Comparison of Drug-Coated Balloon and Drug-Eluting Stents in High Bleeding Risk Patients with Coronary Artery Disease: A Study of Prasugrel, Acetylsalicylic Acid, and Ticagrelor

The primary objective of the study is to evaluate the efficacy of **percutaneous coronary intervention** (PCI) using a **drug-coated balloon** (DCB) compared to **drug-eluting stents** (DES) in patients with stable **coronary artery disease** (CAD) or acute coronary syndromes (ACS) who are at high risk of bleeding. The study hypothesizes that the DCB strategy, combined with a shorter duration of dual-antiplatelet therapy (DAPT), is non-inferior to the DES strategy, which involves a longer DAPT duration. This comparison is clinically relevant as it may offer a safer alternative for patients at high bleeding risk, potentially reducing the duration of antiplatelet therapy and associated complications.

Secondary objectives include testing the superiority of the DCB strategy over the DES strategy if non-inferiority is demonstrated. This aspect of the study aims to further establish the potential benefits of the DCB approach in terms of clinical outcomes and patient safety.

The clinical trial involves participants diagnosed with **coronary artery disease** or acute coronary syndromes, focusing on individuals at high risk of bleeding. The study population includes both male and female subjects aged 18 years and older. Participants are required to provide informed written consent and meet specific bleeding risk criteria as defined by the Academic Research Consortium. The trial does not include vulnerable populations. The sponsor has not provided the total number of participants. The selection criteria emphasize the presence of stable angina or dyspnea with coronary narrowing, or acute coronary syndromes with specific electrocardiographic changes and troponin levels. Participants must have at least one de novo lesion in native coronary arteries or bypass vein grafts, with a reference vessel diameter between 2.0 and 5.0 mm and lesion length of 40 mm or less, suitable for percutaneous coronary intervention. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of percutaneous coronary intervention using a drug-coated balloon (DCB) compared to drug-eluting stents (DES) in patients with **coronary artery disease** who are at high risk of bleeding. 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 run until December 31, 2027, with recruitment starting on November 1, 2023. Participants will be involved in the study for a maximum treatment period of 12 months, with the primary endpoint being the composite of Major Adverse Cardiac Events (MACE) and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding episodes at 12 months.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age (≥18 years), written informed consent, and specific bleeding risk factors. Following the initial visit, participants will undergo follow-up visits at 12, 24, and 36 months to assess secondary endpoints, including MACE, BARC bleedings, total mortality, and other cardiovascular outcomes. The end-of-study visit will occur at the conclusion of the participant's involvement, ensuring comprehensive data collection and safety monitoring.

Participant involvement is expected to last up to 36 months, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The trial will utilize oral administration of antithrombotic drugs such as **prasugrel**, **acetylsalicylic acid**, **ticagrelor**, and **clopidogrel**, which have been in clinical use for years, ensuring a low-intervention approach. The study aims to provide valuable insights into optimizing treatment strategies for patients with high bleeding risk undergoing coronary interventions.

The clinical trial involves the administration of several **experimental medications**. The first medication is Efient, which contains the active substance **prasugrel**. It is provided in the form of film-coated tablets, with each tablet containing 10 mg of prasugrel. The medication is administered orally, with a maximum daily dose of 60 mg. The treatment period for Efient is up to 12 months. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

Another medication used in the trial is ASPIRIN CARDIO, which contains **acetylsalicylic acid** as its active ingredient. This medication is available as gastro-resistant tablets, each containing 100 mg of acetylsalicylic acid. The oral administration of ASPIRIN CARDIO allows for a maximum daily dose of 500 mg. The treatment duration can extend up to 999 months, and participant compliance is closely monitored to maintain the integrity of the study.

Brilique, containing the active substance **ticagrelor**, is also part of the trial. It is supplied as film-coated tablets, with each tablet containing 90 mg of ticagrelor. The medication is administered orally, with a maximum daily dose of 180 mg. The treatment period for Brilique is up to 12 months, and adherence to the dosing schedule is ensured through regular compliance checks.

Additionally, Plavix, which contains **clopidogrel** as its active substance, is included in the study. It is available in the form of film-coated tablets, with each tablet containing 75 mg of clopidogrel. The oral administration of Plavix allows for a maximum daily dose of 600 mg. The treatment duration is up to 12 months, and participant compliance is monitored to ensure adherence to the prescribed dosing regimen.

All medications in the trial are administered orally, and the study design includes rigorous monitoring of participant compliance to ensure accurate and reliable results. The trial aims to evaluate the efficacy and safety of these medications in patients with stable coronary artery disease or acute coronary syndromes who are at high risk of bleeding.

Efficacy in the clinical trial titled "Drug-Coated Balloon in Anticoagulated and Bleeding Risk Patients Undergoing PCI (DEBATE)" will be assessed using a combination of primary and secondary endpoints. The primary endpoint is the composite of Major Adverse Cardiac Events (MACE) and BARC (Bleeding Academic Research Consortium) type 2-5 bleeding episodes at 12 months. MACE is defined as a composite of cardiac death, nonfatal **myocardial infarction** (MI), and ischemia-driven target lesion revascularization (ID-TLR).

Secondary endpoints include a variety of measures assessed at 12, 24, and 36 months. These include the composite of MACE and BARC2-5 bleedings, MACE alone, BARC2-5 and BARC3-5 bleedings, total mortality, cardiovascular mortality, myocardial infarction, target lesion revascularization (TLR), target-vessel failure (TVF), and target-lesion failure (TLF). Additional secondary endpoints involve the composite of TLR and BARC2-5 bleedings, TVF and BARC2-5 bleedings, TLF and BARC2-5 bleedings, TLR and BARC3-5 bleedings, acute vessel closure as defined by consensus criteria for definite/probable stent thrombosis, hospitalization for urgent revascularization, and stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA).