Abstract 4946: Comparison of Prasugel With Clopidogrel on Platelet Function in Coronary Artery Disease Patients With Type 2 Diabetes Mellitus - Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3)
Introduction: Type 2 diabetes mellitus (T2DM) patients (pts) have decreased response to clopidogrel (Clop) compared to non-diabetic patients. Prasugrel (Pras) has shown to be more efficacious than Clop in reducing thrombotic cardiovascular events in T2DM pts with acute coronary syndrome undergoing percutaneous coronary interventions. However, the pharmacodynamic effects of Pras compared to Clop in T2DM have not been fully explored. The OPTIMUS-3 study evaluated pharmacodynamic responses of Pras compared with Clop in coronary artery disease (CAD) pts with T2DM.
Methods: A total of 35 CAD pts with T2DM on chronic aspirin were randomized to Pras 60 mg loading dose (LD)/10 mg maintenance dose (MD) or Clop 600 mg LD/150 mg MD for 1 week in a double-blind cross-over design with a 2 week washout period between study drugs. Platelet function was assessed by the VerifyNow P2Y12 (VN-P2Y12) assay, light transmission aggregometry (LTA) following 5 and 20 μM ADP, and phosphorylation of vasodilator stimulated phosphoprotein (VASP), at baseline, 1 hr, 4 hr and 24 hr post LD, and 6 – 8 days post-MD. The primary comparison of inhibition of platelet aggregation (IPA) at 4 hours after LD between 60 mg Pras and 600 mg Clop was assessed by VN-P2Y12.
Results: Significantly greater IPA by VN-P2Y12 at 4 hr post LD was achieved by Pras vs. Clop (89.3 % vs. 27.7%, p<0.0001). Significantly greater IPA was also observed at 1 hr and 24 hr post LD and 7 days post-MD (Figure⇓). Similar results were obtained when platelet function was assessed by VN-P2Y12 Reaction Units, LTA and VASP.
Conclusion: In CAD pts with T2DM, Pras is associated with significantly greater inhibition of platelet function than high LD and MD regimens of Clop.