Optimizing Antiplatelet Therapy in Diabetes Mellitus-4 - OPTIMUS-4

Contribution To Literature:

The OPTIMUS-4 trial showed that the pharmacodynamic profiles of prasugrel versus ticagrelor were largely similar among diabetics.


The goal of the trial was to compare pharmacodynamic profiles of prasugrel versus ticagrelor among patients with diabetes mellitus and coronary artery disease.

Study Design

  • Randomized
  • Parallel
  • Blinded

Patients with diabetes mellitus and coronary artery disease were randomized to a prasugrel 60 mg load/10 mg daily maintenance (n = 46) versus ticagrelor 180 mg load/90 mg twice daily maintenance (n = 46). This was a case-crossover design.

  • Total number of enrollees: 46
  • Duration of follow-up: 1 week
  • Mean patient age: 59 years
  • Percentage female: 28%

Inclusion criteria:

  • Patients between 18 and 74 years of age with diabetes mellitus on low-dose aspirin therapy with angiographically documented coronary artery disease

Exclusion criteria:

  • History of stroke, transient ischemic attack, or intracranial bleeding
  • Allergy to prasugrel or ticagrelor
  • Treatment with a P2Y12 receptor antagonist or an oral anticoagulant in the prior 30 days
  • Clinical indication for treatment with a P2Y12 receptor antagonist (i.e., acute coronary syndrome or coronary stenting procedure in the past 12 months)
  • Weight <60 kg
  • Blood dyscrasia, bleeding diathesis, or active bleeding
  • Thrombocytopenia or anemia
  • Hemodynamic instability
  • Creatinine clearance <30 ml/min or hepatic dysfunction
  • Sick sinus syndrome or high degree atrioventricular block without a pacemaker
  • Treatment with drugs interfering with cytochrome P450 3A4 metabolism
  • Pregnant or lactating women

Principal Findings:

Prasugrel versus ticagrelor pharmacodynamic profiles were compared at various time points for the following tests:

  • VerifyNow: At 30 minutes (p = 0.22), at 2 hours (p = 0.086), and at 1 week (p = 0.022)
  • Vasodilator-stimulated phosphoprotein (VASP): At 30 minutes (p = 0.19), at 2 hours (p = 0.80), and at 1 week (p = 0.98)
  • Light transmittance aggregometry (LTA) 20 µM adenosine diphosphate (ADP): At 30 minutes (p = 0.97), at 2 hours (p = 0.78), and at 1 week (p = 0.65)
  • Multiple electrode aggregometry (MEA) ADP: At 30 minutes (p = 0.67), at 2 hours (p = 0.76), and at 1 week (p = 0.39)


Among patients with diabetes mellitus and coronary artery disease, the pharmacodynamic profiles of prasugrel versus ticagrelor were largely similar. The only comparison which favored ticagrelor was with the VerifyNow assay at 1 week. Among patients with an indication for a potent ADP receptor antagonist (i.e., percutaneous coronary intervention during an acute coronary syndrome), the use of either prasugrel or ticagrelor is acceptable.


Franchi F, Rollini F, Aggarwal N, et al. A pharmacodynamic comparison of prasugrel versus ticagrelor in patients with type 2 diabetes mellitus and coronary artery disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 study. Circulation 2016;134:780-92.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Interventions and ACS, Interventions and Coronary Artery Disease

Keywords: Acute Coronary Syndrome, Adenosine Diphosphate, Aspirin, Cell Adhesion Molecules, Coronary Artery Disease, Diabetes Mellitus, Type 2, Microfilament Proteins, Percutaneous Coronary Intervention, Pharmacology, Platelet Aggregation Inhibitors, Purinergic P2Y Receptor Antagonists

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