Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease

Study Overview
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Brief Summary
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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).

Official Title
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A Multi-centre, Open-labelled, Randomized Controlled Trial Comparing Two Different Anticoagulation Strategies in High-risk Atrial Fibrillation and Stable Coronary Artery Disease

Conditions
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Atrial Fibrillation, Coronary Artery Disease, Stable Angina, Stable Chronic Angina

Intervention / Treatment
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* Drug: Edoxaban
* Drug: Single Antiplatelet Agents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria A subject was ≥ 19 years of age Patients with nonvalvular atrial fibrillation with high embolic risk (CHA2DS2-VASc score ≥2) Patients with Stable coronary artery disease Coronary artery angiography or Coronary Computed Tomography Angiography confirmed coronary artery disease (≥50 % stenosis of a major coronary artery) on medical treatment. In case there is clinically significant moderate or more stenosis however the percentage of stenosis on CAG or CCTA is not shown, it will be at the investigator's discretion. 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 Patients with thrombocytopenia High risk of bleeding which prohibits the anticoagulant use. (baseline comorbidities, hyper or hypercoagulable state, increased prothrombin time or activated partial thromboplastin time) Prior history of intracranial haemorrhage or haemorrhage on Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) imaging test Mechanical prosthetic valve or moderate to severe mitral stenosis 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. Arteriovenous malformation vii. Vascular aneurysms viii. Spinal cord vascular abnormalities or intracerebral vascular abnormalities ix. Active bleeding x. Hemoglobin level <7.0 g/dL or platelet count ≤ 50,000 / mm3 xi. History of major surgery within 1 month Uncontrolled severe hypertension Hemodynamically Unstable or pulmonary embolism requiring thrombolysis or pulmonary embolectomy History of hypersensitivity to Edoxaban or clopidogrel Genetic problem with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Planned Percutaneous Coronary Intervention or coronary bypass surgery was planned within 1 year after randomization Liver cirrhosis or liver dysfunction (AST or ALT > x3 of normal range or coagulation abnormality) Estimated CrCl by Cockcroft-Gault equation<15 mL/min Life expectancy less than 12 months The subject was unable to provide written informed consent or participate in long-term follow-up Pregnant and/or lactating women Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edoxaban alone<br> | Drug: Edoxaban<br>* 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.<br>* Other names: Lixiana™;|
| Active Comparator: Combination of edoxaban plus single antiplatelet<br> | Drug: Edoxaban<br>* 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.<br>* Other names: Lixiana™;Drug: Single Antiplatelet Agents<br>* Type of antiplatelet agent is dependant upon the investigator's discretion, but aspirin 100mg once daily is recommended.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of net Clinical Outcome | 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 | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of all cause death |  | 1 year | 
| 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 | all cause death, myocardial infarction, ischemic stroke, and systemic embolism | 1 year | 
| Rate of stent thrombosis |  | 1 year | 
| Rate of composite of Major or clinically relevant non-major bleeding | 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. Clinically relevant non-major bleeding Requires or prolongs hospitalization Requires lab evaluation Requires imaging studies Requires nasal packing or compression Requires a therapeutic procedure Requires interruption of study medication Requires a change in concomitant therapy | 1 year | 
| Rate of fatal bleeding | International Society on Thrombosis and Haemostasis(ISTH), The Bleeding Academic Research Consortium (BARC)5 | 1 year | 
| Rate of major bleeding | ISTH, BARC 3, The Thrombolysis in Myocardial Infarction (TIMI) major bleeding | 1 year | 
| Rate of minor bleeding | ISTH, BARC and TIMI criteria | 1 year | 
| Rate of intracranial hemorrhage |  | 1 year | 
| Rate of gastrointestinal hemorrhage |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Edoxaban, antiplatelet, anticoagulant