Safety and exploratory efficacy of the novel thrombin receptor (PAR-1) antagonist SCH530348 for non-ST-segment elevation acute coronary syndrome.
OBJECTIVE
A previous phase 2 study of patients undergoing non-urgent PCI treated with SCH530348 plus aspirin and clopidogrel tended to reduce MACE without increased bleeding. This study evaluated the safety of SCH530348 in Japanese patients with NSTE ACS.


METHODS
Subjects (117), in whom PCI was planned, received standard-of-care (aspirin, ticlopidine, and heparin) and were randomized 4:1 to receive either SCH530348 (20 or 40 mg loading dose followed by 1 mg/d or 2.5 mg/d for 60 days) or placebo. The key safety endpoint was TIMI major and minor bleeding in the PCI cohort (n=92). The key exploratory efficacy endpoint was MACE and death within 60 days. Addition of SCH530348 to standard-of-care did not significantly increase the rate of TIMI major and minor bleeding (or non-TIMI bleeding) in the primary cohort.


RESULTS
Incidence (non-MACE) and discontinuation of AEs were similar across groups. PCI subjects treated with SCH530348 plus standard-of-care experienced a significant reduction in periprocedural MI compared with standard-of-care alone (16.9% vs 42.9%, respectively; p=0.013). There were no deaths or any other MACE.


CONCLUSIONS
SCH530348 added to standard-of-care did not result in excess bleeding in Japanese subjects with NSTE ACS but significantly reduced the incidence of periprocedural MI in subjects undergoing urgent PCI.
Goto
Shinya
S
Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan. sgoto3@mac.com
Yamaguchi
Tetsu
T
Ikeda
Yasuo
Y
Kato
Kenichi
K
Yamaguchi
Hiroya
H
Jensen
Peder
P
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007564:Japan; D007783:Lactones / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011725:Pyridines / Q000008:administration & dosage*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
D007783:Lactones; D010919:Placebos; D011725:Pyridines; D044463:Receptor, PAR-1; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; C530299:vorapaxar