Evaluation of Short Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy in Elderly Patients Post-Percutaneous Coronary Intervention

The primary objective of this study is to evaluate whether a short duration of **dual antiplatelet therapy** (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 inhibitor is non-inferior to standard DAPT in terms of net clinical benefit. This composite endpoint includes all-cause death, myocardial infarction, stroke, and major bleeding (BARC 3 or 5) at one year in elderly patients undergoing percutaneous coronary intervention (PCI). This is clinically relevant as it aims to optimize antiplatelet therapy duration, potentially reducing bleeding risks while maintaining efficacy in preventing ischemic events in this vulnerable population.

Secondary objectives include:

• Determining whether short DAPT is non-inferior or superior to standard DAPT regarding major or clinically relevant non-major bleeding (BARC 2, 3, or 5).
• Assessing if short DAPT is non-inferior to standard DAPT concerning an ischemic composite endpoint, including all-cause death, myocardial infarction, and stroke.
• Evaluating if short DAPT is superior to standard DAPT regarding major bleeding (BARC 3 or 5) and net clinical benefit.
• Comparing the rates of individual components of the ischemic composite endpoint between the two strategies.
• Comparing the rates of cardiovascular death, stent thrombosis, intracranial bleeding, all-cause hospitalizations, and urgent/unplanned symptoms-driven coronary revascularization between the two strategies.

The clinical trial involves a study population of **elderly patients** aged 65 years and older who have been successfully treated with percutaneous coronary intervention (PCI) using at least one drug-eluting stent for either acute or chronic coronary syndrome. The trial includes both male and female participants, and the population is not considered vulnerable. The sponsor has not provided the total number of participants. Participants were selected based on their successful treatment with PCI, and randomization occurs before discharge from the study site. Key lifestyle considerations such as diet, physical activity, or habits are not specified. The trial does not focus on a vulnerable population, and the inclusion criteria emphasize the age and specific medical treatment received. The sponsor has not disclosed additional information regarding the selection process or lifestyle factors.

The clinical trial is designed to evaluate the **safety** and efficacy of a very short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 inhibitor in elderly patients undergoing percutaneous coronary intervention (PCI). The trial is structured as a randomized, double-blind, controlled study, aiming to determine the non-inferiority of the short DAPT followed by SAPT compared to standard DAPT in terms of net clinical benefit, which includes a composite of all-cause death, myocardial infarction, stroke, and major bleeding (BARC 3 or 5) at one year. The trial is expected to commence recruitment on January 1, 2025, and conclude by January 1, 2029.

Participants will be involved in the study for a maximum of 12 months. The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as age (≥ 65 years), successful PCI with at least one drug-eluting stent, and informed consent. Randomization will occur before discharge from the study site. Follow-up visits will be scheduled periodically to monitor the participants' health status and adherence to the treatment protocol. The end-of-study visit will assess the primary and secondary endpoints, including major cardiovascular and cerebrovascular events, bleeding events, and overall clinical outcomes.

Participants may be withdrawn from the study early if they experience adverse events that compromise their safety, fail to adhere to the study protocol, or withdraw consent. The trial will utilize oral administration of the investigational products, including **ticagrelor**, **clopidogrel**, and **prasugrel**, with the maximum treatment period for each product being 12 months. The study aims to provide valuable insights into optimizing antiplatelet therapy in elderly patients post-PCI, with a focus on balancing efficacy and safety.

The clinical trial involves the administration of **KARDEGIC 75 mg**, a powder for oral solution in sachet-dose form. The active substance in this medication is **D,L-LYSINE ACETYLSALICYLATE**, a chemical compound. The maximum daily dose is 100 mg, administered orally, with a treatment period not exceeding 7 days. This medication is produced by Sanofi Winthrop Industrie and is not a pediatric formulation. The pharmaceutical form is classified as an oral solution, and the medication is used as an auxiliary treatment in the trial.

**Brilique 90 mg** film-coated tablets are also utilized in the trial. The active ingredient is **TICAGRELOR**, a chemical substance. The maximum daily dose is 180 mg, administered orally, with a treatment period of up to 12 months. Manufactured by AstraZeneca AB, this medication is not intended for pediatric use. The tablets serve as an auxiliary treatment in the study, and the pharmaceutical form is a film-coated tablet.

Another treatment used in the trial is **Plavix 75 mg** film-coated tablets, containing the active substance **CLOPIDOGREL**, a chemical compound. The maximum daily dose is 75 mg, administered orally, with a treatment period of up to 12 months. Produced by Sanofi Winthrop Industrie, this medication is not a pediatric formulation and is used as an auxiliary treatment. The pharmaceutical form is a film-coated tablet.

Lastly, **Efient 10 mg** film-coated tablets are included in the trial. The active substance is **PRASUGREL**, a chemical compound. The maximum daily dose is 10 mg, administered orally, with a treatment period of up to 12 months. This medication is manufactured by Vygoris Limited and is not intended for pediatric use. It is used as a test treatment in the study, and the pharmaceutical form is a film-coated tablet.

The efficacy of the clinical trial will be assessed by evaluating the **net clinical benefit**, which is a composite endpoint consisting of all-cause death, myocardial infarction, stroke, and major bleeding defined as BARC (Bleeding Academic Research Consortium) grade 3 or 5. The primary endpoint is to determine the non-inferiority of short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 inhibitor compared to standard DAPT at 1 year in elderly patients undergoing percutaneous coronary intervention (PCI).

Secondary endpoints include the evaluation of major or clinically relevant non-major bleeding (BARC 2, 3, or 5) for non-inferiority, net clinical benefit evaluated as superior or not, all-cause death, myocardial infarction types 1, 3, or 4b, any stroke, intracranial bleeding defined by NeuroARC, cardiovascular death, stent thrombosis, all-cause hospitalization, and urgent or unplanned symptoms-driven coronary revascularization. The study will also assess major cardiovascular and cerebrovascular events and major bleeding for superiority.