Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study

JACC Basic Transl Sci. 2019 Sep 1;4(7):763-775. doi: 10.1016/j.jacbts.2019.07.011. eCollection 2019 Nov.

Abstract

Vorapaxar reduces thrombotic cardiovascular events at the expense of increased bleeding. However, the differential pharmacodynamic (PD) effects of vorapaxar according to diabetes mellitus (DM) status are unknown. Moreover, although withdrawal of aspirin has emerged as a bleeding reduction strategy, the PD effects of stopping aspirin in patients treated with vorapaxar also are unknown. In this prospective PD investigation, vorapaxar was associated with reduced platelet-mediated thrombogenicity without affecting clot kinetics irrespective of DM status. However, platelet-mediated thrombogenicity increased after aspirin withdrawal, particularly among patients with DM. (Optimizing anti-Platelet Therapy In diabetes MellitUS-5 Study [OPTIMUS-5]; NCT02548650).

Keywords: ADP, adenosine diphosphate; CAT, collagen-related peptide + adenosine diphosphate + thrombin receptor activating peptide; CI, confidence interval; COX, cyclooxygenase; DAPT, dual antiplatelet therapy; DM, diabetes mellitus; LTA, light transmittance aggregometry; MI, myocardial infarction; MPA, maximum platelet aggregation; PAD, peripheral arterial disease; PAR, protease-activated receptor; PD, pharmacodynamic; TRAP, thrombin receptor activating peptide; TXB2, thromboxane B2; VASP, vasodilator-stimulated phosphoprotein; dual antiplatelet therapy; o.d., once daily; pharmacodynamics; platelets; thrombin; vorapaxar.

Associated data

  • ClinicalTrials.gov/NCT02548650