Evaluation of Rivaroxaban and Warfarin Sodium in Anticoagulation Management for Acute Coronary Syndrome with Atrial Fibrillation Using Telecardiology

The primary objective of this study is to evaluate the safety of introducing **anticoagulant** treatment in patients with **acute coronary syndrome** (ACS) and de novo **atrial fibrillation** (AF) based on data from an implantable Holter device with remote monitoring. This approach is compared to the systematic introduction of anticoagulant treatment combined with dual antiplatelet therapy (DAPT) based on the CHA2DS2-VASc score. The clinical relevance lies in determining whether this method reduces the occurrence of hemorrhagic events, which is crucial for optimizing treatment strategies in this patient population.

Secondary objectives include demonstrating that the absence of anticoagulant therapy, except in cases of AF recurrence detected by the implantable Holter, does not lead to additional secondary complications during follow-up in patients with ACS and de novo AF. This aspect is significant for assessing the long-term safety and efficacy of withholding anticoagulation in specific scenarios, potentially impacting clinical decision-making and patient management.

The clinical trial involves participants diagnosed with **atrial fibrillation** and **acute coronary syndrome**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have been hospitalized for acute coronary syndrome, with or without ST segment elevation, and must have experienced atrial fibrillation either upon arrival at the hospital or during hospitalization, without any prior known history of arrhythmia. The trial does not include a vulnerable population. Key lifestyle factors such as diet and physical activity are not specified. The sponsor has not provided the total number of participants involved in the trial. Selection criteria include a CHA2DS2-VASc score of at least 1 for men and at least 2 for women, and participants must have undergone coronary angioplasty with stenting during hospitalization. The trial population was selected based on these specific medical and procedural criteria.

The clinical trial is designed to evaluate the safety of anticoagulant therapy in patients with **acute coronary syndrome** and de novo **atrial fibrillation**. This is a prospective, multicenter study with a randomized, double-blind, controlled trial design. The trial will compare the safety of anticoagulant treatment guided by data from an implantable Holter device with remote monitoring against the standard approach based on the CHA2DS2-VASc score. The trial is expected to last until February 2026, with recruitment starting in September 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥18 years), hospitalization for acute coronary syndrome, and the presence of atrial fibrillation without prior arrhythmia history. Follow-up visits will occur periodically to monitor the occurrence of bleeding events, defined by a score ≥2 on the BARC scale, and other secondary endpoints such as MACCE and ischemic events. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 12 months, depending on individual treatment response and safety outcomes.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial will utilize two oral anticoagulants, **rivaroxaban** and **warfarin sodium**, administered in the form of film-coated tablets and tablets, respectively. The maximum daily dose for rivaroxaban is 20 mg, while for warfarin sodium, it is 5 mg. The study aims to provide insights into the management of anticoagulant therapy in this patient population, with a focus on minimizing hemorrhagic events.

The clinical trial involves the administration of **Xarelto**, a pharmaceutical product containing the active substance **rivaroxaban**. Xarelto is provided in the form of film-coated tablets, each containing 10 mg of the active ingredient. The medication is administered orally, with a maximum daily dose of 20 mg. The treatment period for Xarelto is set to a maximum of 12 months. The product is manufactured by Bayer AG and is classified under the ATC code B01AF01. The chemical origin of rivaroxaban ensures its role as a direct oral anticoagulant, utilized in the management of anticoagulant therapy in patients with acute coronary syndrome and de novo atrial fibrillation arrhythmia.

In addition to Xarelto, the trial also includes the administration of **Coumadine**, which contains the active substance **warfarin sodium**. Coumadine is available as a tablet, specifically a scored tablet, with each unit containing 5 mg of warfarin sodium. This medication is also administered orally, with a maximum daily dose of 5 mg. The treatment duration for Coumadine is similarly capped at 12 months. Manufactured by Teofarma S.R.L., Coumadine is categorized under the ATC code B01AA03. Warfarin sodium, of chemical origin, functions as a vitamin K antagonist, serving as a comparator treatment in the study to evaluate the safety and efficacy of anticoagulant therapy monitored by an implantable device with telecardiology.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to assess the safety of anticoagulant treatment strategies in terms of hemorrhagic event occurrence, comparing the systematic introduction of anticoagulant treatment based on the CHA2DS2-VASc score with a treatment approach guided by data from an implantable Holter device with remote monitoring.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the occurrence of a bleeding event during the two-year follow-up period, defined by a score of ≥2 according to the BARC scale. Secondary endpoints include the occurrence of events defined by the MACCE indicator and ischemic events, which are characterized by a composite indicator encompassing death from cardiovascular causes, stroke or systemic embolism, non-fatal infarction, and the need for revascularization.

The trial aims to evaluate the safety of anticoagulant treatment in patients with Acute Coronary Syndrome (ACS) and de novo **Atrial Fibrillation** (AF) using data from an implantable Holter device with remote monitoring. The efficacy parameters will be collected and analyzed over a two-year period, with specific attention to the occurrence of hemorrhagic and ischemic events. The BARC scale will be utilized as a tool for assessing bleeding events, ensuring a standardized approach to measuring and analyzing the primary endpoint.