Anticoagulation for New-Onset Post-Operative Atrial Fibrillation After CABG

Обзор

The primary objective of this study is to evaluate the effectiveness (prevention of thromboembolic events) and safety (major bleeding) of adding oral anticoagulation (OAC) to background antiplatelet therapy in patients who develop new-onset post-operative atrial fibrillation (POAF) after isolated coronary artery bypass graft (CABG) surgery. All patients with a qualifying POAF event, who decline randomization, will be offered the option of enrollment in a parallel registry that captures their baseline risk profile and their treatment strategy in terms of anticoagulants or antiplatelets received. These patients will also be asked to fill out a brief decliner survey.

Подробное описание

This is a prospective, multicenter, open-label, randomized trial comparing OAC with no OAC (1:1 ratio) in patients who develop new-onset POAF after CABG. The primary effectiveness endpoint is the composite of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism or venous thromboembolism (VTE) at 90 days after randomization. The primary safety endpoint is BARC (Bleeding Academic Research Consortium) grade 3 or 5 bleeding at 90 days after randomization. The overall intent is to evaluate the trade-off in prevention of thromboembolic events versus an increase in bleeding.

Patients will be randomly assigned to the following treatment strategies:

* OAC-based strategy (experimental arm): OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant (apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor) * Antiplatelet-only strategy (control arm): single antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)

The protocol-specified duration of anticoagulation is 90 days. Patients, who are randomized to the control arm and develop recurrent AF after 30 days, may be crossed-over to an OAC. Accrual is expected to take 60 months. Study follow-up visits will be performed at 90 days and phone follow-up at days 30, 60, and 180 days.

Data for patients enrolled in the registry will be ascertained from the local clinical site via a review of medical records. The baseline risk profile of registry patients (i.e., patients eligible but unwilling to be randomized) will be analyzed and compared to that of patients randomized in the trial. The usage of anticoagulant and antiplatelet therapies in the registry population overall and baseline CHA2DS2-VASC ischemic stroke risk score will also be determined.

Up to 500 patients will also be offered the option to participate in a digital health substudy which includes a wearable heart rhythm monitor device for 30 days post discharge.

Вмешательства

• Препарат Antiplatelet-only strategy
  Aspirin 75-325 mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)
• Препарат Oral Anticoagulant plus background antiplatelet therapy
  OAC with vitamin K antagonist (VKA) with international normalized ratio (INR) target 2-3 or any approved direct oral anticoagulant OR apixaban, rivaroxaban, edoxaban or dabigatran) in addition to background antiplatelet therapy with aspirin 75-325mg once-daily or a P2Y12-inhibitor (clopidogrel or ticagrelor)

Первичные конечные точки

• Composite of death, ischemic stroke, TIA, MI, systemic arterial thromboembolism or venous thromboembolism (DVT and/or PE) [Срок оценки: up to 180 days after randomization]
• Any BARC type 3 or 5 [Срок оценки: 90 days after randomization]

Вторичные конечные точки (11)

• Net clinical benefit (NCB) [Срок оценки: 90 days after randomization]
• Number of participants with Ischemic Stroke event [Срок оценки: 180 days after randomization]
• Number of participants with TIA event [Срок оценки: 180 days after randomization]
• Number of participants with MI event [Срок оценки: 180 days after randomization]
• Number of participants with systematic arterial thromboembolism event [Срок оценки: 180 days after randomization]
• Number of participants with venous thromboembolism event [Срок оценки: 180 days after randomization]
• Number of cardiovascular mortalities [Срок оценки: up to 180 days after randomization]
• Number of non-cardiovascular mortalities [Срок оценки: up to 180 days after randomization]
• The incidence of BARC 2 bleeding at 90 after randomization [Срок оценки: 90 days after randomization]
• The incidence of BARC 2 bleeding at 180 days after randomization [Срок оценки: 180 days after randomization]
• Number of cardiac arrhythmias [Срок оценки: 180 days after randomization]

Критерии участия

Критерии включения

• Patients of age ≥18 years who undergo isolated CABG for coronary artery disease
• POAF that persists for >60 minutes or is recurrent (more than one episode) within 7 days after the index CABG surgery

Критерии исключения

• Clinical history of either permanent, persistent or paroxysmal atrial fibrillation
• Any pre-existing clinical indication for long-term OAC
• Any absolute contraindication to OAC
• Planned use of post-operative dual antiplatelet therapy (DAPT)

a. This includes, but is not limited to, patients with recent PCI with drug-eluting or bare-metal stent.

