Effect of Vorapaxar Alone and in Combination with Aspirin on Bleeding Time and Platelet Aggregation in Healthy Adult Subjects.
The effect of the protease-activated receptor-1 (PAR-1) antagonist vorapaxar on human bleeding time is not known. This was a randomized, two-period, open-label trial in healthy men (n = 31) and women (n = 5). In period 1, subjects received 81 mg aspirin q.d. or a vorapaxar regimen achieving steady-state plasma concentrations equivalent to chronic 2.5 mg q.d. doses, for 7 days. In period 2, each group added 7 days of the therapy alternate to that of period 1 without washout. Bleeding time and platelet aggregation using arachidonic acid, ADP, and TRAP agonists were assessed. Bleeding time geometric mean ratio (90% CI) for vorapaxar/baseline was 1.01 (0.88-1.15), aspirin/baseline was 1.32 (1.15-1.51), vorapaxar + aspirin/vorapaxar was 1.47 (1.26-1.70), and vorapaxar + aspirin/aspirin was 1.12 (0.96-1.30). Unlike aspirin, vorapaxar did not prolong bleeding time compared with baseline. Bleeding time following administration of vorapaxar with aspirin was similar to that following aspirin alone.
Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
W K
WK
Kraft
Merck & Co, Kenilworth, New Jersey, USA.
J H
JH
Gilmartin
Merck & Co, Kenilworth, New Jersey, USA.
D L
DL
Chappell
Merck & Co, Kenilworth, New Jersey, USA.
F
F
Gheyas
Merck & Co, Kenilworth, New Jersey, USA.
B M
BM
Walker
Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
S
S
Nagalla
Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
U P
UP
Naik
Merck & Co, Kenilworth, New Jersey, USA.
J C
JC
Horrow
Merck & Co, Kenilworth, New Jersey, USA.
R E
RE
Wrishko
Merck & Co, Kenilworth, New Jersey, USA.
S
S
Zhang
Merck & Co, Kenilworth, New Jersey, USA.
M S
MS
Anderson
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001760:Bleeding Time; D001780:Blood Coagulation Tests; D004359:Drug Therapy, Combination; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018179:Receptors, Thrombin / Q000819:agonists; D055815:Young Adult
D007783:Lactones; D011725:Pyridines; D018179:Receptors, Thrombin; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D001241:Aspirin; C530299:vorapaxar