Dataset Information

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

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).

SUBMITTER: Franchi F

PROVIDER: S-EPMC6978557 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Franchi Francesco F Rollini Fabiana F Kairouz Victor V Rivas Rios Jose J Rivas Andrea A Agarwal Malhar M Briceno Maryuri M Wali Mustafa M Nawaz Ahmed A Silva Gabriel G Shaikh Zubair Z Maaliki Naji N Been Latonya L Piraino Jason J Pineda Andres M AM Suryadevara Siva S Soffer Daniel D Zenni Martin M MM Jennings Lisa K LK Bass Theodore A TA Angiolillo Dominick J DJ

JACC. Basic to translational science 20190901 7

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 wi ...[more]

PMID: 31998847

Similar Datasets

Project description:Background Vorapaxar as an adjunct to dual antiplatelet therapy (DAPT) reduces thrombotic events in patients with prior myocardial infarction at the expense of increased bleeding. Withdrawal of aspirin has emerged as a bleeding reduction strategy. The pharmacodynamic effects of vorapaxar with potent P2Y12 inhibitors as well as the impact of dropping aspirin is unexplored and represented the aim of the VORA-PRATIC (Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y12 Receptor Inhibitors Prasugrel and Ticagrelor) study. Methods and Results Post-myocardial infarction patients (n=130) on standard DAPT (aspirin+prasugrel or ticagrelor) were randomized to 1 of 3 arms: (1) triple therapy: aspirin+prasugrel/ticagrelor+vorapaxar; (2) dual therapy (drop aspirin): prasugrel/ticagrelor+vorapaxar; (3) DAPT: aspirin+prasugrel/ticagrelor. Pharmacodynamic assessments were performed at 3 time points (baseline and 7 and 30 days). Vorapaxar reduced CAT (collagen-ADP-TRAP)-induced platelet aggregation, a marker of platelet-mediated global thrombogenicity (triple therapy versus DAPT at 30 days: mean difference=-27; 95% CI,-35 to -19; P<0.001; primary end point). This effect was attenuated but still significant in the absence of aspirin (dual therapy versus DAPT at 30 days: mean difference=-15; 95% CI,-23 to -7; P<0.001; between-group comparisons, P<0.05). Vorapaxar abolished TRAP-induced aggregation (P<0.001), without affecting thrombin generation and clot strength. There were no differences in markers of P2Y12 reactivity. Markers sensitive to aspirin-induced effects increased (P<0.001) in the dual-therapy arm. Conclusions In post-myocardial infarction patients treated with potent P2Y12 inhibitors, vorapaxar reduces platelet-driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin and without affecting markers of P2Y12 reactivity or clot kinetics. The clinical implications of these PD observations warrant future investigation. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02545933.

Project description:Background: Diabetes mellitus (DM) has a high morbidity and mortality worldwide, and it is a risk factor for cardiovascular diseases. Non-diabetic stress hyperglycemia is common in severely ill patients, and it could affect prognosis. This study aimed to analyze the influence of different blood glucose levels on prognosis from the perspective of stress hyperglycemia by comparing them with normal blood glucose levels and those of patients with DM. Methods: A retrospective study of 1,401 patients in coronary care unit (CCU) from the critical care database called Medical Information Mart for Intensive Care IV was performed. Patients were assigned to the following groups 1-4 based on their history of DM, random blood glucose, and HbA1c levels: normal blood glucose group, moderate stress hyperglycemia group, severe stress hyperglycemia group and DM group. The main outcome of this study was 30- and 90-day mortality rates. The associations between groups and outcomes were analyzed using Kaplan-Meier survival analysis, Cox proportional hazard regression model and competing risk regression model. Results: A total of 1,401 patients in CCU were enrolled in this study. The Kaplan-Meier survival curve showed that group 1 had a higher survival probability than groups 3 and 4 in terms of 30- and 90-day mortalities. After controlling the potential confounders in Cox regression, groups 3 and 4 had a statistically significant higher risk of both mortalities than group 1, while no difference in mortality risk was found between groups 2 and 1. The hazard ratios [95% confidence interval (CI)] of 30- and 90-day mortality rates for group 3 were 2.77(1.39,5.54) and 2.59(1.31,5.12), respectively, while those for group 4 were 1.92(1.08,3.40) and 1.94(1.11,3.37), respectively. Conclusions: Severe stress hyperglycemia (≥200 mg/dL) in patients without DM in CCU may increase the risk of short-term death, which is greater than the prognostic effect in patients with diabetes. Patients with normal blood glucose levels and moderate stress hyperglycemia (140 mg/dL ≤ RBG <200 mg/dL) had no effect on short-term outcomes in patients with CCU.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets