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 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.


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 (75-150 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.
Shinohara
Yukito
Y
Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital, Tokyo, Japan. yshinoha@tachikawa-hosp.gr.jp
Goto
Shinya
S
Doi
Masaki
M
Jensen
Peder
P
D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007564:Japan; D007783:Lactones / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D044463:Receptor, PAR-1 / Q000502:physiology; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D016896:Treatment Outcome
D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D044463:Receptor, PAR-1; C530299:vorapaxar