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

• Published in: Journal of stroke and cerebrovascular diseases Vol. 21; no. 4; pp. 318 - 324
• Main Authors: Shinohara, Yukito, Goto, Shinya, Doi, Masaki, Jensen, Peder
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2012
• Subjects: Aged; Atherothrombotic disease; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - prevention & control; Cardiovascular; Drug Therapy, Combination - methods; Female; Humans; ischemic stroke; Japan; Lactones - administration & dosage; Lactones - adverse effects; Male; Middle Aged; Neurology; PAR-1; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; protease-activated receptor antagonist; protease-activated receptor-1; Pyridines - administration & dosage; Pyridines - adverse effects; Receptor, PAR-1 - antagonists & inhibitors; Receptor, PAR-1 - physiology; Secondary Prevention; Stroke - drug therapy; Stroke - metabolism; Stroke - prevention & control; Treatment Outcome; vorapaxar; Japan; protease-activated receptor-1; Atherothrombotic disease; vorapaxar; PAR-1; protease-activated receptor antagonist; ischemic stroke
• ISSN: 1052-3057; 1532-8511; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2010.09.005

Vorapaxar, formerly SCH 530348, is a novel, orally active, potent thrombin receptor inhibitor selective for the protease-activated receptor-1 (PAR-1). Previous phase II 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. 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 (75-150 mg/day). The primary endpoint was overall incidence of adverse events during the protocol-defined treatment phase (60 days). 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. Vorapaxar used in combination with standard doses of aspirin was safe and well tolerated in Japanese subjects with a history of ischemic stroke.