Tailored Antiplatelet Therapy Following PCI
Condition: Coronary Artery Disease; Acute Coronary Syndrome; Stenosis
MeSH terms: Coronary Artery Disease; Acute Coronary Syndrome
Intervention: Clopidogrel; Ticagrelor
Intervention description: One 75 mg tablet per day by mouth for one year; One 90 mg tablet twice per day by mouth for one year
Intervention MeSH terms: Clopidogrel; Ticagrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5276.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: percutaneous coronary intervention; angioplasty

Summary:

      Clopidogrel is an anti-platelet medication approved by the U.S. Federal Drug Administration
      (FDA) for use in patients who undergo Percutaneous Coronary Intervention (PCI) with coronary
      stent implantation. Anti-platelet medications work to prevent blood clots from forming. Some
      studies have suggested that patients who have a certain genetic liver enzyme abnormality
      (known as cytochrome P450 2C19 [CYP2C19] *2 or *3 allele) may have a reduced ability to
      activate clopidogrel, and therefore may have a lowered response to clopidogrel. It is thought
      that perhaps people who have a coronary stent procedure may have this genetic liver enzyme
      abnormality. There is a research genetic test available to determine whether or not someone
      has this genetic liver enzyme abnormality. Ticagrelor, is a newer anti-platelet drug that is
      not dependent on the CYP2C19 liver enzyme for its activation and hence in poor clopidogrel
      metabolizers, alternative drugs like Ticagrelor have been recommended for use as an
      anti-platelet agent after PCI. The purpose of this study is to determine if genetic testing
      can identify the best anti-platelet therapy, for patients who undergo a coronary stent
      placement and do not activate clopidogrel very well.
    

Eligibility criteria:

        Inclusion

          -  Patient >18 years of age

          -  Patient presents with acute coronary syndrome (ACS) or stable coronary artery disease
             (CAD)

          -  Patient is eligible for PCI

          -  Patient is willing and able to provide informed written consent

        5.3 Exclusion

          -  Patient not able to receive 12 months of dual anti-platelet therapy

          -  Failure of index PCI

          -  Patient or physician refusal to enroll in the study

          -  Patient with known CYP2C19 genotype prior to randomization

          -  Planned revascularization of any vessel within 30 days post-index procedure and/or of
             the target vessel(s) within 12 months post-procedure

          -  Anticipated discontinuation of clopidogrel or ticagrelor within the 12 month follow up
             period, example for elective surgery

          -  Serum creatinine >2.5 mg/dL within 7 days of index procedure

          -  Platelet count <80,000 or >700,000 cells/mm3, or white blood cell count <3,000
             cells/mm3 if persistent (at least 2 abnormal values) within 7 days prior to index
             procedure.

          -  History of intracranial hemorrhage

          -  Known hypersensitivity to clopidogrel or ticagrelor or any of its components

          -  Patient is participating in an investigational drug or device clinical trial that has
             not reached its primary endpoint

          -  Patient previously enrolled in this study

          -  Patient is pregnant, lactating, or planning to become pregnant within 12 months

          -  Patient has received an organ transplant or is on a waiting list for an organ
             transplant

          -  Patient is receiving or scheduled to receive chemotherapy within 30 days before or
             after the procedure

          -  Patient is receiving immunosuppressive therapy or has known immunosuppressive or
             autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematous,
             etc.)

          -  Patient is receiving chronic oral anticoagulation therapy (i.e., vitamin K antagonist,
             direct thrombin inhibitor, Factor Xa inhibitor)

          -  Concomitant use of simvastatin/lovastatin > 40 mg qd

          -  Concomitant use of potent CYP3A4 inhibitors (atazanavir, clarithromycin, indinavir,
             itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir,
             telithromycin and voriconazole) or inducers (carbamazepine, dexamethasone,
             phenobarbital, phenytoin, rifampin, and rifapentine)

          -  Non-cardiac condition limiting life expectancy to less than one year, per physician
             judgment (e.g. cancer)

          -  Known history of severe hepatic impairment

          -  Patient has a history of bleeding diathesis or coagulopathy or will refuse blood
             transfusions

          -  Patient has an active pathological bleeding, such as active gastrointestinal (GI)
             bleeding

          -  Inability to take aspirin at a dosage of 100 mg or less

          -  Current substance abuse (e.g., alcohol, cocaine, heroin, etc.)