Evaluation of P2Y12 Inhibitor Monotherapy Followed by Direct Oral Anticoagulant in Atrial Fibrillation Patients Post-Sirolimus-Eluting Stent Implantation

The primary objective of this study is to evaluate the **safety** and **efficacy** of a P2Y12 inhibitor monotherapy regimen followed by a direct-acting oral anticoagulant (DOAC) monotherapy in patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) with sirolimus-eluting Supraflex Cruz stent implantation. The safety assessment focuses on the incidence of major or clinically relevant non-major bleeding events, while the efficacy assessment targets the occurrence of major adverse cardiac and cerebral events. This regimen is compared to the current standard of care, which involves triple antithrombotic therapy (aspirin, P2Y12 inhibitor, and DOAC) for up to one month, followed by dual antithrombotic therapy (P2Y12 inhibitor and DOAC) for 6 to 12 months, and subsequent DOAC monotherapy. The study's clinical relevance lies in potentially optimizing antithrombotic therapy to reduce bleeding risks while maintaining efficacy in preventing thromboembolic events in AF patients post-PCI.

The clinical trial involves a total of **1350 participants** who are **AF patients** that have undergone successful **PCI**. The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on specific criteria, including a diagnosis of **atrial fibrillation** or flutter with an indication for oral anticoagulation using direct-acting oral anticoagulants (DOACs) for at least 12 months, and a successful percutaneous coronary intervention in at least one lesion within the previous seven days. The trial excludes any individuals with major adverse events post-qualifying PCI, such as new-onset chest pain suspected to be of ischemic origin, acute or subacute stent thrombosis, or new-onset neurological signs or symptoms. Participants are required to provide written informed consent. The trial does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The sponsor has not provided additional information regarding the general health status or habits of the participants.

The clinical trial is designed to evaluate the safety and efficacy of a **P2Y12 inhibitor** monotherapy regimen followed by a direct-acting oral anticoagulant (DOAC) in patients with **atrial fibrillation** (AF) who have undergone successful percutaneous coronary intervention (PCI). The study employs a randomized, double-blind, controlled design to compare the investigational regimen against the current standard of care, which includes triple antithrombotic therapy for up to one month, followed by dual antithrombotic therapy for 6 to 12 months, and DOAC monotherapy thereafter. The trial is expected to last for a total duration of 15 months, with participant involvement spanning the same period.

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), a diagnosis of atrial fibrillation or flutter with an indication for oral anticoagulation, and successful PCI within the previous 7 days. Following the screening, participants will be randomized and commence the treatment phase. Follow-up visits will be scheduled at regular intervals to monitor safety and efficacy outcomes, including major adverse cardiac or cerebral events and bleeding events as defined by the International Society of Thrombosis and Hemostasis (ISTH) criteria. The end-of-study visit will conclude the trial, assessing the primary and secondary endpoints, such as the composite of death from any cause, myocardial infarction, stroke, or non-CNS systemic embolism.

Participant involvement is expected to last for the entire 15-month duration of the trial unless early termination is warranted. Conditions that may lead to early termination include the occurrence of major adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial aims to provide comprehensive data on the safety and efficacy of the investigational treatment regimen, contributing to the optimization of therapeutic strategies for AF patients undergoing PCI.

The clinical trial involves the administration of several **experimental medications** and comparator treatments to evaluate their safety and efficacy in patients with atrial fibrillation undergoing coronary stent implantation. **Clopidogrel** is administered as a film-coated tablet with a maximum daily dose of 75 mg. It is taken orally and is classified as an anti-platelet agent. The treatment period for clopidogrel is up to 12 months.

**Acetylsalicylic acid** is provided in the form of a gastro-resistant capsule, with a maximum daily dose of 100 mg. This anti-platelet medication is also administered orally, but its treatment period is limited to 1 month.

**Rivaroxaban** is another experimental medication used in this trial. It is available as a film-coated tablet with a maximum daily dose of 20 mg. Rivaroxaban is an anticoagulant taken orally, with a treatment duration of up to 12 months.

**Dabigatran** is administered in a hard capsule form, with a maximum daily dose of 300 mg. This oral anticoagulant is used for a treatment period of up to 11 months.

**Edoxaban** is provided as a film-coated tablet, with a maximum daily dose of 60 mg. It is an oral anticoagulant with a treatment period of up to 12 months.

**Apixaban** is administered as a film-coated tablet, with a maximum daily dose of 10 mg. This oral anticoagulant is used for a treatment period of up to 12 months.

**Prasugrel** is available as a film-coated tablet, with a maximum daily dose of 10 mg. It is an anti-platelet agent taken orally, with a treatment period of up to 6 months.

**Ticagrelor** is administered as a film-coated tablet, with a maximum daily dose of 180 mg. This anti-platelet medication is taken orally, with a treatment period of up to 6 months.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to compare the efficacy and safety of these medications in reducing major adverse cardiac and cerebral events, as well as bleeding risks, in the specified patient population.

The efficacy of the clinical trial will be assessed by evaluating the occurrence of **major adverse cardiac or cerebral events (MACCE)** and **major or clinically relevant non-major bleeding (MCB)**. The primary endpoints include the composite of death from any cause, myocardial infarction, stroke, or non-CNS systemic embolism, as well as bleeding events defined according to the International Society of Thrombosis and Hemostasis (ISTH) criteria. These events will be monitored from randomization up to 12 months.

Secondary endpoints will further dissect the primary endpoints into individual components and additional composites, such as death from cardiovascular causes, myocardial infarction, stroke, and non-CNS systemic embolism. Other secondary measures include hospitalization rates, stent thrombosis, revascularization events, and all bleeding events adjudicated according to BARC, TIMI, or GUSTO scales. Transfusion rates will also be evaluated in patients with or without clinically detected overt bleeding.

The trial will follow a structured schedule for data collection and analysis, ensuring that all relevant events are captured and assessed over the 15-month follow-up period. The efficacy assessments will be conducted using standardized criteria and validated scales to ensure consistency and reliability in the evaluation of the therapeutic strategy's impact on patients with atrial fibrillation undergoing percutaneous coronary intervention.