STroke Secondary Prevention With Catheter ABLation and EDoxaban for Patients With Non-valvular Atrial Fibrillation: STABLED Study

Study Overview
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Brief Summary
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Catheter ablation (CA) has been reported to reduce risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) in retrospective studies, but risk and benefit of CA has not been well elucidated in NVAF with recent cerebral infarction in prospective randomized trials.

Detailed Description
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In patients with NVAF, stroke is an independent risk factor for a subsequent cerebral infarction. Although anticoagulant therapy can effectively reduce thromboembolic events, the reported annual recurrence rate in NVAF and previous stroke patients in the real-world is not low even with appropriate antithrombotic treatment; 8.6% in patients with guideline adherent antithrombotic therapy and around 5% in patients treated with anticoagulant therapy. NVAF and recent stroke is high-risk population for stroke recurrence even with anticoagulant therapy, and developing optimal secondary prevention strategy is an urgent task. Catheter ablation (CA) is now widely used to treat symptoms related to NVAF. Some retrospective studies showed a beneficial effect of CA for stroke prevention using age-/sex-matching or propensity-score matching. Moreover, CA have a potential to improve survival or prevent heart failure development in patients with AF. However, the effect of CA for secondary stroke prevention or impact of CA for NVAF patients with recent ischemic stroke for survival or developing heart failure has not been evaluated in a prospective randomized trial. Therefore, in the present study, we intend to compare two groups of patients with NVAF with a history of cerebral infarction: a group receiving standard medical therapy (control group) and a group receiving standard medical therapy plus CA (CA group).

Official Title
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STroke Secondary Prevention With Catheter ABLation and EDoxaban for Patients With Non-valvular Atrial Fibrillation: STABLED Study

Conditions
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Ischemic Stroke, Atrial Fibrillation Non-Rheumatic

Intervention / Treatment
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* Procedure: Catheter ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥20 or ≤85 years at time of giving informed consent Nonvalvular atrial fibrillation History of stroke in previous 6 months Current or planned treatment with edoxaban Modified Rankin scale ≤3 Exclusion Criteria: Symptomatic paroxysmal AF resistant to anti-arrhythmic drugs Presence of left atrial thrombus and left atrial appendage on transthoracic echocardiography, computed tomography or magnetic resonance imaging Unable to take anticoagulation therapy for any reason, including tendency to bleed or considered at high risk for bleeding from anticoagulation therapy. Presence of severe renal disorder (estimated creatinine clearance <30 mL/min by Cockroft-Gault equation) Previous CA or surgical intervention for AF History of treatment with a left atrial appendage closure device Left atrial diameter ≥55 mm on transthoracic echocardiography Ejection fraction ≤35% on transthoracic echocardiography Persistent AF for ≥10 years Pregnant or possibility of pregnancy Unlikely to complete the study, such as due to progressive malignant tumor Participating or planning to participate in another clinical trial Unwilling to participates Judged as incompatible for the study by the investigators

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The included patients were randomly allocated to two groups: (1) Standard medical treatment group and (2) Catheter ablation additional group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard medical therapy group<br>The preferred anticoagulant is edoxaban. Antiarrhythmic drugs are administered as needed for the patient by well-trained cardiologists. | |
| Active Comparator: Catheter ablation group<br>Catheter ablation (CA) should be performed within 1-6 months from the onset of cerebral infarction. CA is based on pulmonary vein isolation, with atrial ablation as required. For conducting CA by a trained and experienced cardiologist, only institutions in which performed >100 CA annually were participated in the present study in principle. | Procedure: Catheter ablation<br>* CA should be performed within 1-6 months from the onset of cerebral infarction. CA is based on pulmonary vein isolation, with atrial ablation as required.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of recurrence of cerebral infarction, systemic embolism, all-cause death, hospitalization for heart failure. | Composite of recurrence of cerebral infarction, systemic embolism, all-cause death, hospitalization for heart failure. | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of cerebral infarction | Recurrence of cerebral infarction | Up to 6 years | 
| Systemic embolism | Symptomatic systemic embolism to other regions than brain, e.g. peripheral or visceral arteries | Up to 6 years | 
| All-cause death | All-cause death | Up to 6 years | 
| Cardiovascular death | Cardiovascular death | Up to 6 years | 
| Hospitalization for heart failure | Hospitalization for heart failure | Up to 6 years | 
| Any bleeding | Any bleeding | Up to 6 years | 
| Intracranial hemorrhage | Intracranial hemorrhage | Up to 6 years | 
| Composite events | all-cause death, onset of stroke, systemic embolism, hospitalization for heart failure, and serious adverse event caused by CA | Up to 6 years | 
| The rate of and related factors to discontinuation of Edoxaban | The rate of and related factors to discontinuation of Edoxaban | Up to 6 years | 
| Recurrence of cerebral infarction in patients with or without discontinuation of Edoxaban | Recurrence of cerebral infarction in patients with or without discontinuation of Edoxaban | Up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulation treatment, catheter ablation