Vorapaxar added to dual antiplatelet therapy (DAPT) reduced platelet-mediated thrombogenicity without affecting clot kinetics in patients with and without type 2 diabetes mellitus (DM), but platelet-mediated thrombogenicity was increased after aspirin withdrawal, particularly in patients with DM. The findings from the OPTIMUS-5 study were presented Sept. 1 as a moderated poster at ESC Congress 2019 and simultaneously published in JACC: Basic to Translational Science.

The objective of the prospective, parallel-design, open-label OPTIMUS-5 study was to evaluate the pharmacodynamic effects of vorapaxar added to standard-of-care DAPT (aspirin 81 mg once daily and clopidogrel 75 mg once daily) as well as the pharmacodynamic impact of discontinuing aspirin in patients with and without type 2 DM with prior myocardial infarction or peripheral arterial disease.

In the single-center study, the patients received vorapaxar (2.5 mg once daily) in addition to DAPT (triple therapy) for 30±5 days. The patients then stopped aspirin and continued dual therapy with vorapaxar and clopidogrel for 30±5 days. The primary endpoint was the comparison of CAT-induced maximum platelet aggregation (MPA) between the triple therapy and dual therapy groups. Noninferiority was assessed using a 95 percent confidence interval [CI] of the difference in MPA between the DM and non-DM arms.

The pharmacodynamic analysis population consisted of 64 patients who had received at least one dose of vorapaxar, 30 with DM and 34 without DM; of these, 28 patients in each arm had valid primary endpoint data. Vorapaxar added to DAPT resulted in complete blockade of TRAP-induced platelet aggregation (p<0.001) in both arms, which persisted after aspirin discontinuation. Vorapaxar did not affect markers of clot kinetics.

Vorapaxar added to DAPT significantly reduced CAT-induced aggregation in both arms (p<0.001). Stopping aspirin was associated with increased CAT-induced aggregation in patients with DM (p=0.010) and without DM (p=0.003). Thus, the noninferiority of the primary endpoint was not met.

"These pharmacodynamic observations do not support any potential clinical advantage of dual therapy with vorapaxar and clopidogrel compared with standard of care DAPT with aspirin and clopidogrel, especially in patients with DM," concluded the authors.

Keywords: ESC 19, ESC Congress, Diabetes Mellitus

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