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.