Evaluation of CYP2C19-Genotype-Guided P2Y12 Inhibitor Selection with Ticagrelor and Clopidogrel in Patients with Coronary Artery Disease Undergoing PCI

The primary objective of the COATS study is to evaluate the **feasibility** and **safety** of CYP2C19-genotype-guided P2Y12 inhibitor selection in patients with coronary artery disease who are indicated for direct oral anticoagulants (D)OAC and require percutaneous coronary intervention (PCI). This objective is clinically relevant as it aims to optimize antithrombotic therapy, potentially improving patient outcomes by tailoring treatment based on genetic testing, thereby reducing the risk of adverse events and enhancing therapeutic efficacy.

Secondary objectives include:

• Safety evaluation in study subgroups, which is crucial for understanding the differential impact of the intervention across diverse patient populations.
• Efficacy evaluation in study subgroups, providing insights into the effectiveness of the genotype-guided approach in various demographic and clinical settings.
• Improvement in quality of life, assessed by the EQ5D5L questionnaire, both prior to and following PCI, which is important for evaluating the broader impact of the intervention on patient well-being.

The clinical trial involves **patients with coronary artery disease** who have an indication for percutaneous coronary intervention (PCI). The study population includes both male and female participants aged 18 years and older. Participants are required to have an indication for indefinite direct oral anticoagulant (D)OAC therapy and must have undergone successful PCI for either stable or unstable acute coronary syndrome (ACS). All participants have provided written informed consent as approved by the ethics committee. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the feasibility and safety of **CYP2C19-genotype**-guided P2Y12 inhibitor selection in patients with coronary artery disease who are indicated for direct oral anticoagulants (DOAC) and require percutaneous coronary intervention (PCI). The study employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The trial is expected to span a duration of 12 months, with the estimated recruitment start date being April 19, 2023, and the anticipated end date on May 2, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), indication for indefinite DOAC, successful PCI for stable or unstable coronary artery disease, and provision of written informed consent. Following the screening, participants will be randomly assigned to receive either **ticagrelor** or **clopidogrel** as part of their antithrombotic regimen. The trial will include regular follow-up visits to monitor safety and efficacy outcomes, with primary endpoints focusing on major and clinically relevant non-major (CRNM) bleeding, as well as a composite of all-cause mortality, myocardial infarction, stroke, and stent thrombosis at 12 months.

The expected length of participant involvement is 12 months, during which safety and efficacy will be assessed through both primary and secondary endpoints. Secondary endpoints include subgroup analyses comparing major and CRNM bleeding, as well as efficacy outcomes between different study groups (ACS/ticagrelor vs. ACS/clopidogrel vs. elective/ticagrelor vs. elective/clopidogrel). The EQ5D5L questionnaire will also be utilized to evaluate health state profiles across these groups. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or any other medical reasons deemed necessary by the investigator.

The clinical trial involves the administration of **Brilique** 90 mg film-coated tablets, which contain the active substance **ticagrelor**. Ticagrelor is a chemical compound used as an antiplatelet medication. The pharmaceutical form of Brilique is a film-coated tablet, and it is administered orally. The dosage regimen for Brilique in this study is 90 mg taken twice daily, resulting in a maximum daily dose of 180 mg. The treatment period for participants receiving Brilique is up to 12 months. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

The comparator treatment in this trial is **Clopidogrel Medreg** 75 mg film-coated tablets, containing the active substance **clopidogrel**. Clopidogrel is also a chemical compound and functions as an antiplatelet agent. The pharmaceutical form is a film-coated tablet, administered orally. Participants assigned to the comparator group will receive a daily dose of 75 mg of Clopidogrel Medreg. The maximum treatment duration for this group is also 12 months. Participant compliance with the dosing schedule will be closely monitored to maintain the integrity of the study data.

The clinical trial aims to assess the efficacy of CYP2C19-genotype-guided P2Y12 inhibitor selection in patients indicated for direct oral anticoagulants (D)OAC and requiring percutaneous coronary intervention (PCI). The primary efficacy endpoint is a composite measure of all-cause mortality, myocardial infarction, stroke, and stent thrombosis at 12 months. This will be compared to an objective performance goal (OPG) of 10.1% for patients treated with (D)OAC and P2Y12 inhibitors. Secondary efficacy evaluations will include subgroup analyses comparing the composite endpoint across four study groups: acute coronary syndrome (ACS) patients treated with **ticagrelor** versus those treated with **clopidogrel**, and elective patients treated with **ticagrelor** versus those treated with **clopidogrel**.

Data collection will occur at the 12-month mark, with efficacy outcomes being measured using validated clinical endpoints. Additionally, the EQ5D5L questionnaire will be utilized to generate a health state profile, allowing for comparisons of reported health problems across the patient groups. The trial will ensure that all efficacy assessments are conducted in a standardized manner to maintain the integrity and reliability of the data collected.