Assessment of Ticagrelor-Based De-Escalation Antiplatelet Strategies Versus Standard Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients

The primary objective of this study is to assess and compare the clinical **safety** of two ticagrelor-based antiplatelet de-escalation strategies with standard dual antiplatelet therapy (DAPT) in patients with **Acute Coronary Syndrome (ACS)**. This evaluation is clinically relevant as it aims to determine safer therapeutic options for managing ACS, potentially reducing adverse events associated with standard DAPT.

The secondary objective is to compare the clinical efficacy of the two ticagrelor-based antiplatelet de-escalation strategies with standard DAPT. This comparison is crucial for understanding the effectiveness of alternative treatment strategies in achieving desired clinical outcomes in ACS management.

The clinical trial involves participants diagnosed with **Acute Coronary Syndrome (ACS)**, including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), or unstable angina (UA). The study population comprises both male and female subjects aged 18 years and older. Participants are required to have a general health status that allows them to understand and comply with the study protocol. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include the ability to provide informed consent and a diagnosis of ACS as per established medical guidelines. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the safety and efficacy of two ticagrelor-based de-escalation antiplatelet strategies in patients with **acute coronary syndrome** (ACS). This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to last until June 2026, with participant recruitment having commenced in September 2021. The trial involves a series of study visits, beginning with an inclusion visit where participants are screened for eligibility based on criteria such as age, diagnosis of ACS, and ability to comply with the study protocol. Follow-up visits are scheduled to monitor the participants' health and adherence to the treatment regimen, with the primary endpoint being the first occurrence of type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) criteria within 12 months. Secondary endpoints include various bleeding events, death from any cause, myocardial infarction, and other cardiovascular events. The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted. Participants are expected to be involved for a maximum of 12 months, with conditions for early termination including non-compliance with the study protocol or withdrawal of consent. The trial involves the administration of **acetylsalicylic acid** and **ticagrelor**, both orally, with the maximum treatment period set at 12 months. The study aims to provide valuable insights into the comparative safety of these antiplatelet strategies in managing ACS.

The clinical trial involves the administration of **ASPIRIN CARDIO**, a **gastro-resistant tablet** containing **acetylsalicylic acid** as the active substance. This medication is provided in a dosage of 100 mg per tablet and is administered orally. The maximum daily dose is 100 mg, and the treatment period extends up to 12 weeks. The tablets are packaged in blisters labeled with an opaque film, allowing for easy extraction of the tablet. This medication is classified as a non-steroidal anti-inflammatory agent and is produced by Bayer Sp. z o.o.

Another experimental treatment in the trial is **Brilique**, available in two formulations: 60 mg film-coated tablets and 90 mg orodispersible tablets, both containing **ticagrelor** as the active ingredient. The 60 mg film-coated tablets are administered orally with a maximum daily dose of 120 mg, while the 90 mg orodispersible tablets have a maximum daily dose of 180 mg. Both formulations are designed for a treatment period of up to 12 weeks. The tablets are packaged similarly to the aspirin tablets, with blisters labeled for easy extraction. Ticagrelor is an oral antiplatelet drug, and both formulations are manufactured by AstraZeneca AB.

The trial also includes a **placebo** component, consisting of microcrystalline cellulose and corn starch, with a coating made from a copolymer of methacrylic acid and methyl acrylate, polysorbate 80, sodium lauryl sulfate, talc, and triethyl citrate. This placebo is used to ensure the double-blind nature of the study, allowing for unbiased comparison of the experimental treatments' efficacy and safety.

Efficacy in the clinical trial will be assessed through a series of predefined primary and secondary endpoints. The primary endpoint is the first occurrence of type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) criteria within 12 months of observation, analyzed using a time-to-event approach. BARC type 2 bleeding involves any clinically overt sign of hemorrhage that necessitates diagnostic studies, hospitalization, or treatment by a healthcare professional. BARC type 3 bleeding includes overt bleeding with a hemoglobin drop of 3 to less than 5 g/dL, transfusion with overt bleeding, or more severe conditions such as cardiac tamponade or intracranial hemorrhage. BARC type 5 bleeding is defined as fatal bleeding.

Secondary endpoints include BARC type 3 or 5 bleeding, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate, severe, or life-threatening bleeding, and International Society of Thrombosis and Haemostasis (ISTH) major bleeding. Additional secondary endpoints encompass death from any cause, death from cardiovascular causes, myocardial infarction, ischemic stroke, definite or probable stent thrombosis, adherence to study treatment, and dyspnea. These endpoints will be measured and analyzed at specified intervals throughout the trial duration to evaluate the efficacy of the ticagrelor-based antiplatelet de-escalation strategies compared to standard dual antiplatelet therapy in patients with acute coronary syndrome.