Vorapaxar in Patients With Prior Myocardial Infarction Treated With Prasugrel and Ticagrelor
Condition: Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Intervention: Prasugrel; Vorapaxar; Aspirin; Ticagrelor
Intervention description: Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily); Vorapaxar will be administered at the dose of 2.5mg once daily; Aspirin will be administered at the dose of 81mg once daily; Patients will continue treatment with either prasugrel (10mg once daily) or ticagrelor (90mg twice/daily)
Intervention MeSH terms: Aspirin; Ticagrelor; Prasugrel Hydrochloride; Vorapaxar
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 130.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: prasugrel; ticagrelor; vorapaxar

Summary:

      Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the
      standard of care for the long-term secondary prevention of atherothrombotic events in
      patients with myocardial infarction (MI). However, rates of ischemic recurrences remain high,
      which may be in part due to the fact that other platelet signaling pathways, such as
      thrombin-induced platelet aggregation, continue to be activated. Vorapaxar is a
      protease-activated receptor (PAR)-1 inhibitor, which exerts potent inhibition of
      thrombin-mediated platelet aggregation. It is approved for clinical use by the Food and Drug
      Administration for the reduction of thrombotic cardiovascular events in patients with a
      history of MI or with peripheral arterial disease. However, to date clinical trial experience
      with vorapaxar has been almost exclusively with the P2Y12 receptor inhibitor clopidogrel and
      the effects of vorapaxar in combination with antiplatelet therapy including prasugrel or
      ticagrelor, is largely unexplored. Further, the role of vorapaxar as part of a dual
      antithrombotic treatment regimen, in addition to a novel P2Y12 receptor inhibitor, with
      withdrawal of aspirin, represents another important area of clinical interest as it has the
      potential to maximize ischemic protection while reducing the risk of bleeding. The proposed
      prospective, randomized, parallel-design, open label, study conducted in a real world
      clinical setting of post-MI patients will aim to assess the pharmacodynamic effects of
      vorapaxar in addition to antiplatelet therapy with a novel P2Y12 receptor inhibitor
      (prasugrel or ticagrelor) with and without aspirin.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients with a prior MI within the previous 2 weeks to 12 months.

          2. On DAPT with low-dose aspirin (81mg od) and either prasugrel (10mg od) or ticagrelor
             (90mg bid) as per standard-of-care for at least 2 weeks.

          3. Free from bleeding and ischemic events after the index MI event.

          4. Age between 18 and 75 years old.

        Exclusion criteria:

          1. History of stroke, transient ischemic attack, or intracranial hemorrhage.

          2. Active pathological bleeding, history of bleeding events or increased risk of
             bleeding.

          3. Known severe hepatic impairment.

          4. Age >75 years.

          5. Body weight <60 Kg.

          6. Use of strong Cytochrome P450 3A inhibitors (e.g., ketoconazole, itraconazole,
             posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir,
             indinavir, boceprevir, telaprevir, telithromycin and conivaptan) or inducers (e.g.,
             rifampin, carbamazepine, St. John's Wort and phenytoin).

          7. On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran,
             rivaroxaban, apixaban, edoxaban).

          8. On treatment with any antiplatelet agent other than aspirin, prasugrel and ticagrelor
             in the past 14 days.

          9. Creatinine clearance <30 mL/minute.

         10. Platelet count <80x106/mL

         11. Hemoglobin <10g/dL

         12. Hemodynamic instability

         13. Pregnant females