive vorapaxar (1 or 2.5 mg) or placebo once daily for 60 days. All patients received aspirin (75150 mg/day). The primary endpoint was overall incidence of adverse events during the protocol-defined treatment phase (60 days). Results: Addition of vorapaxar to aspirin did not significantly increase the overall incidence of adverse events, including serious adverse events. None of the patients treated with vorapaxar plus aspirin experienced thrombolysis in myocardial infarction major or minor bleeding versus 1 patient treated with placebo. Nonfatal stroke occurred in 1 patient allocated to placebo and 1 patient allocated to vorapaxar. Conclusions: Vorapaxar used in combination with standard doses of aspirin was safe and well tolerated in Japanese subjects with a history of ischemic stroke.