Comparative Efficacy and Safety of Dual vs. Single Antiplatelet Therapy Post-Left Atrial Appendage Closure in End-Stage Renal Disease Patients

The primary objective of this study is to evaluate the **safety** and **efficacy** of different antiplatelet treatment strategies following left atrial appendage closure in patients with end-stage renal disease on chronic dialysis. Specifically, the study aims to compare the outcomes of early dual antiplatelet therapy (DAPT) discontinuation at 30 days post-procedure with the continuation of single antiplatelet therapy (SAPT) up to 6 months, versus 6 months of post-procedural DAPT. Additionally, it seeks to compare the safety and efficacy of chronic SAPT beyond 6 months post-procedure with the discontinuation of all antiplatelet treatment 6 months after the procedure. These comparisons are clinically relevant as they may inform optimal antiplatelet management strategies to minimize stroke risk and bleeding events in this high-risk population.

Secondary objectives include the assessment of the safety and efficacy of transcatheter left atrial appendage occlusion in patients with end-stage renal disease on chronic dialysis, utilizing a retrospective registry approach. This evaluation is crucial for understanding the broader implications of the procedure in this specific patient group.

The clinical trial involves participants diagnosed with **Atrial Fibrillation** who are also experiencing end-stage renal disease and are undergoing chronic dialysis. The study population includes both male and female subjects aged 18 years and older. Participants are required to have successfully undergone percutaneous left atrial appendage occlusion with either Amplatzer or WATCHMAN devices within 37 days prior to randomization. The trial does not involve a vulnerable population. Participants are expected to comply with all aspects of the protocol, including the assigned treatment strategy and follow-up visits. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the safety and efficacy of antiplatelet treatment strategies in patients with **atrial fibrillation** and end-stage renal disease undergoing chronic dialysis. The trial employs a randomized, double-blind, controlled design to compare two treatment regimens: early discontinuation of dual antiplatelet therapy (DAPT) at 30 days post-procedure with continuation of single antiplatelet therapy (SAPT) up to 6 months, versus 6 months of post-procedural DAPT. Additionally, a non-randomized comparison will assess the safety and efficacy of chronic SAPT beyond 6 months versus discontinuation of all antiplatelet treatment after 6 months.

The trial is expected to last until December 31, 2027, with participant recruitment having commenced on September 28, 2022. Participants will be involved in the study for a maximum of 6 months, with the potential for early termination if they fail to comply with the protocol, experience adverse events, or withdraw consent. The study includes several key visits: an initial screening visit to confirm eligibility, follow-up visits at 30 days, 6 months, and potentially beyond, depending on the treatment arm, and an end-of-study visit to assess outcomes.

Inclusion criteria require participants to have successfully undergone percutaneous left atrial appendage occlusion with specific devices within 37 days prior to randomization, be on chronic dialysis, and be at least 18 years old. The primary endpoint focuses on major adverse cardiac and cerebrovascular events, including stroke, transient ischemic attack, peripheral embolism, nonfatal myocardial infarction, and mortality, as well as device-related thrombosis and bleeding events. Secondary endpoints include individual components of the primary endpoint, any bleeding, new ischemic lesions in the central nervous system, cognitive disorders, thrombosis of the dialysis access, and the efficacy and safety of the left atrial appendage closure in the periprocedural and 1-month follow-up periods.

The clinical trial involves the administration of **acetylsalicylic acid**, a chemical compound used as an experimental medication. This medication is provided in the form of a **tablet** and is administered orally. The dosage is set at a maximum of 75 mg per day, with the treatment period extending up to 70 days. The primary role of acetylsalicylic acid in this trial is to act as a platelet aggregation inhibitor, which is crucial for patients undergoing procedures such as left atrial appendage closure. The administration of this medication is monitored to ensure compliance with the dosing schedule, which is critical for evaluating its efficacy and safety in the context of the study.

Another experimental medication used in the trial is **clopidogrel**, also a chemical compound provided in tablet form. Similar to acetylsalicylic acid, clopidogrel is administered orally with a maximum daily dose of 75 mg. However, the treatment period for clopidogrel is limited to 6 months. Clopidogrel serves as a platelet aggregation inhibitor, and its role in the trial is to assess its effectiveness in combination with or as an alternative to other antiplatelet therapies. The trial includes monitoring of participant compliance with the dosing regimen to ensure accurate assessment of the medication's impact on the study's objectives.

In addition to the experimental medications, the trial may involve the use of standard-of-care therapies, including other anticoagulants and platelet aggregation inhibitors, excluding heparin, as per the ATC code B01AC-06. These non-experimental treatments are used to provide a comparative framework for evaluating the efficacy and safety of the experimental medications. The trial's design includes careful monitoring of all administered treatments to ensure adherence to the protocol and to facilitate accurate data collection for the study's outcomes.

Efficacy in the clinical trial titled "Optimal Antiplatelet Treatment to Achieve Stroke Avoidance and Fall in Bleeding Events following Left Atrial Appendage Closure – Chronic Kidney Disease (SAFE LAAC CKD)" will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on major adverse cardiac and cerebrovascular events (MACCE), which include **stroke**, transient ischemic attack (TIA), peripheral embolism, nonfatal myocardial infarction, cardiovascular and overall mortality, and device-related thrombosis. Safety will be evaluated by monitoring moderate and severe bleedings classified as type 2-5 according to the Bleeding Academic Research Consortium (BARC) criteria.

Secondary endpoints will include the individual components of the composite primary endpoint, as well as any bleeding events, the presence of new intermediate and large ischemic lesions (≥4mm in size) in the central nervous system as assessed by brain MRI, and new cognitive disorders evaluated using the Addenbrooke's Cognitive Examination (ACE-III). Additionally, thrombosis of the dialysis access and the efficacy and safety of left atrial appendage closure (LAAC) during the periprocedural period and at a 1-month follow-up will be assessed.