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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Composite of major adverse events [Срок оценки: 36 months from enrollment]

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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;

Критерии исключения

• 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;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Россия · 1 центр

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

Публикации

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• 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

Идентификаторы

NCT: NCT07575867 · 03-03/26

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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