Anticoagulants / Administration & Dosage, Atrial Fibrillation, Hemorrhage, Left Atrial Appendage Closure, Reduced-dose Apixaban, Stroke Prevention in Patients With Atrial Fibrillation, Thromboembolism
Conditions
Keywords
atrial fibrillation, left atrial appendage closure, anticoagulants, reduced dose apixaban
Brief summary
This is a prospective, non-randomized, observational cohort study conducted at the FSBI "NMRC TPM" of the Ministry of Healthcare of the Russian Federation. Left atrial appendage closure (LAAC) has been shown to be non-inferior to oral anticoagulation for preventing cardioembolic events in patients with atrial fibrillation. However, the optimal post-procedural antithrombotic regimen following LAAC remains unclear, with no consensus on evidence-based therapy. Given current trends in cardiology favoring reduced-intensity antithrombotic strategies, this study aims to contribute to the evidence base by evaluating whether LAAC followed by reduced-dose apixaban (2.5 mg BID) for 3 months with subsequent complete withdrawal of antithrombotic therapy is superior to long-term standard-dose DOAC therapy in patients with non-valvular atrial fibrillation.
Detailed description
This is a prospective, non-randomized, observational cohort study enrolling patients with non-valvular atrial fibrillation (NVAF). Participants will be assigned to one of two groups based on clinical indication. LAAC group: Patients with NVAF undergoing left atrial appendage closure (LAAC) who will receive reduced-dose apixaban (2.5 mg BID) for 3 months, followed by complete withdrawal of antithrombotic therapy. The criterion for anticoagulation discontinuation will be a satisfactory result on transesophageal echocardiography (TEE) or cardiac computed tomography (CT) at 3 months post-implantation, confirming adequate device sealing without significant peri-device leak or device-related thrombosis. Participants will undergo additional TEE or cardiac CT at 6 and 12 months after the procedure and will be followed up by telephone at 18, 24, 30, and 36 months after enrollment. Control group: Patients with NVAF indicated for long-term oral anticoagulation will receive standard full-dose direct oral anticoagulant (DOAC) therapy. Participants in the control group will be followed up by telephone at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Observation period: 36 months. Devices used for LAAC will include the Watchman FLX (Boston Scientific, St. Paul, Minnesota, USA) and the Amplatzer Amulet (Abbott, St. Paul, Minnesota, USA). Primary endpoint: A composite of major bleeding (BARC type ≥3), all-cause mortality, ischemic stroke, systemic embolism, device-related thrombosis (DRT), and significant peri-device leak over 36 months of follow-up. Secondary endpoints: Individual components of the primary composite endpoint over 36 months of follow-up. Propensity score matching will be used to create balanced comparison groups for statistical analysis, adjusting for baseline differences between cohorts.
Interventions
DEVICELeft Atrial Appendage Closure
Percutaneous left atrial appendage closure using Watchman FLX (Boston Scientific) or Amplatzer Amulet (Abbott) devices
DRUGApixaban 2.5 mg BID
Reduced-dose apixaban 2.5 mg BID for 3 months post-LAAC, followed by complete withdrawal of antithrombotic therapy
DRUGStandard-dose DOAC
Standard-dose DOAC therapy (e.g., apixaban 5 mg BID, rivaroxaban 20 mg daily, or other DOAC per physician discretion) continued for the duration of follow-up
Sponsors
National Medical Research Center for Therapy and Preventive Medicine
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years; * Documented nonvalvular AF (≥30 seconds on ECG within previous 12 months); * CHA2DS2-VASc score ≥3 for women and ≥2 for men; * Signed informed consent to participate in the study;
Exclusion criteria
* Active indication for anticoagulation OTHER than atrial fibrillation at the time of enrollment and/or the predicted/unpredicted occurrence of such indications during the entire study period (e.g., mechanical valve, acute VTE, recent PE requiring \>3 months anticoagulation); * Inability to tolerate at least 3 months of apixaban therapy (for LAAC arm); * Indications for antiplatelet therapy or therapy with P2Y12 inhibitors at the time of inclusion and/or the predicted/unpredicted occurrence of such indications during the entire study period; * The presence of mechanical prosthetic heart valves, mitral stenosis of severe or moderate degree; * Active DVT requiring anticoagulation; * Congenital or acquired haemostasis disorders, rheumatic heart disease or recurrent deep vein thrombosis; * Left ventricular ejection fraction (LVEF) \< 30%; * Glomerular filtration rate (GFR) \< 30 ml/min (stage IV or V chronic kidney disease) or dialysis patient; * Severe liver failure, including cirrhosis and Child-Pugh Class C/D; * NYHA class IV congestive heart failure; * The patient had a myocardial infarction - MI with or without ST segment elevation (STEMI, NSTEMI) with or without intervention, within 30 days before LAAC; * The patient had a stroke (of any cause, ischemic or hemorrhagic) within 30 days before LAAC; * Intracardiac thrombus before LAAC; * Major bleeding according to BARC criteria (type 3 and higher) within 30 days before LAAC or before randomization; * Amyloid cardiomyopathy; * Platelet count \< 100,000 x 109/l; * The patient participates in another study, with the exception of observational studies without therapeutic interventions; * Pregnant or breast-feeding patients, patients planning pregnancy during the study period; * The LAAC procedure was unsuccessful or interrupted for technical reasons; * PDL (peridevice leak) ≥ 3 mm; * Contraindications for one of the treatment regimens prescribed by the study protocol (including allergic reactions); * Planned cardiac or non-cardiac surgical procedure within 30 days before or 90 days after LAAC. Minor procedures not requiring discontinuation of antithrombotic therapy are permitted (e.g., cardioversion, catheter ablation, cataract surgery); * The patient has a heart tumor, active infection, signs of physiological tamponade; * The documented life expectancy of the patient is less than 12 months;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of major adverse events | 36 months from enrollment | Composite endpoint including: bleeding events (BARC type ≥3), all-cause death, ischemic stroke, systemic embolism, device-related thrombosis (DRT), and peri-device leak (\>3 mm) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major bleeding events | 36 months from enrollment | Incidence of bleeding events classified as BARC type 3 or higher |
| All-cause mortality | 36 months from enrollment | Incidence of death from any cause |
| Ischemic stroke | 36 months from enrollment | Incidence of ischemic cerebrovascular events confirmed by imaging |
| Systemic embolism | 36 months from enrollment | Incidence of systemic embolic events excluding stroke |
| Device-related thrombosis | 36 months from enrollment | Incidence of thrombus formation on the LAAC device detected by imaging (LAAC group only) |
| Peri-device leak | 36 months from enrollment | Incidence of peri-device leak \>3 mm detected by transesophageal echocardiography or cardiac CT (LAAC group only) |
Countries
Russia
Contacts
CONTACTTimofey Brontveyn, Medical doctor
CONTACTKarapet Davtyan, Professor
PRINCIPAL_INVESTIGATORKarapet Davtyan, Professor
Federal State Budgetary Institution National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthсare of the Russian Federation
Outcome results
None listed