A Pharmacodynamic Comparison of Prasugrel vs. High-Dose Clopidogrel in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: Results of the Optimizing anti-Platelet Therapy In Diabetes MellitUS (OPTIMUS)-3 Trial

Eur Heart J. 2011 Apr;32(7):838-46. doi: 10.1093/eurheartj/ehq494. Epub 2011 Jan 20.

Abstract

Aims: Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM.

Methods and results: Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n= 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7%, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used.

Conclusion: In patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel.

Trial registration: ClinicalTrials.gov NCT00642174.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aspirin / therapeutic use
  • Clopidogrel
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / drug therapy*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Angiopathies / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Prasugrel Hydrochloride
  • Prospective Studies
  • Thiophenes / administration & dosage*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome
  • Young Adult

Substances

  • Piperazines
  • Platelet Aggregation Inhibitors
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00642174