Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention

This is a multicenter, prospective, blinded dual-arm study. Up to 9000 high-risk patients who
have undergone successful elective or urgent PCI with at least one locally approved drug
eluting stent discharged on DAPT with aspirin and ticagrelor of at least 3 months intended
duration from centers still to be determined in the U.S., Canada, Europe and Asia. The
primary objective of this study is to determine the impact of antiplatelet monotherapy with
ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing
clinically relevant bleeding (efficacy) among high-risk patients undergoing PCI who have
completed a 3-month course of aspirin plus ticagrelor.

The secondary objective of this study is to determine the impact of antiplatelet monotherapy
with ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing
major ischemic adverse events (safety) among high-risk patients undergoing PCI who have
completed a 3-month course of aspirin plus ticagrelor.

Exploratory objectives include assessing the comparative safety and efficacy of the different
DAPT regimens for individual components of the primary efficacy and secondary safety
objectives.

Inclusion Criteria:

- High-risk patients who have undergone successful elective or urgent PCI with at least
one locally approved drug eluting stent discharged on DAPT with aspirin and ticagrelor
of at least 3 months intended duration will be eligible for the TWILIGHT study.

- Enrollment into the study will require meeting at least one clinical inclusion, one
angiographic inclusion and none of the exclusion criteria.

Clinical Inclusion Criteria:

- Adult patients ≥ 65 years of age

- Female gender

- Troponin Positive acute coronary syndrome

- Established vascular disease defined as previous MI, documented PAD or CAD/PAD
revascularization

- Diabetes mellitus treated with medications (oral hypoglycemic, subcutaneous injection
of insulin)

- Chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) < 60
ml/min/1.73m2 or creatinine clearance (CrCl) < 60 ml/min

Angiographic Inclusion Criteria:

- Multivessel coronary artery disease

- Target lesion requiring total stent length >30 mm

- Bifurcation lesions with Medina X,1,1 classification requiring at least 2 stents

- Left main (≥50%) or proximal LAD (≥70%) lesion

- Calcified target lesion requiring atherectomy

Exclusion Criteria:

- Under 18 years of age

- Contraindication to aspirin

- Contraindication to ticagrelor

- Planned surgery within 90 days

- Planned coronary revascularization (surgical or percutaneous) within 90 days

- Need for chronic oral anticoagulation

- Prior stroke

- Dialysis-dependent renal failure

- Active bleeding or extreme-risk for major bleeding (e.g. active peptic ulcer disease,
gastrointestinal pathology with a raised risk for bleeding, malignancies with a raised
risk for bleeding)

- Emergent or salvage PCI or STEMI presentation.

- Liver cirrhosis

- Life expectancy < 1 year

- Unable or unwilling to provide informed consent

- Women of child bearing potential. Defined: a woman is considered potential (WOBCP)
following menarche and until becoming post-menopausal unless permanently sterile.
Permanent sterilization methods include hysterectomy, bilateral salpingectomy and
bilateral oophorectomy. a postmenopausal state is defined as no menses for 12 months
without an alternative medical cause.

- Fibrinolytic therapy within 24 hours of index PCI

- Concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer

- Platelet count < 100,000 mm3

- Requiring ongoing treatment with aspirin > 325 mg daily