Randomized clinical trial to assess the efficacy and safety of a strategy for primary prevention of cardiovascular disease in patients with inflammatory rheumatic diseases based on the use of carotid ultrasound.

The primary objective is to analyze the efficacy of a primary prevention strategy for cardiovascular events in patients with inflammatory rheumatic diseases based on the use of carotid ultrasound to identify and treat those patients at high cardiovascular risk classified in the low-moderate SCORE groups, comparing it with the current strategy based on clinical guidelines. This objective addresses the clinical need for improved cardiovascular risk stratification in patients with chronic inflammatory rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and systemic lupus erythematosus, who are at elevated cardiovascular risk.

The secondary objectives are:

• To analyze individually the efficacy of this strategy in each of the diseases included (rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis).

• To compare the efficacy of this strategy in men and women.

• To analyze the safety of the strategy by comparing the adverse effects of the intervention group and those of the control group.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population includes adult and elderly patients aged **50 years and older** diagnosed with **chronic inflammatory rheumatic diseases**, specifically **rheumatoid arthritis**, **psoriatic arthritis**, **axial spondyloarthritis**, or **systemic lupus erythematosus**. Both **male** and **female** subjects are eligible for participation. Participants are selected based on meeting established classification criteria for their respective rheumatic conditions and being classified in the low-moderate **cardiovascular risk** groups according to SCORE2/OP assessment. All participants must provide written **informed consent** prior to enrollment. The trial population does not include vulnerable populations. No specific information regarding lifestyle considerations such as diet, physical activity, or habits was provided by the sponsor.

This clinical trial evaluates the efficacy and safety of a cardiovascular disease primary prevention strategy in patients with chronic inflammatory rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, or systemic lupus erythematosus. The study is designed as a randomized clinical trial comparing a prevention strategy based on carotid ultrasound assessment to identify and treat patients at high cardiovascular risk classified in low-moderate SCORE groups, versus the current strategy based on clinical guidelines. The trial is classified as a low-intervention Phase IV study, as carotid ultrasound use for this purpose is already contemplated in clinical practice guidelines, and the prevention strategy does not entail additional risks compared to standard practice. The investigational medicinal products include bempedoic acid administered orally at a maximum daily dose of 180 mg, rosuvastatin and ezetimibe combination at a maximum daily dose of 40 mg, and atorvastatin and amlodipine combination at a maximum daily dose of 80 mg. These medications serve as lipid-lowering agents and are approved products with established safety profiles. The maximum treatment period for all study medications is 48 weeks.

The primary objective is to analyze the efficacy of the ultrasound-guided prevention strategy in patients with inflammatory rheumatic diseases by identifying and treating those at high cardiovascular risk. The primary endpoint is the occurrence of a major cardiovascular event, including acute myocardial infarction, stroke, hospital admission for unstable angina, arterial revascularization for peripheral artery disease, or death due to cardiovascular disease. Secondary endpoints include the individualized appearance of each cardiovascular event that comprises the primary endpoint.

Eligible participants include patients aged 50 years or older who meet classification criteria for rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, or systemic lupus erythematosus, and who are classified in the low-moderate cardiovascular risk groups according to SCORE2/OP. All participants must provide written informed consent prior to enrollment. The estimated recruitment start date is January 1, 2026, with an estimated study completion date of December 3, 2029, resulting in an overall trial duration of approximately 4 years.

Participant involvement extends throughout the treatment period of up to 48 weeks, with follow-up continuing until the end of the study to monitor for cardiovascular events. Study visits include a screening visit to assess eligibility criteria and obtain informed consent, treatment visits for medication administration and monitoring, and follow-up visits to evaluate efficacy and safety outcomes. An end-of-study visit will be conducted to complete final assessments. Early termination from the study may occur based on participant withdrawal of consent, occurrence of adverse events requiring discontinuation, protocol violations, or investigator decision based on safety concerns.

The experimental treatment regimen consists of multiple lipid-lowering agents administered according to individual patient requirements. Bempedoic acid is administered as a tablet formulation via oral route at a maximum daily dose of 180 mg. The treatment duration extends up to 48 weeks. This agent serves as one of the test products in the trial and belongs to the class of lipid-modifying medications.

A fixed-dose combination product containing rosuvastatin calcium and ezetimibe, with lactose monohydrate as an excipient, is utilized in tablet form for oral administration. The maximum daily dose is 40 mg, with a maximum total dose of 40 mg. This combination product functions both as a test medication and as a comparator treatment within the study design. The treatment period for this combination extends up to 48 weeks or 48 days, depending on the treatment arm assignment.

A combination product of atorvastatin and amlodipine is administered as a tablet via oral route at a maximum daily dose of 80 mg. This fixed-dose combination serves as a test product and is administered for a maximum treatment period of 48 weeks. All medicinal products in this trial are classified as lipid-lowering agents and are part of a cardiovascular disease prevention strategy.

All investigational products are administered orally in tablet formulation. The dosing regimen is individualized based on patient assessment and cardiovascular risk stratification using carotid ultrasound findings. Treatment compliance monitoring is conducted throughout the 48-week treatment period to ensure adherence to the prescribed therapeutic regimen.

The primary efficacy endpoint is defined as the occurrence of a major cardiovascular event, which includes acute myocardial infarction, stroke, hospital admission for unstable angina, arterial revascularization for peripheral artery disease, or death due to cardiovascular disease. Secondary efficacy endpoints consist of the individualized appearance of each of the cardiovascular events that comprise the primary endpoint. The trial will evaluate the efficacy of a primary prevention strategy for cardiovascular events in patients with inflammatory rheumatic diseases based on the use of carotid ultrasound to identify and treat patients at high cardiovascular risk classified in the low-moderate SCORE groups, comparing this approach with the current strategy based on clinical guidelines. The maximum treatment period is 48 weeks, with an estimated recruitment start date in January 2026 and an estimated study completion date in December 2029.