Comparative Study of Antithrombotic Strategies: Apixaban, Edoxaban, Rivaroxaban, and Acetylsalicylic Acid in Post-Transcatheter Aortic Valve Implantation for Aortic Stenosis

The primary objective of this study is to conduct a pragmatic randomized controlled trial to assess the optimal **antithrombotic** strategy in patients undergoing transcatheter aortic valve implantation for **aortic stenosis**. This is clinically relevant as determining the most effective antithrombotic regimen can significantly impact patient outcomes by reducing the risk of thromboembolic events and bleeding complications following the procedure.

The clinical trial focuses on patients with **aortic stenosis** who have undergone successful transcathter aortic valve implantation (TAVI). The study population includes both male and female participants aged between 65 and 80 years. Participants are expected to be in general good health, as indicated by their ability to comply with the study protocol. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Key lifestyle considerations such as diet, physical activity, or habits are not specified. Participants were selected based on their successful TAVI procedure, age criteria, and their ability to provide informed consent and adhere to the study protocol.

The clinical trial is designed to evaluate the optimal **antithrombotic** strategy in patients with **aortic stenosis** undergoing transcatheter aortic valve implantation (TAVI). This is a pragmatic, randomized, controlled trial with a double-blind design to ensure unbiased results. The trial will compare the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) such as **apixaban**, **edoxaban**, and **rivaroxaban** against **acetylsalicylic acid**. The trial is expected to last until May 31, 2026, with recruitment having started on January 4, 2022.

Participants will be involved in the study for a maximum treatment period of 12 months. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age (65-80 years), successful TAVI, and signed informed consent. Follow-up visits will be scheduled to monitor the primary endpoints, which include hypo-attenuated leaflet thickening and a safety composite of bleeding, thromboembolic events, and all-cause mortality. Secondary endpoints will assess clinical efficacy and long-term outcomes, including major adverse cardiovascular events.

The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted. Participants may be terminated early from the study if they experience significant adverse events, fail to comply with the protocol, or withdraw consent. The trial aims to provide comprehensive data on the safety and efficacy of the antithrombotic strategies in this patient population, contributing to improved clinical guidelines for managing patients post-TAVI.

The clinical trial involves the administration of several **anticoagulant** medications, each with specific dosing regimens and pharmaceutical forms. **Apixaban** is provided in tablet form and is administered orally. The maximum daily dose is 5 mg, with a total maximum dose of 1825 mg over a 12-month period. Another formulation of Apixaban is also used, with a maximum daily dose of 10 mg and a total maximum dose of 3650 mg over the same period. Both formulations are used as approved anticoagulants in the study.

**Edoxaban** is administered as a film-coated tablet, also taken orally. The trial includes two dosing regimens for Edoxaban: one with a maximum daily dose of 30 mg and a total maximum dose of 10950 mg, and another with a maximum daily dose of 60 mg and a total maximum dose of 21900 mg, both over a 12-month period. Edoxaban serves as an approved anticoagulant in the trial.

**Rivaroxaban** is included in the study in two different formulations. The first is a capsule form with a maximum daily dose of 20 mg and a total maximum dose of 7300 mg over 12 months. The second formulation is a hard capsule with a maximum daily dose of 15 mg and a total maximum dose of 5475 mg over the same period. Both formulations are administered orally and are used as approved anticoagulants.

In addition to the experimental anticoagulants, the trial includes **Acetylsalicylic Acid** as a comparator treatment. This medication is provided in tablet form and is administered orally. The maximum daily dose is 75 mg, with a total maximum dose of 27375 mg over a 12-month period. Acetylsalicylic Acid is used as an antiplatelet drug in the study.

All medications are administered orally, and participant compliance is monitored throughout the trial. The study aims to assess the optimal antithrombotic strategy in patients undergoing transcatheter aortic valve implantation for aortic stenosis. The trial is designed to ensure that all participants receive the appropriate dosing regimen for the duration of the study, with careful monitoring to ensure adherence to the treatment protocol.

The efficacy of the clinical trial titled "AntiCoagulation versus AcetylSalicylic Acid after Transcatheter Aortic Valve Implantation" will be assessed using both primary and secondary endpoints. The primary endpoints include **hypo-attenuated leaflet thickening** with a focus on superiority, and a safety composite endpoint evaluating non-inferiority in terms of bleeding, thromboembolic events, and all-cause mortality. Secondary endpoints will further evaluate clinical efficacy through a composite measure of freedom from all-cause mortality, stroke, hospitalization for procedure- or valve-related causes, and a decline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score. Additional secondary endpoints include superiority assessments of thromboembolic events, bleeding events according to VARC-3 definitions, all-cause mortality, and safety outcomes in the safety population. Long-term outcomes will be assessed at 5 and 10 years, focusing on major adverse cardiovascular events (MACE), including cardiac death, aortic valve re-intervention, stroke, myocardial infarction, heart failure hospitalization, and major, life-threatening, or disabling bleeding.