Tailored Antiplatelet Therapy Following PCI

TAILOR-PCI is a multi-site, open label, prospective, randomized trial testing the hypothesis
that after percutaneous coronary intervention (PCI), using a genotyping strategy ticagrelor
90 mg twice per day is superior to clopidogrel 75 mg per day in reducing a composite endpoint
of major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction,
non-fatal stroke, severe recurrent ischemia, cardiovascular (CV) death, and stent thrombosis
(primary endpoints) in CYP2C19 reduced function allele patients. Patients who undergo PCI
will be randomized to a conventional therapy arm (i.e., to receive clopidogrel 75 mg once
daily without prospective genotyping guidance) versus a prospective CYP2C19 genotype-based
anti-platelet therapy approach (ticagrelor 90 mg bid in CYP2C19 *2 or *3 reduced function
allele patients, clopidogrel 75 mg once daily in non-*2 or -*3 CYP2C19 patients). Buccal
swabs will be obtained for those subjects randomized to the prospective genotyping arm. All
subjects will have a blood sample drawn for DNA analysis but genotyping using these DNA
samples will be performed only after completion of the duration of anti-platelet therapy
(i.e., after one year). The primary endpoints will be assessed prospectively and will be
compared between the conventional arm and the prospective genotyping arm among those
identified as reduced function CYP2C19 allele carriers according to the 1-year genotype
results.

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.)