Evaluation of Oral Anticoagulation with Apixaban, Rivaroxaban, and Dabigatran Etexilate in New-Onset Post-Operative Atrial Fibrillation Post-CABG

The primary objective of this study is to assess the **effectiveness** and **safety** of adding oral anticoagulation (OAC) to background antiplatelet therapy in patients who develop new-onset post-operative atrial fibrillation (POAF) following isolated coronary artery bypass grafting (CABG) surgery. The effectiveness is measured by the prevention of thromboembolic events, while safety is evaluated by the incidence of major bleeding. This is clinically relevant as it addresses the risk of thromboembolic complications, which are a significant concern in patients with new-onset POAF after CABG, and evaluates the balance between reducing these risks and the potential for increased bleeding.

Secondary objectives include evaluating the burden of atrial fibrillation 30 days post-discharge using continuous monitoring devices in patients who have developed new-onset POAF after CABG. This aim will be addressed in an ancillary study, which is not currently being conducted at European trial sites.

The clinical trial involves a total of **2450 participants** who are being studied for the effectiveness and safety of adding oral anticoagulation to antiplatelet therapy in patients with **new-onset post-operative atrial fibrillation (POAF)** after isolated coronary artery bypass grafting (CABG). The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on their recent experience of isolated CABG for coronary artery disease and the development of POAF that persists for more than 60 minutes or is recurrent within 7 days post-surgery. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The selection criteria ensure that the study focuses on individuals who have undergone a specific surgical procedure and developed a particular post-operative condition, providing a targeted approach to evaluating the trial's objectives.

The clinical trial is designed to evaluate the effectiveness and safety 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 grafting (CABG) surgery. This trial is a randomized, double-blind, controlled study with a primary focus on preventing thromboembolic events and assessing major bleeding risks. The trial is categorized as a phase IV, low interventional clinical trial, with the use of investigational medicinal products (IMPs) being evidence-based and supported by published scientific evidence.

The trial is expected to run from February 10, 2023, to February 27, 2026. Participants will be involved for a maximum treatment period of 90 days. The study includes several key visits: an initial screening visit to confirm eligibility, follow-up visits at 90 and 180 days post-randomization to assess primary and secondary endpoints, and an end-of-study visit to conclude participation. The primary endpoints include a composite of death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism, or venous thromboembolism (VTE), as well as bleeding events classified by the Bleeding Academic Research Consortium (BARC) type 3 or 5.

Participants are expected to be involved for the duration of the trial unless they meet conditions for early termination, such as experiencing adverse events that compromise safety or failing to adhere to the study protocol. The trial aims to provide insights into the net clinical benefit of the treatment strategy, with secondary endpoints including cardiovascular and non-cardiovascular mortality, incidence of BARC 2 bleeding, and patient satisfaction surveys. The trial's design ensures rigorous assessment of both the effectiveness and safety of the treatment regimen in a controlled environment.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. **Clopidogrel ratiopharm 75 mg film-coated tablets** are used as a comparator. The active substance is **clopidogrel**, a chemical compound, administered orally. The maximum daily dose is 75 mg, with a total dose not exceeding 6750 mg over a 90-day period.

**Eliquis 2.5 mg film-coated tablets** contain the active substance **apixaban**. This medication is administered orally with a maximum daily dose of 60 mg and a total dose of 5400 mg over the course of 90 days. It serves as a test medication in the trial.

**Brilique 60 mg film-coated tablets** are another test medication, containing **ticagrelor** as the active substance. The oral administration allows for a maximum daily dose of 90 mg, with a total dose of 8100 mg over 90 days.

**Xarelto 10 mg film-coated tablets** are used as a comparator, with **rivaroxaban** as the active substance. The oral route of administration permits a maximum daily dose of 30 mg, with a total dose of 2700 mg over 90 days.

**Pradaxa 75 mg hard capsules** contain **dabigatran etexilate** and are administered orally. This test medication allows for a maximum daily dose of 600 mg, with a total dose of 54000 mg over 90 days.

**Lixiana 15 mg film-coated tablets** are administered orally, containing **edoxaban** as the active substance. The maximum daily dose is 60 mg, with a total dose of 5400 mg over 90 days, serving as a test medication.

**Marcumar 3 mg tablets** contain **phenprocoumon** and are administered orally. The maximum daily dose is 9 mg, with a total dose of 810 mg over 90 days, used as a comparator in the trial.

**Aspirin 500 mg coated tablets** contain **acetylsalicylic acid** and are administered orally. The maximum daily dose is 325 mg, with a total dose of 29250 mg over 90 days, serving as a comparator.

All medications are administered orally, and participant compliance is monitored throughout the trial to ensure adherence to dosing schedules. The trial aims to evaluate the effectiveness and safety of these medications in preventing thromboembolic events and managing bleeding risks in patients with new-onset post-operative atrial fibrillation following coronary artery bypass graft surgery.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary effectiveness endpoint is a composite measure that includes death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), systemic arterial thromboembolism, or venous thromboembolism (VTE), which encompasses deep venous thrombosis (DVT) and/or pulmonary embolism (PE). The primary safety endpoint is defined by the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding events.

Secondary endpoints will further evaluate the trial's efficacy and safety. These include the composite of death, ischemic stroke, TIA, MI, or systemic arterial thromboembolism, net clinical benefit (NCB), and the incidence of the primary effectiveness and safety endpoints at 180 days post-randomization. Additionally, individual components of the primary endpoints will be assessed at 90 and 180 days, along with cardiovascular and non-cardiovascular mortality, incidence of BARC 2 bleeding, and cardiac arrhythmias, including recurrent symptomatic or asymptomatic **atrial fibrillation** (AF) requiring medical attention at these timepoints.

Other secondary measures include the length of stay during the index hospitalization, number and reasons for readmissions at 90 and 180 days, hospital resource utilization at 180 days, and patient convenience and satisfaction, which will be evaluated using the Perception of Anticoagulation Treatment Questionnaire (PACT-Q2) at 90 days post-randomization. These assessments will provide a comprehensive evaluation of the trial's efficacy in preventing thromboembolic events and managing bleeding risks in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting (CABG).