Vorapaxar in Patients With Prior Myocardial Infarction Treated With Prasugrel and Ticagrelor
Condition: Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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). The novel P2Y12 receptor inhibitors prasugrel and
      ticagrelor are characterized by more prompt, potent, and predictable antiplatelet effects
      compared with clopidogrel and are associated with a greater reduction of ischemic events in
      acute coronary syndrome patients. 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 novel, orally
      active, competitive and slowly reversible 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. A
      large-scale clinical trial showed that the use of vorapaxar (2.5 mg once/daily) in addition
      to standard antiplatelet therapy (including aspirin and a P2Y12 receptor inhibitor) was
      effective in the secondary prevention of recurrent thrombotic events in patients with
      previous atherothrombosis, in particular in patients with prior MI, at the expense of an
      increase in major bleeding. 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 state-of-the-art antiplatelet therapy in the post-MI setting,
      including prasugrel or ticagrelor, is largely unexplored. This may indeed represent a
      limitation for the uptake of vorapaxar in modern day clinical practice where these agents are
      being more broadly utilized. 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. Pharmacodynamic assessments will be performed at multiple time points and
      with different assays exploring multiple pathways of platelet aggregation. Exploratory
      assessments on the safety of such approach will also be evaluated.
    

Intervention name(s): Prasugrel; Vorapaxar; Aspirin; Ticagrelor
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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)
Other intervention name(s): Effient; Zontivity; ASA (acetylsalicylic acid); Brilinta
Intervention MeSH terms: Aspirin; Ticagrelor; Prasugrel Hydrochloride; Vorapaxar
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: prasugrel; ticagrelor; vorapaxar