A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function:
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Intervention: Prasugrel; Ticagrelor
Intervention description: Comparison of platelet reactivity between prasugrel and ticagrelor; Comparison of platelet reactivity between prasugrel and ticagrelor
Intervention MeSH terms: Ticagrelor; Prasugrel Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: Coronary Artery Disease; Percutaneous Coronary Intervention; Genetic Polymorphism; Pharmacodynamic

Summary:

      Numerous studies have shown that pharmacodynamics (PD) response profiles vary among
      clopidogrel treated patients and that individuals with reduced response have an increased
      risk of recurrent ischemic events. There are multiple factors contributing to clopidogrel
      response variability, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme.
      In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of
      clopidogrel pro-drug into its active metabolite. Thus, patients carrying LOF alleles have
      lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition,
      which translates into an increased rate of adverse cardiovascular events, particularly in the
      setting of percutaneous coronary intervention (PCI). Prasugrel and ticagrelor are novel
      generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic
      event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms.
      However, to date there are limited head-to-head PD comparisons between these two new P2Y12
      receptors blockers, and there are no studies assessing on how these agents behave among
      CYP2C19 LOF carriers. The aim of the present study is to compare the PD effects of prasugrel
      versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel
      point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid
      identification of CYP2C19 genetic status.
    

Eligibility criteria:

        -  Inclusion criteria:

               1. Patients scheduled for left heart catheterization and undergoing PCI

               2. Age 18-75 years

               3. On aspirin (81mg) or aspirin (81mg) and clopidogrel (75mg/day)

               4. Presence of at least one 2C19 LOF allele

          -  Exclusion criteria:

               1. Known allergies to aspirin, prasugrel, ticagrelor, or clopidogrel

               2. Age >75 years

               3. Weight <60kg

               4. Considered at high risk for bleeding

               5. History of ischemic or hemorrhagic stroke or transient ischemic attack

               6. Known severe hepatic dysfunction

               7. On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran,
                  apixaban, rivaroxaban)

               8. Use of glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)

               9. Blood dyscrasia or bleeding diathesis

              10. Platelet count <80x106/mL

              11. Hemoglobin <10 g/dL.

              12. Active bleeding or hemodynamic instability

              13. Creatinine Clearance <30 mL/minute

              14. Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker
                  protection.

              15. Current treatment with drugs interfering with CYP3A4 metabolism (to avoid
                  interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole,
                  clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir,
                  atazanavir, and telithromizycin.

              16. Pregnant females* *Women of childbearing age must use reliable birth control
                  (i.e. oral contraceptives) while participating in the study.