Atrial Fibrillation, Coronary Artery Disease, Stable Angina, Stable Chronic Angina
Conditions
Keywords
Edoxaban, antiplatelet, anticoagulant
Brief summary
This study evaluates the efficacy and safety of Edoxaban with the combination of edoxaban and antiplatelet in patients with stable CAD (coronary artery stenosis ≥50% on medical treatment or revascularized stable CAD \[≥ 12 months for acute coronary syndrome and ≥ 6 months after stable CAD\]) and high-risk atrial fibrillation (CHA2DS2-VASc score ≥2).
Interventions
Taking edoxaban (Lixiana™, Daiichi-Sankyo Inc.) 60mg once daily. The dose of edoxaban will be reduced to 30mg once daily in patients with estimated creatinine clearance 15≤CrCL≤50mL/min by Cockcroft-Gault equation or weight is ≤60kg.
DRUGEdoxaban plus Single Antiplatelet Agent
Type of antiplatelet agent is dependant upon the investigator's discretion, but aspirin 100mg once daily or clopidogrel 75mg once daily was recommended.
Sponsors
CardioVascular Research Foundation, Korea
Gi-Byoung Nam
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. A subject was ≥ 18 years of age 2. Patients with nonvalvular atrial fibrillation with high embolic risk (CHA2DS2-VASc score ≥2) 3. Patients with Stable coronary artery disease * Anatomically confirmed coronary artery disease (with ≥50% stenosis of major epicardial coronary artery documented by cardiac catheterization or coronary computed tomographic angiography) on medical therapy alone. * Revascularized coronary artery disease (either Percutaneous Coronary Intervention or coronary bypass surgery) whom the last revascularization should be performed ≥12 months before study enrollment for the acute coronary syndrome and ≥6 months for stable angina pectoris.
Exclusion criteria
1. Patients with thrombocytopenia 2. High risk of bleeding which prohibits the anticoagulant use. (baseline comorbidities, hyper or hypercoagulable state, increased prothrombin time or activated partial thromboplastin time) 3. Prior history of intracranial haemorrhage 4. Mechanical prosthetic valve or moderate to severe mitral stenosis 5. The risk of bleeding increased due to the following reasons; * i. history of gastrointestinal ulcers within 1 month * ii. Malignant tumor with high risk of bleeding * iii. Brain or spinal cord injury within 1 month * iv. History of intracranial or intracerebral hemorrhage within 12 months * v. Esophageal varices * vi. Spinal cord vascular abnormalities or intracerebral vascular abnormalities * vii. Active bleeding * viii. Hemoglobin level \<7.0 g/dL or platelet count ≤ 50,000 / mm3 * ix. History of major surgery within 1 month 6. Uncontrolled severe hypertension 7. Hemodynamically Unstable or pulmonary embolism requiring thrombolysis or pulmonary embolectomy 8. History of hypersensitivity to Edoxaban, aspirin, or clopidogrel 9. Genetic problem with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption 10. Planned Percutaneous Coronary Intervention or coronary bypass surgery was planned within 1 year after randomization 11. Liver cirrhosis or liver dysfunction (AST or ALT \> x3 of normal range or coagulation abnormality) 12. Estimated CrCl by Cockcroft-Gault equation\<15 mL/min 13. Life expectancy less than 12 months 14. The subject was unable to provide written informed consent or participate in long-term follow-up 15. Pregnant and/or lactating women 16. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of net Clinical Outcome | 1 year | composites of death, stroke, systemic embolic event, myocardial infarction, unplanned revascularization of a major coronary artery, major bleeding, and clinically relevant non-major bleeding event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of cardiovascular death | 1 year | — |
| Rate of myocardial infarction | 1 year | — |
| Rate of ischemic stroke | 1 year | — |
| Rate of systemic embolism | 1 year | — |
| Rate of unplanned revascularization | 1 year | — |
| Rate of composite of hard outcomes | 1 year | all cause death, myocardial infarction, ischemic stroke, and systemic embolism |
| Rate of all cause death | 1 year | — |
| Rate of composite of Major or clinically relevant non-major bleeding | 1 year | 1. Major bleeding * Fatal bleeding * Bleeding in the critical site (Intracranial, retroperitoneal, intraocular, intraspinal, intra-articular, pericardial, intramuscular with compartment syndrome) * Bleeding causing a fall in haemoglobin level of 2g/dL or leading to transfusion of two or more units of whole blood or red cells. 2. Clinically relevant non-major bleeding defined as any sign or symptom of haemorrhage that does not fit the criteria for The International Society on Thrombosis and Haemostasis (ISTH) major bleeding but requiring medical intervention, leading to hospitalization, or prompting a medical evaluation. Specifically bleeding that meet one of following criteria. * bleeding that resulted in hospitalization * medical or surgical intervention for bleeding * an unscheduled clinic visit, or * a change in physician-directed antithrombotic therapy. |
| Rate of fatal bleeding | 1 year | International Society on Thrombosis and Haemostasis(ISTH), The Bleeding Academic Research Consortium (BARC)5 |
| Rate of major bleeding | 1 year | ISTH, BARC 3, The Thrombolysis in Myocardial Infarction (TIMI) major bleeding |
| Rate of minor bleeding | 1 year | ISTH, BARC and TIMI criteria |
| Rate of intracranial hemorrhage | 1 year | — |
| Rate of gastrointestinal hemorrhage | 1 year | — |
| Rate of stent thrombosis | 1 year | — |
Countries
South Korea
Outcome results
None listed