What is the optimal antithrombotic strategy in patients with atrial fibrillation having acute coronary syndrome or undergoing percutaneous coronary intervention?

The primary objective of this study is to evaluate the **bleeding risk** (i.e., safety) and **ischemic risk** (i.e., efficacy) associated with a 30-day dual antiplatelet therapy (DAPT) compared to standard therapy at 6 weeks following successful percutaneous coronary intervention (PCI) in patients with **atrial fibrillation** (AF). This is clinically relevant as it aims to optimize antithrombotic strategies in patients with AF undergoing PCI, potentially reducing adverse events and improving patient outcomes.

Secondary objectives include:

• Assessing bleeding and ischemic risks with 30-day DAPT compared to standard therapy at 6 months post-PCI in patients with AF.
• Conducting an exploratory analysis of the individual components of the main secondary endpoint and evaluating quality of life.

The clinical trial involves participants diagnosed with **atrial fibrillation**, **acute coronary syndrome**, or **chronic coronary syndrome**. The study population includes both male and female subjects aged 18 years and older, who have undergone successful percutaneous coronary intervention (PCI). Participants have either a history of or a newly diagnosed atrial fibrillation or flutter within 72 hours after PCI or acute coronary syndrome, with a long-term indication for oral anticoagulation therapy lasting at least one year. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the optimal **antithrombotic** strategy in patients with **atrial fibrillation** who are experiencing acute coronary syndrome or undergoing percutaneous coronary intervention. This is a randomized, double-blind, controlled trial with an estimated duration from November 2022 to November 2026. The trial aims to assess both the safety and efficacy of a 30-day dual antiplatelet therapy (DAPT) compared to standard therapy at 6 weeks post-procedure. The primary safety endpoint is the incidence of major or clinically relevant non-major bleeding, while the co-primary efficacy endpoint includes a composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), successful PCI, and a history or recent diagnosis of atrial fibrillation or flutter. Follow-up visits will occur at 6 weeks and 6 months post-PCI to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 6 months. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety.

The trial involves the administration of various oral medications, including **acetylsalicylic acid**, **edoxaban**, **prasugrel**, **clopidogrel**, and **ticagrelor**, each with specific dosing regimens and treatment periods. The study will ensure that all participants receive appropriate care and monitoring throughout the trial duration, adhering to the highest standards of clinical research methodology.

The clinical trial involves the administration of several **experimental medications** and **non-experimental treatments**. The first experimental medication is **Aspirin 75mg Gastro-resistant Tablets**, containing the active substance **acetylsalicylic acid**. This medication is provided in the form of gastro-resistant tablets and is administered orally. The maximum daily dose is 300 mg, with a total dose of 75 mg per administration. The treatment period is limited to 30 days. Aspirin is classified as an antiplatelet drug and is manufactured by Bristol Laboratories Limited.

Another experimental medication used in the trial is **Lixiana**, available in two dosages: 30 mg and 60 mg film-coated tablets. The active substance in both formulations is **edoxaban**. These tablets are administered orally, with a maximum daily dose of 60 mg. The treatment period can extend up to 999 days. Lixiana is produced by Daiichi Sankyo Europe GmbH and is used as a comparator in the trial.

The trial also includes **Prasugrel 5 mg film-coated tablets**, containing the active substance **prasugrel**. This medication is administered orally, with a maximum daily dose of 10 mg. The treatment period is up to 12 months. Prasugrel is classified as an antiplatelet drug and is manufactured by MSN Laboratories Europe Ltd.

**Clopidogrel Viatris 75 mg film-coated tablets** are also part of the trial, with **clopidogrel** as the active substance. These tablets are administered orally, with a maximum daily dose of 150 mg. The treatment period is up to 12 months. Clopidogrel is an antiplatelet drug produced by Viatris Limited.

Lastly, the trial includes **Ticagrelor Micro Labs 90 mg film-coated tablets**, containing the active substance **ticagrelor**. This medication is administered orally, with a maximum daily dose of 180 mg. The treatment period is up to 12 months. Ticagrelor is classified as an antiplatelet drug and is manufactured by Micro Labs GmbH.

The efficacy of the clinical trial will be assessed by evaluating the **ischemic risk** associated with a 30-day dual antiplatelet therapy (DAPT) compared to standard therapy at 6 weeks following successful percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). The co-primary efficacy endpoint is a composite measure that includes all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis at 6 weeks post-PCI. These endpoints will be measured and collected at the specified timepoint of 6 weeks after PCI.

Secondary efficacy assessments will include the primary safety and efficacy outcomes at 6 months after successful PCI. Additionally, exploratory analyses will be conducted on the individual components of the main secondary endpoint. The net clinical benefit will be evaluated, comprising major bleeding, myocardial infarction, stroke, systemic embolism, all-cause death, and stent thrombosis. Quality of life will also be assessed as part of the secondary endpoints. The data collection and analysis will adhere to the predefined schedule and methodologies to ensure the reliability and validity of the efficacy outcomes.