Efficacy of Beta-Blockers and Antiplatelet Agents in Spontaneous Coronary Artery Dissection: A Randomized Clinical Trial

The primary objective of this randomized clinical trial is to assess the **efficacy** of medical therapy, specifically **β-blockers** and **antiplatelet agents**, in patients with **Spontaneous Coronary Artery Dissection (SCAD)**. This evaluation is clinically relevant as it aims to determine the effectiveness of these medications in managing SCAD, a condition that can lead to acute coronary syndrome and is associated with significant morbidity.

Secondary objectives include:

• Angiographic and Quantitative Coronary Analyses (QCA).
• Coronary revascularization, focusing on the selection of ideal candidates and optimization of coronary intervention results.
• Intracoronary imaging using optical coherence tomography (OCT) and intravascular ultrasound (IVUS).
• Cardiac CT.
• Magnetic resonance imaging (MRI).
• Pharmacogenetics.
• Inflammatory, immunologic, genetic, and micro-RNA analyses.

The clinical trial focuses on patients diagnosed with **Spontaneous Coronary Artery Dissection** (SCAD). The study population includes both male and female participants, with an age range corresponding to categories 3 and 4, which typically represent adults and middle-aged individuals. The trial involves a vulnerable population, although the specific number of participants has not been disclosed by the sponsor. Participants were selected based on their admission for acute coronary syndrome (ACS) or other manifestations of myocardial ischemia, with a confirmed diagnosis of SCAD via coronary angiography during their index hospitalization. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include obtaining written informed consent from participants. The sponsor has not provided additional information regarding the general health status or specific lifestyle habits of the participants.

The clinical trial is designed to evaluate the efficacy of **beta-blockers** and **antiplatelet agents** in patients diagnosed with **Spontaneous Coronary Artery Dissection** (SCAD). This study is a randomized, double-blind, controlled trial, classified as a low-intervention trial by the Spanish Health Authorities. The trial is set to span a duration of approximately four and a half years, with an estimated end date of February 28, 2026. Participants will be involved in the study for a maximum treatment period of 12 months.

The trial will commence with an inclusion visit, where participants will undergo screening to ensure they meet the principal inclusion criteria, which include providing written informed consent, being admitted for acute coronary syndrome (ACS) or other manifestations of myocardial ischemia, and having a diagnosis of SCAD confirmed by coronary angiography during the index hospitalization. Following the inclusion visit, participants will be randomly assigned to receive either beta-blockers or antiplatelet agents, administered orally, as per the trial protocol.

Study visits will be scheduled at regular intervals to monitor the participants' health status and treatment efficacy. These visits will include assessments of the primary endpoint, which is a combined clinical endpoint encompassing death, myocardial infarction (MI), stroke, coronary revascularization, recurrent dissection, and hospital admission for ACS or heart failure at a 1-year follow-up. Secondary endpoints will also be evaluated, including a secondary combined clinical endpoint to assess the net clinical benefit of the antiplatelet strategy, and bleeding events defined according to BARC definitions.

The end-of-study visit will mark the conclusion of the participant's involvement in the trial, where final assessments will be conducted to gather comprehensive data on the treatment outcomes. Participants may be subject to early termination from the study if they experience adverse events that compromise their safety, withdraw consent, or fail to comply with the study protocol. The trial aims to provide valuable insights into the management of SCAD, potentially influencing future therapeutic strategies for this condition.

The clinical trial involves the administration of several **experimental medications** to assess their efficacy in patients with Spontaneous Coronary Artery Dissection (SCAD). The first medication is **Carbasalate Calcium**, known by its synonym **Carbaspirin Calcium**. It is administered orally in a pharmaceutical form identified as PHF00059MIG. The maximum daily dose is 300 mg, with a total maximum dose of 109,500 mg over a 12-month period. This medication functions as an antiplatelet agent.

**Prasugrel Hydrobromide** is another experimental medication used in the trial. It is administered orally in the pharmaceutical form PHF00082MIG. The maximum daily dose is 60 mg, with a total maximum dose of 21,900 mg over the course of 12 months. Prasugrel Hydrobromide also serves as an antiplatelet agent.

**Metoprolol Succinate** is included in the study as a **betablocker**. It is administered orally in the pharmaceutical form PHF00212MIG. The maximum daily dose is 400 mg, with a total maximum dose of 146,000 mg over a 12-month period.

**Propranolol Hydrochloride** is another betablocker used in the trial. It is administered orally in the pharmaceutical form PHF00231MIG. The maximum daily dose is 640 mg, with a total maximum dose of 233,600 mg over 12 months.

**Atenolol** combined with **Chlortalidone** is administered as a betablocker. The oral pharmaceutical form is PHF00009MIG. The maximum daily dose is 100 mg, with a total maximum dose of 36,500 mg over a 12-month period.

**Perindopril Tert-Butylamine**, also known as **Perindopril Erbumine**, is administered as a betablocker. It is given orally in the pharmaceutical form PHF00245MIG. The maximum daily dose is 100 mg, with a total maximum dose of 36,500 mg over 12 months.

**Telmisartan** is administered as an antiplatelet agent. It is given orally in the pharmaceutical form PHF00245MIG. The maximum daily dose is 300 mg, with a total maximum dose of 109,500 mg over a 12-month period.

**Bisoprolol Fumarate** combined with **Hydrochlorothiazide** is administered as a betablocker. It is given orally in the pharmaceutical form PHF00082MIG. The maximum daily dose is 10 mg, with a total maximum dose of 3,650 mg over 12 months.

**Ticagrelor**, also known as **AZD6140**, is administered as an antiplatelet agent. It is given orally in the pharmaceutical form PHF00082MIG. The maximum daily dose is 180 mg, with a total maximum dose of 65,700 mg over a 12-month period.

All medications are administered orally, and participant compliance is monitored throughout the trial. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The study aims to evaluate the efficacy of these medications in managing SCAD over a 12-month treatment period.

The efficacy of the medical therapy involving **β-blockers** and antiplatelet agents in patients with Spontaneous Coronary Artery Dissection (SCAD) will be assessed through a randomized clinical trial. The primary endpoint for evaluating efficacy is a combined clinical endpoint, which includes death, myocardial infarction (MI), stroke, coronary revascularization, recurrent dissection, and hospital admission for acute coronary syndrome (ACS) or heart failure at a 1-year follow-up. Secondary endpoints will include a secondary combined clinical endpoint to assess the "net clinical benefit" of the antiplatelet strategy, bleeding as a separate safety endpoint defined according to BARC definitions, and individual components of the primary endpoint. Additionally, a major predefined secondary combined endpoint will be the composite outcome measure of "hard" clinical events, including death, MI, stroke, recurrent dissection, and coronary revascularization, as well as the combined outcome measure of death and MI alone.