Comparative Efficacy and Safety of Acetylsalicylic Acid and Clopidogrel in Atrial Fibrillation Patients Post-Left Atrial Appendage Closure

The primary objective of the study titled "Optimal Antiplatelet Treatment to Achieve Stroke Avoidance and Fall in Bleeding Events following Left Atrial Appendage Closure (SAFE-LAAC)" is to evaluate the **safety** and **efficacy** of different antiplatelet treatment strategies in patients with **atrial fibrillation** who have undergone left atrial appendage closure (LAAC). Specifically, the study aims to:

• Compare the safety and efficacy 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 in a randomized comparison.
• Compare the safety and efficacy of chronic SAPT beyond 6 months post-procedure versus the discontinuation of all antiplatelet treatment 6 months after LAAC in a non-randomized comparison.

The clinical relevance of this study lies in optimizing antiplatelet therapy to reduce the risk of stroke and bleeding events in patients with atrial fibrillation post-LAAC, potentially improving patient outcomes and guiding clinical practice.

The clinical trial involves participants diagnosed with **atrial fibrillation**. The study population includes both male and female subjects, aged 18 years and older. Participants are generally in a stable health condition, having undergone successful percutaneous left atrial appendage occlusion with either Amplatzer or WATCHMAN devices within 37 days prior to randomization. They have been treated with dual antiplatelet therapy, specifically aspirin and clopidogrel, since the procedure. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are required to comply with all aspects of the protocol, including the assigned treatment strategy and follow-up visits, and must provide written informed consent. Lifestyle considerations such as diet and physical activity 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** who have undergone successful percutaneous left atrial appendage occlusion. 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 post-procedure versus discontinuation of all antiplatelet treatment after 6 months.

The trial is expected to run until December 31, 2027, with participant involvement lasting up to 6 months, depending on the assigned treatment group. The study includes several key visits: an initial screening visit to confirm eligibility, randomization, and baseline assessments; follow-up visits at 30 days, 3 months, and 6 months post-procedure to monitor treatment adherence, collect safety and efficacy data, and assess any adverse events; and an end-of-study visit to finalize data collection and ensure participant safety. Participants may be withdrawn from the study early if they experience significant adverse events, are unable to comply with the study protocol, or withdraw consent.

Inclusion criteria require participants to be at least 18 years old, have undergone successful left atrial appendage occlusion with specific devices, and be on DAPT since the procedure. The primary endpoint focuses on major adverse cardiac and cerebrovascular events, including stroke, transient ischemic attack, peripheral embolism, nonfatal myocardial infarction, cardiovascular and overall mortality, device-related thrombosis, and moderate to severe bleeding events. The trial is categorized as low intervention, as the investigational medicinal products are used in accordance with their marketing authorization, and additional procedures pose minimal risk compared to standard clinical practice.

The clinical trial involves the administration of **acetylsalicylic acid**, a chemical compound commonly known as aspirin, which is utilized in the study as an experimental medication. The pharmaceutical form of acetylsalicylic acid is a tablet, and it is administered orally. The dosage is set at a maximum daily dose of 75 mg, with the treatment period extending up to 70 days. This medication is classified under anticoagulants and platelet aggregation inhibitors, excluding heparin, with an ATC code of B01AC-06. The trial aims to evaluate the safety and efficacy of this treatment regimen in the context of the study's objectives.

Another experimental medication used in the trial is **clopidogrel**, also a chemical compound, administered in tablet form. Clopidogrel is given orally with a maximum daily dose of 75 mg, similar to acetylsalicylic acid. However, the maximum treatment period for clopidogrel is limited to 6 months. This medication is also categorized under anticoagulants and platelet aggregation inhibitors, excluding heparin, with an ATC code of B01AC-0. The trial seeks to assess the comparative effectiveness of clopidogrel in achieving the study's primary objectives.

Both medications are part of a randomized comparison to evaluate the safety and efficacy of early dual antiplatelet therapy (DAPT) discontinuation at 30 days post-procedure, followed by single antiplatelet therapy (SAPT) up to 6 months, versus a 6-month post-procedural DAPT regimen. Additionally, the trial includes a non-randomized comparison of chronic SAPT beyond 6 months post-procedure versus the discontinuation of all antiplatelet treatment 6 months after left atrial appendage closure (LAAC). Participant compliance with the dosing schedules will be monitored throughout the study to ensure adherence to the treatment protocols.

Efficacy in the clinical trial titled "Optimal Antiplatelet Treatment to Achieve Stroke Avoidance and Fall in Bleeding Events following Left Atrial Appendage Closure (SAFE-LAAC)" will be assessed using the primary endpoint of major adverse cardiac and cerebrovascular events (MACCE). This includes the evaluation of **stroke**, transient ischemic attack (TIA), peripheral embolism, nonfatal myocardial infarction, cardiovascular and overall mortality, and device-related thrombosis. Additionally, safety will be assessed by monitoring moderate and severe bleedings classified as type 2-5 according to the Bleeding Academic Research Consortium (BARC) criteria.

The trial aims to compare the safety and efficacy 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. Furthermore, it will compare the safety and efficacy of chronic SAPT beyond 6 months post-procedure with the discontinuation of all antiplatelet treatment 6 months after left atrial appendage closure (LAAC). The trial is designed as a randomized comparison for the first objective and a non-randomized comparison for the second.