Comparison of Single Versus Dual Antiplatelet Therapy with Acetylsalicylic Acid and Clopidogrel in Atrial Fibrillation Patients Undergoing Percutaneous Left Atrial Appendage Closure

The primary objective of the ARMYDA-AMULET study is to demonstrate that the strategy with **single antiplatelet therapy** (SAPT) is not inferior to the current standard dual antiplatelet therapy (DAPT) following percutaneous left atrial appendage closure in terms of the cumulative incidence of the net composite endpoint, which includes death, thrombotic complications, and bleeding events, at 6 months. This is clinically relevant as it may offer a safer alternative with potentially fewer bleeding complications for patients with atrial fibrillation undergoing this procedure.

Secondary objectives include evaluating whether SAPT use is associated with a similar incidence of ischemic events and a significantly lower incidence of bleeding complications compared to DAPT at 6 months. This assessment is crucial for optimizing antiplatelet therapy strategies to enhance patient outcomes while minimizing adverse effects.

The clinical trial involves **patients with atrial fibrillation** undergoing percutaneous left atrial appendage closure with the Amulet device. The study population includes both male and female participants aged 18 years and older. Participants are required to have documented non-valvular atrial fibrillation, regardless of its type, and a CHA2DS2-VASc score of 2 or higher. They must be suitable for treatment with aspirin and clopidogrel and considered unsuitable for long-term oral anticoagulant therapy due to a high bleeding risk. The trial does not include a vulnerable population. Participants are expected to be available for scheduled 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 efficacy of single antiplatelet therapy (SAPT) compared to dual antiplatelet therapy (DAPT) in patients with **atrial fibrillation** undergoing percutaneous left atrial appendage closure with the Amulet device. This is a multicenter, randomized, double-blind, controlled study. The trial aims to demonstrate that SAPT is not inferior to DAPT regarding the cumulative incidence of a net composite endpoint, including death, thrombotic complications, and bleeding events, over a period of six months. The trial is expected to run from October 2021 to September 2025.

Participants will be randomly assigned to receive either SAPT or DAPT. The study involves several key visits: an initial screening visit to confirm eligibility, follow-up visits at three and six months to assess primary and secondary endpoints, and an end-of-study visit. The primary endpoint is the six-month incidence of the net composite endpoint, while secondary endpoints include device-related thrombus (DRT) at three and six months, any-cause death, incidence of ischemic stroke or systemic embolic events, and bleeding events classified by the BARC system.

Participant involvement is expected to last for the duration of the trial, approximately six months. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of **CARDIOASPIRIN 100 mg** gastro-resistant tablets, which contain the active substance **acetylsalicylic acid**. This medication is provided in the form of a gastro-resistant tablet, designed to prevent the release of the active ingredient in the stomach, thereby minimizing gastric irritation. The dosage for this trial is set at 100 mg per tablet, with a maximum daily dose of 300 mg. The administration route is oral, and the treatment period is limited to a maximum of 1 day. The product is manufactured by Bayer SPA and is not a pediatric formulation.

Another treatment used in the study is **CARDIOASPIRIN 100 mg** gastro-resistant tablets, also containing **acetylsalicylic acid**. This formulation is identical in pharmaceutical form and active substance to the previously mentioned CARDIOASPIRIN, but it is administered at a dosage of 100 mg per day, with a maximum treatment period of 6 months. The administration route remains oral, and the product is also manufactured by Bayer SPA.

The trial also includes the use of **Plavix 300 mg** film-coated tablets, which contain the active substance **clopidogrel**. This medication is provided in a film-coated tablet form, which aids in the protection of the active ingredient until it reaches the intestines. The dosage is set at 300 mg per tablet, with a maximum daily dose of 300 mg. The administration route is oral, and the treatment period is limited to a maximum of 1 day. The product is manufactured by Sanofi Winthrop Industrie and is not a pediatric formulation.

Additionally, **Plavix 75 mg** film-coated tablets are used in the study, also containing **clopidogrel**. This formulation is similar in pharmaceutical form to the 300 mg Plavix tablets but is administered at a dosage of 75 mg per day, with a maximum treatment period of 3 months. The administration route is oral, and the product is manufactured by Sanofi Winthrop Industrie. This formulation is also not intended for pediatric use.

Efficacy in the clinical trial titled "Head-to-head compaRison of single versus dual antiplatelet treatMent strategY after percutaneous left atrial appenDage closure: A MULticenter, randomizEd sTudy. The ARMYDA-AMULET study" will be assessed by evaluating the cumulative incidence of a net composite endpoint. This endpoint includes all-cause death, thrombotic complications, and bleeding events over a period of 6 months. The primary endpoint will specifically measure the 6-month incidence of these events in two treatment arms: single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT).

Secondary endpoints will include the incidence of device-related thrombosis (DRT) at 3 and 6 months, any-cause death, ischemic stroke, systemic embolic events (SEE), and bleeding events classified by the Bleeding Academic Research Consortium (BARC) classification of grade 3 or higher. These parameters will be assessed at both 3 and 6 months using transesophageal echocardiography (TEE) and other relevant clinical evaluations. The trial aims to demonstrate that SAPT is not inferior to DAPT in terms of these efficacy measures following left atrial appendage closure.