• Cardiogenic shock
• Major perioperative complication\* occurring between CABG and randomization

a. including, but not limited to, stroke, TIA, MI, major bleeding (BARC type 4 bleeding), severe sepsis, renal failure requiring dialysis, or need for reoperation due to bleeding (e.g. pericardial tamponade).

• Concomitant left atrial appendage closure during CABG
• Concomitant valve surgery during CABG or prior valve surgery (including aortic, mitral, tricuspid or pulmonary)
• Concomitant mitral valve annuloplasty during CABG
• Concomitant carotid artery endarterectomy during CABG
• Concomitant aortic root replacement during CABG
• Concomitant surgery for AF during CABG
• Liver cirrhosis or Child-Pugh Class C chronic liver disease
• Pharmacologic therapy with an investigational drug or device within 30-days prior to randomization or plan to enroll patient in an investigational drug or device trial during participation in this trial
• Pregnancy at the time of randomization
• Unable or unwilling to provide inform consent
• Unable or unwilling to comply with the study treatment and follow-up
• Existence of underlying disease that limits life expectancy to less than one year

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 51 центр

• CHI St. Vincent, Arkansas — Little Rock
• University of Southern California — Los Angeles
• Cedars-Sinai Medical Center — Los Angeles
• Stanford University — Stanford
• Medical Center of Aurora — Aurora
• Western Connecticut Hospital Systems — Danbury
• Yale Medicine — New Haven
• MedStar Washington Hospital Center — Washington D.C.
• … и ещё 43 центра

Германия · 25 центров

• University Heart Center Hamburg — Berlin
• Heart Center Leipzig — Berlin
• University Medical Center Göttingen — Göttingen
• University Medical Center Jena — Jena
• Kerckhoff Klinik, Bad Nauheim — Bad Nauheim
• Clinic Bad Neustadt - Medical Center for Heart and Vascular Diseases — Bad Neustadt an der Saale
• HDZ-NRW Bad Oeynhausen — Bad Oeynhausen
• Charité Berlin - Benjamin Franklin Campus — Berlin
• … и ещё 17 центров

Великобритания · 17 центров

Список центров уточняется — проверьте первичный протокол.

Канада · 9 центров

• University of Alberta Hospital — Edmonton
• London Health Sciences Centre — London
• Sunnybrook Hospital — Toronto
• Montreal Heart Institute — Montreal
• Centre Hospitalier de l'Université de Montréal — Montreal
• Hôpital du Sacré-Cœur de Montréal — Montreal
• University of Ottawa Heart Institute — Ottawa
• Hôpital Laval — Québec
• … и ещё 1 центр

Бразилия · 4 центра

• Hospital Samaritano Paulista — São Paulo
• Hospital Universitário São Francisco na Providência de Deus — São Paulo
• Instituto de Pesquisa Clínica de Campinas — São Paulo
• Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da USP-InCor-HCFMUS — São Paulo

Публикации

• Budd AN, Kertai MD, Wyler von Ballmoos MC, Raphael J, Ghadimi K, Levy JH, Shore-Lesserson LJ, Mazzeffi MA, Sniecinski RM, Tanaka KA, Bolliger D, Abdalla M, Ural KG, Upchurch PA, Rozental O, Hunter CB, Seibert AR, Klick JC, Carroll D, Lobner K, Hensley NB. Management of Direct Oral Anticoagulants in Adult Patients Undergoing Cardiac Surgery: A Joint Consensus Statement by the Society of Cardiovascu PMID 41609362
• Boriani G, Imberti JF, McIntyre WF, Mei DA, Healey JS, Schnabel RB, Svennberg E, Camm AJ, Freedman B. Detection and management of postoperative atrial fibrillation after coronary artery bypass grafting or non-cardiac surgery: a survey by the AF-SCREEN International Collaboration. Intern Emerg Med. 2025 Apr;20(3):739-749. doi: 10.1007/s11739-025-03861-2. Epub 2025 Feb 8. PMID 39921772
• Taha A, Nielsen SJ, Bergfeldt L, Ahlsson A, Friberg L, Bjorck S, Franzen S, Jeppsson A. New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Outcome: A Population-Based Nationwide Study From the SWEDEHEART Registry. J Am Heart Assoc. 2021 Jan 5;10(1):e017966. doi: 10.1161/JAHA.120.017966. Epub 2020 Nov 30. PMID 33251914

Идентификаторы

NCT: NCT04045665 · GCO 08-1078 · 2U01HL088942-12

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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