Angina Pectoris, Bleeding, Coronary Artery Bypass Grafting, Coronary Artery Disease, Dual Antiplatelet Therapy, Myocardial Infarction, Myocardial Ischemia
Conditions
Keywords
Coronary Artery Bypass Grafting, Ticagrelor, Aspirin, Dual Antiplatelet Therapy, De-escalated Dual Antiplatelet Therapy, Great Saphenous Vein, Bleeding
Brief summary
Ticagrelor-based De-escalation of Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting trial (TOP-CABG trial) is a multicenter, randomized, double-blind, non-inferiority, parallel controlled trial. The aim of TOP-CABG is to investigate whether de-escalated dual antiplatelet therapy (De-DAPT) is non-inferior to dual antiplatelet therapy (DAPT) in efficacy on inhibiting great saphenous vein (SVG) graft occlusion and is superior in reducing bleeding events in patients accepting coronary artery bypassing grafting.
Detailed description
After informed consent, at least 10 centers and 2,300 eligible admissions will be recruited. Eligible patients would be randomized (1:1) in double-blind manner (patients and treating physicians) to dual antiplatelet therapy (DAPT) group (ticagrelor 90mg bid and aspirin 100 mg qd for 12 month) and de-escalated DAPT (De-DAPT) group (90mg bid and aspirin 100 mg qd for first 3 months, and then aspirin 100 mg qd and placebo for 9 months).
Interventions
DRUGDe-escalated Dual Antiplatelet Therapy
ticagrelor (90mg twice daily) + aspirin (100 mg once daily) during first 3 months post CABG, then switching to aspirin (100 mg once daily) + placebo (twice daily) for 9 months.
DRUGDual Antiplatelet Therapy
Ticagrelor (90mg twice daily) + aspirin (100 mg once daily) for 1 year post CABG.
Sponsors
China National Center for Cardiovascular Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1\. Patients 18-80 of age. 2. Patients undergo planned CABG for the first time with ≥1 SVGs 3. Patients with written informed consent.
Exclusion criteria
1. Concomitant valve (excluding aortic bioprosthesis), aorta, or rhythm surgery during the same session. 2. Patients undergo emergency CABG. 3. Patients with single coronary artery disease. 4. Patients with cardiogenic shock and hemodynamic instability. 5. Patients with sick sinus syndrome, 2nd or 3rd atrioventricular block. 6. Patients with contraindications for coronary computed tomography angiography or coronary angiography (eg. contrast allergy). 7. Use of other antiplatelet drugs than aspirin or ticagrelor (clopidogrel, prasugrel, etc) and unable to discontinue this medication after CABG, in the treating physician's or the investigator's opinion. 8. Patients who take oral anticoagulants before CABG and have to use anticoagulants after surgery. 9. Contraindication for the use of ticagrelor or aspirin (ie. history of bleeding diathesis within 3 months prior presentation, severe gastrointestinal bleeding within 1year prior presentation, peptic ulcer without gastrointestinal bleeding in past 3 years or history of intracranial hemorrhage, allergy, severe gastrointestinal reaction caused by aspirin). 10. Placement of a drug-eluting stent in a coronary or cerebral artery within 6 months of CABG or placement of a bare-metal stent in a coronary or cerebral artery within 1 month of CABG 11. Thrombocytopenia before CABG (\< 100 x 109/L). 12. patients with severe renal function impairment requiring dialysis or active liver disease, including patients with unexplained persistent elevated transaminase or any transaminase more than 3 times the normal limit. 13. Use of strong inhibitors of CYP3A4 14. Patients who have to use methotrexate and ibuprofen. 15. Patients with active malignant tumors with increase in bleeding risk in the investigator's opinion 16. Pregnant patients, patients who have given birth within the past 90 days, or who are breastfeeding. 17. Premenopausal women who do not take adequate contraception. Adequate contraception refers to the adoption of at least two reliable methods of contraception, one of which must be a barrier method of contraception. 18. CABG volume of the surgeon less than 50.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 100% great saphenous vein (SVG) grafts occlusions | During 0-day to 1-year after CABG | 100% SVG During 0-day to 1-year after CABG (Fitz Gibbon grade O). SVG grafts were assessed by multislice computed tomographic angiography or coronary angiography and interpreted by an independent Image Data Review Centre blinded to treatment allocation |
| Bleeding events | During 0-day to 1-year after CABG | Bleeding events as defined by the BARC classification ≥ 2 at 1 year after CABG. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SVG Failure | During 0-day to 1-year after CABG | a composite of SVG occlusion in any SVG as defined above, SVG revascularization, myocardial infarction in myocardial territory supplied by an SVG, or sudden death, as defined by the American College of Cardiology and American Heart Association and judged by an independent Clinical Endpoint Committee blinded to treatment allocation |
| Graft stenosis and occlusion | During 0-day to 1-year after CABG | Significant (≥70%) venous or arterial graft stenosis and any (venous or arterial) graft occlusion |
| MACCE episodes | Within 1-year after CABG | MACCE episodes within 1-year after CABG (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or revascularization), as defined by the American College of Cardiology and American Heart Association and judged by an independent Clinical Endpoint Committee blinded to treatment allocation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subgroup analysis 16 for primary outcome | 1 year | Grafts (\<3 , ≥3) |
| Subgroup analysis 1 for primary outcome | 1 year | Age (\<65 years, ≥65 years) |
| Subgroup analysis 2 for primary outcome | 1 year | Sex (male, female) |
| Subgroup analysis 3 for primary outcome | 1 year | Body mass index (\<25 kg/m2, ≥25 kg/m2) |
| Subgroup analysis 4 for primary outcome | 1 year | Acute Coronary Syndrome (yes, no) |
| Subgroup analysis 5 for primary outcome | 1 year | Hypertension (yes, no) |
| Subgroup analysis 11 for primary outcome | 1 year | eGFR (\<60/ml/min/1.75m2, ≥60/ml/min/1.75m2) |
| Subgroup analysis 7 for primary outcome | 1 year | Dyslipidemia (yes, no) |
| Subgroup analysis 8 for primary outcome | 1 year | Prior myocardial infarction (yes, no) |
| Subgroup analysis 9 for primary outcome | 1 year | Current smoker (yes, no) |
| Subgroup analysis 10 for primary outcome | 1 year | Left ventricular ejection fraction (\<50%, ≥50%) |
| Subgroup analysis 17 for primary outcome | 1 year | Syntax score(≤22, 23-32 , ≥33) |
| Subgroup analysis 6 for primary outcome | 1 year | Diabetes (yes, no) |
| Subgroup analysis 12 for primary outcome | 1 year | Statin (yes, no) |
| Subgroup analysis 13 for primary outcome | 1 year | Beta-blocker (yes, no) |
| Subgroup analysis 14 for primary outcome | 1 year | RASi (yes, no) |
| Subgroup analysis 15 for primary outcome | 1 year | Off-pump (yes, no) |
Countries
China
Outcome results
None listed