Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

Abstract

BACKGROUND:Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel. Whether these findings may be attributed to differences in the pharmacodynamic profiles of these drugs in DM patients remains poorly explored and represented the aim of this study. METHODS:In this prospective, randomized, double-blind, double-dummy, crossover pharmacodynamic study, aspirin-treated DM patients (n=50) with coronary artery disease were randomly assigned to receive prasugrel (60 mg loading dose [LD]/10 mg maintenance dose once daily) or ticagrelor (180 mg LD/90 mg maintenance dose twice daily) for 1 week. Pharmacodynamic assessments were conducted using 4 different assays, including VerifyNow P2Y12, vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate, which allowed us to explore ADP-and non-ADP-induced (arachidonic acid-, collagen-, thrombin receptor-activating, peptide-induced) platelet signaling pathways. The acute (baseline, 30 minutes, and 2 hours post-LD) and maintenance (1 week) effects of therapy were assessed. The primary end point of the study was the comparison of P2Y 12 reaction units determined by VerifyNow P2Y12 at 1 week between prasugrel and ticagrelor.RESULTS: ADP-and non-ADP-induced measures of platelet reactivity reduced significantly with both prasugrel and ticagrelor LD and maintenance dose. P2Y 12 reaction units defined by VerifyNow were similar between prasugrel and ticagrelor at 30 minutes and 2 hours post-LD. At 1 week, P2Y 12 reaction units were significantly lower with ticagrelor than with prasugrel (52 [32-72] versus 83 [63-103]; least-square means difference: -31; 95% confidence interval, -57 to -4; P=0.022; primary end point). Pharmacodynamic assessments measured by vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate were similar between prasugrel and ticagrelor at each time point, including at 1 week. Rates of high on-treatment platelet reactivity were similar between groups with all assays at all time points. CONCLUSIONS:In DM patients with coronary artery disease, ticagrelor exerts similar or greater inhibition of ADP-induced platelet reactivity in comparison with prasugrel in the acute and chronic phases of treatment, whereas the inhibition of measures of non-ADP-induced platelet reactivity was not significantly different between the 2 agents.

Incremental role of glycaemic variability over HbA1c in identifying type 2 diabetic patients with high platelet reactivity undergoing percutaneous coronary intervention

“…For instance, our study generates the hypothesis that periprocedural GV and HbA1c assessment may help to identify those diabetic patients that should be moved towards more aggressive antiplatelet management, such as ticagrelor, also in the setting of an elective procedure [35, 36].…”

The Effect of Diabetes on Prognosis Following Myocardial Infarction Treated with Primary Angioplasty and Potent Antiplatelet Therapy

“…Subjects with DM had a greater reduction in ischemic events without an increase in major bleeding and therefore had a greater net treatment benefit with prasugrel compared to patients without DM [ 12 ]. Ticagrelor exerts similar or greater inhibition of platelet reactivity compared to prasugrel in DM patients with coronary artery disease [ 15 ]. Therefore, we hypothesized that we would observe a less negative impact of DM on the prognosis of patients in PRAGUE-18 compared to older studies.…”

Effects of Thiazolidinedione and New Antidiabetic Agents on Stroke

“…Although the semaglutide trial showed significant beneficial effects on nonfatal stroke, the cardiovascular outcome trials were underpowered for the specific stroke endpoints. More studies using ertugliflozin (SGLT2 inhibitor) and dulaglutide (once-weekly GLP1 analogue) are currently ongoing in the hope of improving vascular outcomes and total mortality in patients with diabetes at high stroke risk [83,84]. Until the results of these studies are released, multifactorial interventions targeting individual cerebrovascular risk factors are required to improve clinical outcomes in diabetes patients after a stroke or at high risk of stroke.…”