Evaluation of Low-Dose Acetylsalicylic Acid Plus Prasugrel Versus Low- and High-Dose Acetylsalicylic Acid on Graft Patency in Stable Coronary Artery Disease Post-CABG

The primary objective of this study is to compare the effect of low-dose **acetylsalicylic acid** (ASA) plus **prasugrel** with low-dose ASA and with high-dose ASA for 3 months, followed by low-dose ASA alone, on graft failure in patients with stable coronary artery disease undergoing randomization following coronary artery bypass grafting (CABG) procedure. This is clinically relevant as it aims to determine the optimal antiplatelet therapy to prevent graft failure, a significant complication that can impact patient outcomes post-CABG.

Secondary objectives include:

• Investigating the effect of low-dose ASA plus prasugrel versus low-dose ASA and versus high-dose ASA, and low-dose ASA versus high-dose ASA on the 12-month risk of ischemic and bleeding events, and assessing quality of life at 6, 12 months, and long-term after randomization following CABG procedure.
• Evaluating the safety of low-dose ASA plus prasugrel versus low-dose ASA and versus high-dose ASA 12 weeks after randomization following CABG procedure.
• Comparing the effect of low-dose ASA with high-dose ASA for 3 months followed by low-dose ASA alone on graft failure in patients with stable coronary artery disease undergoing randomization following CABG procedure.

The clinical trial involves **participants** diagnosed with stable coronary artery disease, specifically those undergoing primary isolated coronary artery bypass grafting (CABG) and planned for at least two grafts. The study population includes both male and female subjects over the age of 18, with no vulnerable populations selected. Participants are required to have a stenosis of 70% or greater, as determined by coronary angiography, or equivalent measurements. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants must be able to comply with all study and follow-up procedures and have signed informed consent. Lifestyle considerations such as diet and physical activity are not detailed in the available data. Key inclusion criteria include intraoperative graft evaluation using transit time flow measurement, with specific flow and pulsatility index requirements, and the grafting of the left anterior descending artery with the internal thoracic artery. Exclusion criteria include any intraoperative decision for hybrid revascularization, endarterectomy of the grafted vessel, or any additional unplanned procedures.

The clinical trial is designed to evaluate the efficacy and safety of different **antiplatelet** therapy regimens in patients with stable **coronary artery disease** undergoing coronary artery bypass grafting (CABG). The trial employs a randomized, double-blind, controlled design to ensure unbiased results. Participants will be randomly assigned to one of three groups: low-dose acetylsalicylic acid (ASA) plus prasugrel, low-dose ASA alone, or high-dose ASA. The primary objective is to assess the proportion of failed grafts 12 months post-randomization, using the Fitzgibbon classification. Secondary endpoints include safety assessments, incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and quality of life evaluations.

The trial is expected to commence recruitment on October 1, 2025, and conclude by April 30, 2029. Participant involvement will span approximately 12 months, with the treatment phase lasting 3 months, followed by a 9-month follow-up period. Study visits are structured as follows: an initial screening visit to confirm eligibility, randomization, and baseline assessments; subsequent visits at 6 weeks, 3 months, 6 months, and 12 months post-randomization to monitor treatment adherence, collect safety data, and perform efficacy evaluations. The end-of-study visit at 12 months will include a comprehensive assessment of all endpoints.

Inclusion criteria require participants to be over 18 years of age, with a diagnosis of stable coronary artery disease and planned for at least two grafts. Exclusion criteria are not specified in the provided data. Participants may be withdrawn from the study if they are unable to comply with study procedures, experience significant adverse events, or if the investigator deems it necessary for safety reasons. The trial will adhere to ethical standards, with informed consent obtained from all participants prior to enrollment.

The clinical trial involves the administration of **acetylsalicylic acid** in two different dosages. The first formulation is a **gastro-resistant tablet** containing **acetylsalicylic acid** as the active substance. This formulation is administered orally with a maximum daily dose of 300 mg. The treatment period for this dosage is set for a maximum of three months. The **acetylsalicylic acid** used in this trial is a synthetic non-steroidal anti-inflammatory drug, and it is not a paediatric formulation. The compliance of participants with the dosing schedule will be monitored throughout the trial.

The second formulation of **acetylsalicylic acid** is also a **gastro-resistant tablet**, but with a lower dosage. This formulation is administered orally with a maximum daily dose of 75 mg. Similar to the higher dose, the treatment period is limited to three months. This formulation is also a synthetic non-steroidal anti-inflammatory drug and is not intended for paediatric use. Participant adherence to the dosing regimen will be closely monitored to ensure compliance.

Additionally, the trial includes the administration of **prasugrel**, a **film-coated tablet** containing **prasugrel** as the active substance. This medication is administered orally with a maximum daily dose of 10 mg. The treatment duration for **prasugrel** is also set for a maximum of three months. **Prasugrel** is classified as a synthetic antiplatelet agent and is not formulated for paediatric use. Monitoring of participant compliance with the dosing schedule is an integral part of the trial protocol.

Efficacy in the clinical trial titled "Comparing high and lOw-dose asPirin with dual anTIplatelet therapy for three Months using prasUgrel and aSpirin following Coronary Artery Bypass Grafting (OPTIMUS-CABG trial)" will be assessed through several primary and secondary endpoints. The primary endpoint involves the assessment of the proportion of failed grafts, defined according to the Fitzgibbon classification (Fitzgibbon Class B + O), 12 months after randomization following the Coronary Artery Bypass Grafting (CABG) procedure. This will be evaluated in patients receiving dual antiplatelet therapy (DAPT) with prasugrel (10 mg/day) plus **acetylsalicylic acid** (ASA) (75 mg/day) versus high-dose ASA (300 mg/day) and DAPT versus low-dose ASA (75 mg/day).

Secondary endpoints include the assessment of the proportion of failed grafts, also defined by the Fitzgibbon classification, in patients receiving high-dose versus low-dose ASA. Additional secondary endpoints encompass safety and efficacy assessments based on the frequency of reported adverse events during the first 6 and 12 months and long-term follow-up after randomization. These include all-cause mortality, incidence of myocardial infarction, stroke, repeat revascularization, and major adverse cardiac and cerebrovascular events (MACCE) at 12 months and beyond. The safety of treatment will be evaluated in terms of the incidence of bleeding within 12 months according to the Bleeding Academic Research Consortium (BARC) type 2, 3, or 5. Quality of life will be assessed using the SAQ 7 and SF 12 questionnaires. The safety of short-term use of the investigational product will be assessed until 12 weeks from the randomization visit based on the frequency of reported adverse events, including type, grading, and relationship to prasugrel/ASA.