Abstract 527: Vorapaxar Does Not Increase Bleeding Time

2016 
Vorapaxar is a novel PAR-1 inhibitor approved in the US and EU to reduce risk of thrombotic CV events in patients with a history of MI, and in the US also in patients with PAD. It does not affect coagulation tests (TT, PT, aPTT, ACT, ECT). Aspirin and P2Y 12 inhibitors prolong human bleeding time (BT); does vorapaxar? Methods: In this randomized, active controlled, parallel group, 2-period, single-blind, open-label trial, healthy men (n=31) and women (n=5), in Period 1, received either 81 mg aspirin (ASA) QD for 7 days (N=18), or a 7 day regimen of vorapaxar (N=18) achieving steady state plasma concentrations equivalent to chronic 2.5 mg QD doses. In Period 2, each group added 7 days of the therapy alternate to that of Period 1 without washout. BT and platelet aggregation (PA) using arachidonic acid, ADP, and TRAP agonists were collected predose in Periods 1 (baseline) and 2, and 24 h after Period 2 last dose. A linear mixed effects model with fixed effect for treatment analyzed data. Results: BT geometric mean ratio (90% CI) for (vorapaxar/baseline) was 1.01 (0.88, 1.15), (ASA/baseline) was 1.32 (1.15, 1.51), (vorapaxar+ASA/vorapaxar) was 1.47 (1.26, 1.70), (vorapaxar+ASA/ASA) was 1.12 (0.96, 1.30). Each antiplatelet inhibited PA only as expected. See figure. Conclusions: Unlike ASA, vorapaxar did not prolong BT compared to baseline. When given with ASA, there is a slight numerical increase in BT beyond that of ASA. Implications for clinical spontaneous or surgical bleeding await further analyses of clinical trial data.
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