CLOT-LESS - CLOsure Tailored: LEss Antithrombotic Strategy After LAAC for Stroke Prevention

Overview

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

• Device Left Atrial Appendage Closure
  Percutaneous left atrial appendage closure using Watchman FLX (Boston Scientific) or Amplatzer Amulet (Abbott) devices
• Drug Apixaban 2.5 mg BID
  Reduced-dose apixaban 2.5 mg BID for 3 months post-LAAC, followed by complete withdrawal of antithrombotic therapy
• Drug Standard-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

Primary outcome measures

• Composite of major adverse events [Time frame: 36 months from enrollment]

Secondary outcome measures (6)

• Major bleeding events [Time frame: 36 months from enrollment]
• All-cause mortality [Time frame: 36 months from enrollment]
• Ischemic stroke [Time frame: 36 months from enrollment]
• Systemic embolism [Time frame: 36 months from enrollment]
• Device-related thrombosis [Time frame: 36 months from enrollment]
• Peri-device leak [Time frame: 36 months from enrollment]

Eligibility criteria

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;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Russia · 1 center

• Federal State Budgetary Institution National Medical Research Center for Therapy and Preve — Moscow

Publications

• Potpara T, Grygier M, Hausler KG, Nielsen-Kudsk JE, Berti S, Genovesi S, Marijon E, Boveda S, Tzikas A, Boriani G, Boersma LVA, Tondo C, De Potter T, Lip GYH, Schnabel RB, Bauersachs R, Senzolo M, Basile C, Bianchi S, Osmancik P, Schmidt B, Landmesser U, Dohner W, Hindricks G, Kovac J, Camm AJ. Practical guide on left atrial appendage closure for the non-implanting physician: an international cons PMID 38291925
• Continisio S, Montonati C, Angelini F, Bocchino PP, Carbonaro C, Giacobbe F, Dusi V, De Filippo O, Ielasi A, Giannino G, Boldi E, Fabris T, D'Ascenzo F, De Ferrari GM, Tarantini G. Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure-A systematic review and meta-analysis. Eur J Clin Invest. 2024 Aug;54(8):e14209. doi: 10.1111/eci.14209. Epub 2024 Apr 10. PMID 38597271
• Kramer A, Korsholm K, Nielsen-Kudsk JE. Single antiplatelet therapy following Amplatzer left atrial appendage occlusion. EuroIntervention. 2024 Mar 4;20(5):e301-e311. doi: 10.4244/EIJ-D-23-00684. PMID 38436367
• Li X, Jin Q, Yao Y, Zhang X, Lv Q. Clinical Effectiveness and Safety Comparison between Reduced Rivaroxaban Dose and Dual Antiplatelet Therapy for Nonvalvular Atrial Fibrillation Patients Following Percutaneous Left Atrial Appendage Closure: A Prospective Observational Study. Rev Cardiovasc Med. 2023 Nov 27;24(11):335. doi: 10.31083/j.rcm2411335. eCollection 2023 Nov. PMID 39076450
• Cepas-Guillen PL, Flores-Umanzor E, Regueiro A, Brugaletta S, Ibanez C, Sanchis L, Sitges M, Rodes-Cabau J, Sabate M, Freixa X. Low Dose of Direct Oral Anticoagulants after Left Atrial Appendage Occlusion. J Cardiovasc Dev Dis. 2021 Oct 28;8(11):142. doi: 10.3390/jcdd8110142. PMID 34821695
• Faroux L, Cruz-Gonzalez I, Arzamendi D, Freixa X, Nombela-Franco L, Peral V, Caneiro-Queija B, Mangieri A, Trejo-Velasco B, Asmarats L, Regueiro A, McInerney A, Mas-Llado C, Estevez-Loureiro R, Laricchia A, O'Hara G, Rodes-Cabau J. Short-term direct oral anticoagulation or dual antiplatelet therapy following left atrial appendage closure in patients with relative contraindications to chronic antic PMID 33647365
• Bergmann MW, Betts TR, Sievert H, Schmidt B, Pokushalov E, Kische S, Schmitz T, Meincke F, Stein KM, Boersma LVA, Ince H. Safety and efficacy of early anticoagulation drug regimens after WATCHMAN left atrial appendage closure: three-month data from the EWOLUTION prospective, multicentre, monitored international WATCHMAN LAA closure registry. EuroIntervention. 2017 Sep 20;13(7):877-884. doi: 10.424 PMID 28606886
• Freixa X, Cruz-Gonzalez I, Cepas-Guillen P, Millan X, Antunez-Muinos P, Flores-Umanzor E, Asmarats L, Regueiro A, Lopez-Tejero S, Li CP, Sanchis L, Rodes-Cabau J, Arzamendi D. Low-Dose Direct Oral Anticoagulation vs Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion: The ADALA Randomized Clinical Trial. JAMA Cardiol. 2024 Oct 1;9(10):922-926. doi: 10.1001/jamacardio.2024.2335. PMID 39110427

Identifiers

NCT: NCT07575867 · 03-03/26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