Introduction: Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events due to their prothrombotic milieu and reduced response to antiplatelet agents, including clopidogrel. Prasugrel and ticagrelor have more prompt and potent antiplatelet effect than clopidogrel. However, limited data exist on the impact of DM status on the pharmacodynamic (PD) effects of these agents.
Methods: We conducted a post-hoc analysis of a prospective randomized PD study (n=110) investigating the effects of prasugrel vs ticagrelor after switching from clopidogrel among DM patients with coronary artery disease. Overall, 55 patients were randomized to prasugrel (20 DM, 35 no-DM) and 55 to ticagrelor (22 DM, 33 no-DM). PD assessments included P2Y12 reaction units (PRU) by VerifyNow and platelet reactivity index (PRI) by VASP assessed at 4 time points: baseline (on clopidogrel), 30 min and 2h after loading dose (LD) and after 1 week of maintenance dose (MD) treatment.
Results: Overall, platelet reactivity was higher in DM than in non-DM patients while on clopidogrel therapy. There were no differences between prasugrel and ticagrelor at any time point in both DM and non-DM patients. After switching to prasugrel, PRU was higher in DM vs non-DM patients post LD, whereas no significant difference was shown at 7 days (Panel A); PRI showed a similar trend but the difference was not significant (Panel B). After switching to ticagrelor, PRU was significantly higher in DM vs non-DM at 30 min and 7 days, with a trend at 2 h (Panel C); PRI was numerically higher in DM patients at 30 min with no difference at the other time points (Panel D).
Conclusions: Compared with clopidogrel, prasugrel and ticagrelor consistently reduce platelet reactivity to a similar extent irrespective of DM status. However, levels of platelet reactivity tend to remain higher with prasugrel and ticagrelor among DM patients supporting the hyper-reactive platelet phenotype which characterizes these patients.