Vorapaxar as an Add-On Antiplatelet Therapy in Patients With and Without Diabetes Mellitus
Condition: Myocardial Infarction; Diabetes Mellitus; Peripheral Arterial Disease
MeSH terms: Myocardial Infarction; Peripheral Arterial Disease; Peripheral Vascular Diseases; Diabetes Mellitus; Infarction
Intervention: Vorapaxar; Clopidogrel; Aspirin
Intervention description: Triple therapy with DAPT plus vorapaxar (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days; Triple therapy with DAPT plus vorapaxar (vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days; Triple therapy with DAPT plus vorapaxar(vorapaxar 2.5mg od plus clopidogrel 75 mg od and aspirin 81 mg od) will be administered for 30 days; then patients will stop aspirin and will take dual treatment (vorapaxar 2.5mg od plus clopidogrel 75 mg od ) for other 30 days
Intervention MeSH terms: Aspirin; Clopidogrel; Vorapaxar
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myocardial infarction; diabetes mellitus; vorapaxar; peripheral arterial disease

Summary:

      Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor, more frequently
      clopidogrel, represents the standard of care for the long-term secondary prevention of
      atherothrombotic events in patients with myocardial infarction (MI) or peripheral arterial
      disease (PAD). However, rates of ischemic recurrences remain high. Vorapaxar is a
      protease-activated receptor (PAR)-1 inhibitor, which exerts potent inhibition of
      thrombin-mediated platelet aggregation. Patients with diabetes mellitus (DM) are known to be
      at increased risk of recurrent atherothrombotic events, which translates into worse outcomes,
      despite the use of standard of care therapy. This is in part due to the hyperreactive
      platelet phenotype, which characterizes DM patients, and to inadequate response to oral
      antiplatelet agents, including clopidogrel. Therefore, vorapaxar is an attractive treatment
      option for DM patients with a prior MI. The pharmacodynamic (PD) effects of vorapaxar in DM
      patients and how these may differentiate from non-DM patients has not been explored. Further,
      the role of vorapaxar as part of a dual antithrombotic treatment regimen combined with
      clopidogrel (and stopping aspirin) represents another important area of clinical interest.
      The proposed prospective, parallel-design study conducted in patients post-MI or with PAD
      with and without DM will aim the assess the pharmacodynamic effects of vorapaxar in addition
      to standard DAPT with aspirin and clopidogrel as well as in combination with clopidogrel only
      following aspirin withdrawal.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients with a prior MI between 2 weeks and 24 months or with PAD.

          2. On DAPT with low-dose aspirin (81mg od) and clopidogrel (75mg od) as per
             standard-of-care for at least 14 days.

          3. Age ≥ 18 years old.

        Exclusion criteria:

          1. History of acute coronary syndrome in the previous 2 weeks.

          2. History of stroke, transient ischemic attack, or intracranial hemorrhage.

          3. Active pathological bleeding, history of bleeding events or increased risk of
             bleeding.

          4. Known severe hepatic impairment.

          5. Use of strong cytochrome P450 3A4 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).

          6. On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran,
             rivaroxaban, apixaban, edoxaban).

          7. On treatment with any antiplatelet agent other than aspirin and clopidogrel in the
             past 14 days.

          8. Creatinine clearance <30 mL/minute.

          9. Platelet count <80x106/mL

         10. Hemoglobin <10g/dL

         11. Hemodynamic instability

         12. Pregnant females