Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention
Condition: Cardiovascular Disease; Interventional Cardiology
MeSH terms: Cardiovascular Diseases
Intervention: Aspirin; Placebo; ticagrelor
Intervention MeSH terms: Aspirin; Ticagrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 9006.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PCI; DAPT; ticagrelor; aspirin

Summary:

      The purpose of this study is to compare the use of ticagrelor alone versus ticagrelor and
      aspirin together. Both ticagrelor and aspirin stop platelets from sticking together and
      forming a blood clot that could block blood flow to the heart. This study will look to
      determine the effectiveness and safety of ticagrelor alone, compared to ticagrelor plus
      aspirin in reducing clinically relevant bleeding and in reducing ischemic adverse events
      among high-risk patients who have had a percutaneous intervention with at least one
      drug-eluting stent. A patient is considered high-risk if they meet certain clinical and/or
      anatomic criteria.

      Up to 9000 subjects will be enrolled at the time of their index PCI. Subjects meeting
      randomization eligibility criteria at 3 months post enrollment will be randomized to either
      ticagrelor plus aspirin or ticagrelor plus placebo for an additional 12 months. Follow-up
      clinic visits will be performed at 3 months, 9 months and 15 months post enrollment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  High-risk patients who have undergone successful 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

          -  Thrombotic target lesion(s)

          -  Bifurcation lesions with Medina X,1,1 classification requiring at least 2 stents

          -  Left main (≥50%) or proximal LAD (≥70%) lesion

          -  Calcified target lesion(s) 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)

          -  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