Evaluation of Single Versus Dual Antiplatelet Therapy with Clopidogrel and Acetylsalicylic Acid in Elderly or High Bleeding Risk Patients Post-PCI with Drug-Coated Balloons

The primary objective of this study is to assess the **non-inferiority** of single antiplatelet therapy (SAPT) compared to dual antiplatelet therapy (DAPT) in terms of major adverse cardiac events (MACE), which include all-cause mortality, target vessel revascularization (TVR), and target vessel spontaneous myocardial infarction (MI) at 12 months following successful drug-coated balloon (DCB) angioplasty. This is clinically relevant as it may influence treatment strategies for elderly or high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI), potentially reducing the risk of bleeding while maintaining efficacy.

Secondary objectives include evaluating: - Procedural success, defined as correct delivery of the device with final stenosis <30%, distal TIMI 3 flow, and absence of in-hospital major adverse events. - The occurrence of cardiac death. - The occurrence of death from any cause. - The occurrence of Q-wave myocardial infarction (MI). - The occurrence of any MI, including periprocedural MI, diagnosed according to the Fourth Definition of MI. - The occurrence of target lesion revascularization (TLR). - The occurrence of target vessel revascularization. - The occurrence of any bleeding following the BARC classification. - The occurrence of transfusion rates. - The rate of clinically relevant bleeding events (Bleeding Academic Research Consortium 2, 3, or 5) at 12 months.

The clinical trial involves **patients with stable or unstable coronary syndromes** who have undergone successful percutaneous coronary intervention (PCI). The study population includes both male and female participants, aged 75 years or older, or those identified as being at high bleeding risk. The trial does not involve a vulnerable population. Participants were selected based on their recent successful PCI with Essential Pro drug-coated balloon (DCB) angioplasty performed on one, two, or three coronary vessels, with de novo coronary lesions in vessels measuring between 2.0 and 4.0 mm in diameter. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. Informed consent was obtained from all participants or an impartial witness. The trial aims to assess the non-inferiority of single antiplatelet therapy (SAPT) compared to dual antiplatelet therapy (DAPT) in terms of major adverse cardiac events (MACE) at 12 months following successful DCB angioplasty.

The clinical trial is designed to evaluate the non-inferiority of **single antiplatelet therapy (SAPT)** compared to dual antiplatelet therapy (DAPT) in patients with stable or unstable coronary syndromes who have undergone successful percutaneous coronary intervention (PCI) with drug-coated balloons. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The study is expected to span a total duration of approximately 30 months, with recruitment anticipated to commence on July 1, 2025, and the estimated end date set for December 31, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as successful PCI, de novo coronary lesions, and age or bleeding risk factors. Following the screening, participants will be randomly assigned to receive either SAPT or DAPT. The trial will include follow-up visits at 1 month, 6 months, and 12 months to monitor the primary endpoint of major adverse cardiac events (MACE) and secondary endpoints such as procedural success, patient-oriented composite endpoints, and quality of life assessments using the EQ-5D-5L questionnaire. The end-of-study visit will occur at 12 months post-intervention to evaluate the long-term outcomes and safety of the treatment regimens.

Participant involvement is expected to last for 12 months, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The trial will utilize **clopidogrel** and **acetylsalicylic acid** as the investigational products, administered orally in the form of film-coated and gastro-resistant tablets, respectively. The maximum daily doses are set at 75 mg for clopidogrel and 100 mg for acetylsalicylic acid, with a treatment period not exceeding 12 months. The study aims to provide critical insights into the efficacy and safety of antiplatelet therapies in a high-risk patient population, contributing to optimized clinical management strategies.

The clinical trial involves the administration of **Clopidogrel**, an anti-platelet medication, in the form of film-coated tablets. The active substance, clopidogrel, is of chemical origin. The maximum daily dose is 75 mg, administered orally. The treatment period extends up to 12 months. Clopidogrel is utilized as both a test and comparator treatment in the study, depending on the specific trial arm. Participant compliance with the dosing regimen is monitored throughout the trial duration.

**Acetylsalicylic Acid** is also employed in the trial as an anti-platelet agent. It is provided in the form of gastro-resistant tablets, with a maximum daily dose of 100 mg, administered orally. The treatment period for acetylsalicylic acid is similarly up to 12 months. This medication serves as both a test and comparator treatment in different arms of the study. Compliance with the dosing schedule is carefully monitored to ensure adherence to the trial protocol.

Both medications are administered orally, and the trial aims to evaluate the efficacy of single versus dual antiplatelet therapy in elderly or high bleeding risk patients undergoing percutaneous intervention with drug-coated balloons. The primary objective is to assess the non-inferiority of single antiplatelet therapy compared to dual antiplatelet therapy in terms of major adverse cardiac events over a 12-month period following successful drug-coated balloon angioplasty.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the occurrence of Major Adverse Cardiac Events (**MACE**) at 12 months, which includes all-cause mortality, target vessel revascularization (TVR), and target vessel spontaneous myocardial infarction (MI). The trial aims to verify the non-inferiority of Single Antiplatelet Therapy (SAPT) compared to Dual Antiplatelet Therapy (DAPT) in terms of MACE following successful drug-coated balloon angioplasty.

Secondary endpoints include procedural success, defined as final stenosis of less than 30%, distal TIMI 3 flow, and absence of in-hospital major adverse events, with an expected success rate of 95%. Additional secondary endpoints are the patient-oriented composite endpoint (PoCE), cardiovascular and cardiac death, all-cause death, Q-wave MI, any MI, target lesion revascularization (TLR), TVR, acute vessel occlusion according to ARC criteria, transfusion rates, and bleeding events classified as BARC 2, 3, or 5. Functional status and quality of life (QoL) will be assessed using the EQ-5D-5L questionnaire at baseline, 1 month, 6 months, and 12 months, with changes in scores indicating improvement, deterioration, or no change.