Abstract 1710: Platelet Function in Diabetes Mellitus: Observations From the PRINCIPLE-TIMI 44 Trial
Background: CV disease is a leading cause of morbidity and mortality in diabetes (DM). Patients (pts) with DM have increased platelet (plt) reactivity. Prasugrel, a 3rd generation thienopyridine, was shown in clinical studies to provide a greater clinical benefit overall, but particularly in DM pts compared to standard-dose clopidogrel in TRITON-TIMI 38. We examined the data from PRINCIPLE-TIMI 44 to determine the mechanistic underpinning of this finding.
Methods: Plt measures and clinical events among 201 pts who underwent a planned PCI including 62 with DM were analyzed. The trial compared prasugrel (60mg loading dose (LD)) followed by 10mg daily maintenance dose (MD) to higher dose clopidogrel (600mg LD followed by 150mg daily MD).
Results: With or without DM, pts on prasugrel had a consistently greater inhibition of plt aggregation (IPA) and reduced rates of maximal plt aggregation (MPA) at 6hrs post LD, and 15D MD (p < 0.01 for each). Poor response, prespecified as IPA with 20μmol/L ADP<20%, was less frequent in prasugrel vs clopidogrel pts (6hrs: 0.0% vs 27.3%, p < 0.0001; 15D: 2.5% vs 15.2%, p = 0.06). When stratified by treatment, clopidogrel diabetics had a greater nonresponse than prasugrel diabetics (Figure⇓). Among clopidogrel pts, those with DM tended to be more likely to have poor response than pts without DM (Figure⇓), though no difference was seen among prasugrel pts.
Conclusions: Among pts with DM, treatment with prasugrel resulted in higher levels of platelet inhibition and fewer poor responders. Among clopidogrel pts, the rate of poor response tended to be higher among pts with DM. These mechanistic observations may help to explain the benefit of prasugrel among pts with DM.