Evaluation of Escalated Prasugrel or Ticagrelor with Direct Oral Anticoagulation in Atrial Fibrillation and Acute Coronary Syndrome Undergoing PCI

The primary objective of the study is to evaluate whether an **escalated antiplatelet therapy** using a potent P2Y12-inhibitor, such as Prasugrel or Ticagrelor, for a duration of four weeks can effectively reduce ischaemic events without significantly increasing bleeding complications in patients diagnosed with atrial fibrillation and either ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI), who are undergoing percutaneous coronary intervention (PCI). This is clinically relevant as it aims to optimize treatment strategies for reducing cardiovascular events while minimizing the risk of bleeding in this high-risk patient population.

Secondary objectives include investigating the effect of platelet function, as assessed by platelet function testing (PFT), on ischaemic and bleeding complications within a predefined substudy. This will provide further insights into the relationship between platelet activity and clinical outcomes, potentially guiding personalized therapeutic approaches.

The clinical trial involves **patients with atrial fibrillation** and either ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI), specifically those undergoing percutaneous coronary intervention (PCI). The study population includes both male and female participants aged 18 years and older. Participants are required to have atrial fibrillation necessitating oral anticoagulation and must have successfully completed PCI, defined as achieving a TIMI flow grade of 2 or more. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Key lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The selection criteria emphasize the need for written informed consent and the presence of biomarker-positive acute coronary syndrome. The trial aims to evaluate the efficacy of escalated antiplatelet therapy with potent P2Y12-inhibitors over a four-week period, focusing on reducing ischemic events without significantly increasing bleeding complications.

The clinical trial is designed to evaluate the efficacy and safety of escalated antiplatelet therapy using potent **P2Y12-inhibitors** such as **Prasugrel** or **Ticagrelor** in patients with atrial fibrillation and acute coronary syndrome undergoing percutaneous coronary intervention (PCI). This is a randomized, double-blind, controlled trial with an estimated duration extending until June 2026. The trial aims to determine if a 4-week regimen of these inhibitors can reduce ischemic events without significantly increasing bleeding complications. Participants will be randomly assigned to receive either the test or comparator drugs, with **Acetylsalicylic Acid** and **Clopidogrel** serving as comparators.

The study involves several key visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as age (≥18 years), atrial fibrillation requiring oral anticoagulation, and successful completion of PCI. Randomization occurs within 5 days post-PCI, preferably within 24 hours. Follow-up visits are scheduled to monitor the primary efficacy endpoint, which includes major ischemic events, and the primary safety endpoint, focusing on bleeding events as per the Bleeding Academic Research Consortium (BARC) criteria. These endpoints are assessed at 6 weeks post-randomization. Secondary endpoints, such as cardiovascular mortality and unplanned hospitalizations, are evaluated at both 6 weeks and 6 months.

Participant involvement is expected to last up to 6 months, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial's design ensures rigorous monitoring and data collection to achieve its objectives, contributing valuable insights into the management of patients with atrial fibrillation and acute coronary syndrome.

The clinical trial involves the administration of several medications, each with specific roles and characteristics. **Acetylsalicylic acid** is utilized in the form of a gastro-resistant tablet. The active substance, acetylsalicylic acid, is chemically derived and functions by inhibiting platelet aggregation. The maximum daily dose is 100 mg, administered orally, with a treatment period not exceeding 7 days. This medication serves as a comparator in the trial.

**Ticagrelor** is provided as a film-coated tablet, with the active substance being ticagrelor, also chemically derived. It acts as a P2Y12 ADP receptor antagonist, inhibiting platelet activity and aggregation. The maximum daily dose is 90 mg, administered orally, with a treatment period of up to 4 weeks. Ticagrelor is a test medication in this study.

**Clopidogrel** is administered in the form of a film-coated tablet. The active substance, clopidogrel, is a chemical prodrug, with one of its metabolites inhibiting platelet aggregation. The maximum daily dose is 75 mg, taken orally, with a treatment duration of up to 6 weeks. Clopidogrel is also a comparator in the trial.

**Prasugrel** is available as a film-coated tablet, with the active substance prasugrel being chemically derived. It inhibits platelet activity and aggregation. The maximum daily dose is 10 mg, administered orally, with a treatment period of up to 4 weeks. Prasugrel is used as a test medication in the study.

All medications are administered orally, and participant compliance is monitored throughout the trial. The study aims to evaluate the efficacy of escalated antiplatelet therapy in reducing ischemic events without significantly increasing bleeding complications in patients with atrial fibrillation and acute coronary syndrome undergoing percutaneous coronary intervention.

The efficacy of the clinical trial will be assessed through a series of predefined endpoints. The primary efficacy endpoint is the occurrence of major **ischaemic events**, which is defined as a composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis, ischaemic stroke, or systemic thromboembolism. This will be evaluated at 6 weeks after randomization using a superiority test. Secondary endpoints include the individual components of the primary endpoint, cardiovascular mortality, and urgent revascularization, all assessed at 6 weeks post-randomization. Additionally, all-cause mortality, unplanned hospitalization due to acute heart failure or acute coronary syndrome, and ischaemic stroke will be evaluated at 6 months after randomization.

The efficacy parameters will be measured and collected at specified timepoints, namely 6 weeks and 6 months after randomization. The analysis will involve comparing the incidence of these events between the treatment groups. The trial aims to determine if an escalated antiplatelet therapy with a potent P2Y12-inhibitor, such as Prasugrel or Ticagrelor, for 4 weeks can effectively reduce ischaemic events without significantly increasing bleeding complications in patients with atrial fibrillation and acute coronary syndrome undergoing percutaneous coronary intervention.