Pharmacodynamic Effect of Prasugrel vs. Ticagrelor in Diabetes
Condition: Diabetes Mellitus; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Diabetes Mellitus
Study type: Interventional

Summary: 
      Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic
      events. This may be in part attributed to the fact that these patients have reduced response
      to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel,
      used for secondary prevention of ischemic events. Prasugrel and ticagrelor are recently
      approved P2Y12 receptor inhibitors which, compared with clopidogrel, have more potent
      antiplatelet effects. Head-to-head comparisons between the two drugs are lacking.
    

Detailed description: 
      Patients with diabetes mellitus (DM) have an increased risk of adverse atherothrombotic
      events. This may be in part attributed to the fact that these patients have reduced response
      to oral antiplatelet medications, in particular the P2Y12 receptor inhibitor clopidogrel,
      used for secondary prevention of ischemic events. Upregulation of platelet P2Y12 receptor
      mediated signaling has been shown in DM patients and may contribute to these pharmacodynamic
      observations, suggesting the need for more potent P2Y12 inhibiting strategies in these
      patients. Prasugrel and ticagrelor are recently approved P2Y12 receptor inhibitors which,
      compared with clopidogrel, have more potent antiplatelet effects. Therefore, prasugrel and
      ticagrelor represent attractive treatment options for patients with DM. This is also
      supported by the DM sub-group analysis of the pivotal TRITON-TIMI 38 (Trial to Assess
      Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with
      Prasugrel-Thrombolysis in Myocardial Infarction) and PLATO (Platelet Inhibition and Patient
      Outcomes) trials, which have led to approval of prasugrel and ticagrelor, respectively.
      Although results of these sub-group analysis suggest that prasugrel is associated with an
      enhanced benefit in DM patients, while ticagrelor effects in DM patients are consistent with
      the overall study population, only head-to-head comparisons between the two drugs can
      elucidate if these exert differential effects on platelets from DM patients. However, the
      pharmacodynamic studies comparing prasugrel with ticagrelor in DM patients are lacking. The
      ever growing DM population at high risk of recurrent atherothrombotic events underscores the
      need to define antiplatelet treatment strategies leading to more optimal platelet inhibition
      in these patients.
    

Intervention name(s): Prasugrel; Ticagrelor
Intervention type(s): Drug; Drug
Intervention description(s): Patients receiving prasugrel will be treated with 60mg loading dose and 10mg maintenance dose; Patients receiving ticagrelor will be treated with a 180mg loading dose and 90mg bid maintenance dose
Other intervention name(s): Effient; Brillinta
Intervention MeSH terms: Ticagrelor; Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Diabetes mellitus; Coronary artery disease; prasugrel; ticagrelor