OPTIMUS-3 (Optimizing anti-Platelet Therapy In diabetes MellitUS)

18 Mar, 14

OPTIMUS-3

Background

Patients with diabetes have increased platelet reactivity, reduced platelet response to clopidogrel and higher risk of clinical events on clopidogrel vs patients without diabetes
Prasugrel, a more potent antiplatelet agent, is associated with greater reduction in ischaemic events compared to clopidogrel, particularly in patients with diabetes: TRITON subgroup analysis
However, there is no prospectively defined trial with well-characterized diabetes population which has compared the benefits of prasugrel with clopidogrel

Aim

To compare the pharmacodynamic activity of standard dose prasugrel vs high-dose clopidogrel in patients with diabetes

Study Design

Prospective, randomized, double-blind, two-period crossover study

Study Patient

Diabetes mellitus patients with coronary artery disease (N = 35)

Study Treatment

Patients were randomized to prasugrel 60 mg loading dose/10 mg maintenance dose & clopidogrel 600 mg loading dose/150 mg maintenance dose over two 1-week treatment periods separated by washout period of 2 weeks
Throughout the study, patients continued taking their pre-study dosage of aspirin

Efficacy Parameters

Platelet function: Assessed by 3 tests - VerifyNow P2Y12 assay, light transmission aggregometry (LTA), and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) at 0, 1, 4, and 24 hrs and 7 days (24 hrs after the last maintenance dose) after loading dose

Results

Prasugrel exhibited significantly greater inhibition of platelet aggregation by VerifyNow P2Y12 (89.3%) (primary endpoint) vs clopidogrel (27.7%) at 4 hrs post loading dose; superiority of prasugrel was maintained through 7 days

Difference in platelet inhibition by VerifyNow P2Y12 PRU was also significantly and consistently superior with prasugrel vs clopidogrel from 1 h through 7 days

Similar results were obtained using other platelet function measures
Significantly fewer poor responders at all time points, irrespective of definition used, were observed with prasugrel compared to clopidogrel

Safety

Major or minor bleeding by TIMI criteria did not occur in both treatment groups
Incidence of adverse events was 14.7% with prasugrel vs 25.7% with clopidogrel

Standard-dose prasugrel was associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods vs double-dose clopidogrel in patients with type 2 diabetes and coronary artery disease.

Thus, prasugrel may be a more appropriate antiplatelet agent than high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease.

Eur Heart J. 2011 Jan 20. [Epub ahead of print]