Left Atrial Appendage CLOSURE in Patients With Atrial Fibrillation at High Risk of Stroke and Bleeding Compared to Medical Therapy: a Prospective Randomized Clinical Trial
Overview
- Phase
- Phase 4
- Intervention
- CE-mark approved LAA closure devices
- Conditions
- Atrial Fibrillation
- Sponsor
- Charite University, Berlin, Germany
- Enrollment
- 912
- Locations
- 42
- Primary Endpoint
- Primary endpoint (net clinical benefit)
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
The study goal is to determine the clinical benefit of percutaneous catheter-based left atrial appendage (LAA) closure in patients with non-valvular atrial fibrillation (NVAF) at high risk of stroke (CHA2DS2-VASc Score ≥2) as well as high risk of bleeding as compared to best medical care (including a [non-vitamin K] oral anticoagulant [(N)OAC] when eligible).
Detailed Description
The individualized therapy with oral anticoagulants is considered to be an essential preventive therapy in patients with atrial fibrillation. The risk of stroke can be reduced by approximately 65%. However, long-term anticoagulation therapy also increases the risk of major bleeding. A significant proportion of patients at high risk of stroke do not tolerate long-term anticoagulation due to various relative or absolute contraindications. As demonstrated in previous studies with non-vitamin K antagonist anticoagulants (NOAK), 20-25% of patients were unable to tolerate long-term anticoagulation therapy. For this reason, additional therapeutic approaches for stroke prevention in patients with atrial fibrillation have been developed. A promising approach is catheter-based closure of the left atrial appendage, because more than 90% of cardiac thrombi in patients with non-valvular atrial fibrillation are detected in the left atrial appendage. Recent registry studies show that the safety of LAA occluder implantation is promising. However, further scientific studies are required, in order to explore more benefits of the underlying method and eligible patients for implantation. Study objectives: The study goal is to determine the clinical benefit of percutaneous catheter-based left atrial appendage (LAA) closure in patients with non-valvular atrial fibrillation (NVAF) at high risk of stroke (CHA2DS2-VASc Score ≥2) as well as high risk of bleeding as compared to best medical care (including a \[non-vitamin K\] oral anticoagulant \[(N)OAC\] when eligible).
Investigators
Ulf Landmesser
Prof. Dr.
Charite University, Berlin, Germany
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent
- •Documented atrial fibrillation (paroxysmal, persistent, long-standing persistent or permanent)
- •CHA2DS2VASc-Score ≥2
- •High risk of bleeding under oral anticoagulation or contraindication for (N)OAC therapy, in particular patients with at least one of the following conditions:
- •HAS-BLED-Score ≥3
- •Prior intracranial/intraspinal bleed, intraocular bleed compromising vision (BARC: type 3c)
- •Hemorrhagic/bleeding complication fulfilling BARC type 3a or 3b: gastrointestinal tract, genitourinary tract or respiratory tract bleeding, where the patient is considered to be at a persistently increased risk of bleeding, e.g. the cause of bleeding cannot be successfully eliminated
- •Chronic kidney disease with eGFR 15-29 ml/min/1.73 m2
- •Any recurrent bleeding making chronic anticoagulation not feasible
- •Subject eligible for an LAA occluder device
Exclusion Criteria
- •Absolute contraindication to acetylsalicylic acid
- •Comorbidities other than AF requiring chronic (N)OAC therapy, e.g. mechanical heart valve prosthesis
- •Symptomatic carotid disease (if not treated)
- •Complex aortic atheroma with mobile plaque (Kronzon classification grade V)
- •Heart transplant
- •Active infection or symptoms suggestive of COVID-19 infection or active endocarditis or other infections resulting in bacteremia
- •Cardiac tumor
- •Severe liver failure (Child-Pugh class C or liver failure with coagulopathy)
- •Severe renal failure (GFR \<15 ml/min/1.73m2 or current requirement for dialysis defined as current, regular renal replacement therapy performed at least weekly including hemodialysis and peritoneal dialysis within the last 30 days)
- •Pregnancy or breastfeeding
Arms & Interventions
LAA closure group
Left atrial appendage closure by use of CE-mark approved LAA closure devices followed by post procedure treatment (antiplatelet therapy e.g. acetylsalicylic acid, clopidogrel)
Intervention: CE-mark approved LAA closure devices
LAA closure group
Left atrial appendage closure by use of CE-mark approved LAA closure devices followed by post procedure treatment (antiplatelet therapy e.g. acetylsalicylic acid, clopidogrel)
Intervention: Acetylsalicylic acid
LAA closure group
Left atrial appendage closure by use of CE-mark approved LAA closure devices followed by post procedure treatment (antiplatelet therapy e.g. acetylsalicylic acid, clopidogrel)
Intervention: Clopidogrel
Best medical care group
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Intervention: Dabigatran
Best medical care group
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Intervention: Rivaroxaban
Best medical care group
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Intervention: Apixaban
Best medical care group
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Intervention: Edoxaban
Best medical care group
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Intervention: Phenprocoumon
Best medical care group
No left atrial appendage closure. Treatment with best medical care (NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) or VKA (phenprocoumon, warfarin)
Intervention: Warfarin
Outcomes
Primary Outcomes
Primary endpoint (net clinical benefit)
Time Frame: After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.
Survival time free of the composite of: * Stroke (including ischemic or hemorrhagic stroke) * Systemic embolism * Major bleeding (BARC type 3-5) * Cardiovascular or unexplained death
Secondary Outcomes
- Myocardial infarction(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Primary endpoint events per year(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Combined endpoint: MACCE(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Mortality(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Major bleeding(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Systemic embolism(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Ischemic stroke(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Hemorrhagic stroke(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Transient ischemic attack(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Hospitalization for bleeding or cardiovascular event(After 3, 6, and 12 months. Twice a year until 24 months and once a year after 24 months.)
- Changes in cognitive function(At day 0 and after 24 months.)
- Changes in health-related quality of life(At day 0 and after 6, and 12 months, twice a year until 24 months and once a year after 24 months of follow-up.)
- Changes in modified Ranking Scale (mRS)(At day 0, 1 day after implantation (device group only) and after 3, 12 and 24 months.)