Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional

Summary: 
      Dual antiplatelet therapy consisting of aspirin and clopidogrel is the cornerstone of
      treatment for prevention of atherothrombotic events in patients with coronary artery disease
      (CAD) undergoing percutaneous coronary interventions (PCI). Many patients on dual
      antiplatelet therapy in this setting may be affected by other thromboembolic conditions, in
      particular atrial fibrillation, therefore having an indication to also receive oral
      anticoagulation for stroke prevention. Thus, a considerable percentage of patients are under
      "triple therapy" which consists of aspirin plus clopidogrel plus an oral anticoagulant. The
      ever raising population with CAD warranting triple therapy and the growing number of patients
      being treated with dabigatran underscores the importance of understanding the pharmacodynamic
      effects of this treatment regimen.
    

Detailed description: 
      Dual antiplatelet therapy consisting of aspirin and clopidogrel is the cornerstone of
      treatment for prevention of atherothrombotic events in patients with coronary artery disease
      (CAD) undergoing percutaneous coronary interventions (PCI). Many patients on dual
      antiplatelet therapy in this setting may be affected by other thromboembolic conditions, in
      particular atrial fibrillation, therefore having an indication to also receive oral
      anticoagulation for stroke prevention. Thus, a considerable percentage of patients are under
      "triple therapy" which consists of aspirin plus clopidogrel plus an oral anticoagulant.
      Although this combination therapy allows a reduction of atherothrombotic and thromboembolic
      events, patients on triple therapy are at an increased risk of bleeding complications.

      Dabigatran, a synthetic, reversible direct thrombin inhibitor, has been studied as an
      alternative to warfarin in patients with atrial fibrillation and has been shown to be at
      least as efficacious with a favorable safety profile. In particular, dabigatran at a dose of
      110 mg is associated with rates of stroke and systemic embolism similar to warfarin, with
      lower rates of major hemorrhage, while a dose of 150 mg is associated with lower thrombotic
      events with similar rates of bleeding events. These findings have led the Food and Drug
      Administration (FDA) to approve dabigatran for use in atrial fibrillation patients in
      December 2011 and this has also been implemented in practice guidelines to be a superior
      strategy to warfarin. However, the FDA only approved the 150mg formulation.

      Dabigatran has high affinity and specificity for its target serine protease thrombin, and one
      small study shows that dabigatran produced potent inhibition of thrombin-induced platelet
      aggregation in vitro. However, there are no studies assessing the ex vivo pharmacodynamic
      effects of dabigatran in patients on dual antiplatelet therapy. The ever raising population
      with CAD warranting triple therapy and the growing number of patients being treated with
      dabigatran underscores the importance of understanding the pharmacodynamic effects of this
      treatment regimen.
    

Intervention name(s): Dabigatran; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Dabigatran 150mg; Matching placebo tablets
Other intervention name(s): Pradaxa
Intervention MeSH terms: Dabigatran
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Coronary artery disease; antiplatelet therapy; anticoagulant therapy