Carotid Ultrasound-Based Strategy for Primary Prevention of Cardiovascular Events in Inflammatory Rheumatic Disease (PREVENER) (PREVENER)

May 20, 2026 updated by: Instituto de Investigación Marqués de Valdecilla

Randomized Clinical Trial to Assess the Efficacy and Safety of a Primary Prevention Strategy for Cardiovascular Events in Patients With Inflammatory Rheumatic Diseases Based on the Use of Carotid Ultrasound

PREVENER is a randomized, open-label, multicenter, phase IV clinical trial designed to evaluate the efficacy and safety of a carotid ultrasound-based strategy for the primary prevention of cardiovascular events in patients with inflammatory rheumatic diseases (IRD).

Patients with IRD, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), and systemic lupus erythematosus (SLE), have a 50% higher risk of cardiovascular (CV) events compared to the general population. However, conventional CV risk scores (SCORE2/OP) systematically underestimate this risk, leaving many high-risk patients without appropriate preventive treatment.

Patients aged ≥50 years with IRD and low-to-moderate CV risk according to SCORE2/OP will be randomized 1:1 to either an experimental group (carotid ultrasound to detect subclinical atherosclerosis) or a control group (standard care according to ESC 2021 guidelines). Patients in the experimental group with carotid plaques will be reclassified as very high CV risk and treated with high-intensity statins (LDL target <55 mg/dL). The primary endpoint is the incidence of major adverse cardiovascular events (MACE) over 48 months of follow-up.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

Patients with chronic inflammatory rheumatic diseases (RA, PsA, AxSpA, SLE) carry a significantly increased risk of atherosclerotic cardiovascular events compared to the general population. This excess risk is largely attributed to the pro-atherogenic effect of chronic inflammation. Despite this, conventional CV risk stratification tools such as SCORE2/OP do not account for inflammation-related risk, leading to systematic underestimation of CV risk in these patients. Data from the CARMA project demonstrated that 53% of CV events in Spanish patients with IRD occurred in those classified as low-to-moderate risk by SCORE2/OP, highlighting the urgent need for improved risk stratification strategies.

Carotid ultrasound for the detection of subclinical atherosclerosis (carotid plaques) has been proposed as a modifier of CV risk in the ESC 2021 guidelines. The presence of carotid plaques automatically reclassifies individuals to very high CV risk, warranting intensive lipid-lowering therapy. However, no randomized clinical trial has evaluated the efficacy of this strategy in patients with IRD.

Study Design:

PREVENER is an open-label, randomized, multicenter, phase IV clinical trial. Patients aged ≥50 years with IRD (RA by ACR/EULAR 2010 criteria, PsA by CASPAR criteria, AxSpA by ASAS criteria, or SLE by ACR/EULAR 2019 criteria) and low-to-moderate CV risk according to SCORE2/OP will be enrolled across 17 Spanish hospitals.

Eligible patients will be randomized 1:1 to:

  • Experimental group: carotid ultrasound performed within 30 days of randomization. Patients with carotid plaques (defined by Mannheim consensus criteria) will be classified as very high CV risk and initiated on high-intensity statin therapy (LDL target <55 mg/dL). Patients without plaques will be managed according to ESC 2021 guidelines.
  • Control group: standard management according to ESC 2021 guidelines throughout the study.

Randomization will be performed using REDCap, stratified by age, sex, classic CV risk factors, lipid-lowering treatment, rheumatic disease, and advanced therapy use.

Primary Endpoint:

Incidence of major adverse cardiovascular events (MACE), defined as: acute myocardial infarction or stroke, hospitalization for unstable angina, arterial revascularization for peripheral arterial disease, or CV death.

Secondary Endpoints:

  1. Efficacy of the strategy analyzed individually by rheumatic disease (RA, PsA, AxSpA)
  2. Comparison of efficacy between men and women
  3. Safety comparison of adverse events between groups

Follow-up:

All patients will be followed for 48 months. Patients on lipid-lowering treatment will have monthly visits during the intensification phase (maximum 5 visits) until therapeutic target is achieved, followed by semi-annual visits until month 48. Patients not requiring lipid-lowering treatment will have semi-annual visits throughout.

Statistical Analysis:

The primary analysis will follow an intention-to-treat approach. Cox regression models will be used to calculate Hazard Ratios with 95% confidence intervals, adjusted for relevant covariates. Kaplan-Meier survival curves will be compared using the log-rank test. A sample size of 1,944 patients provides 80% power to detect a 50% reduction in CV events in the experimental group (alpha=0.05). An interim analysis will be performed at 50% of expected events using the O'Brien-Fleming stopping rule, reviewed by an independent Data Safety Monitoring Board (DSMB).

Study Type

Interventional

Enrollment (Estimated)

1944

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Alicante
      • Alicante, Alicante, Spain
      • Elche, Alicante, Spain
      • Orihuela, Alicante, Spain
        • Recruiting
        • Hospital Vega Baja de Orihuela
        • Contact:
    • Barcelona
      • Barcelona, Barcelona, Spain
    • Cantabria
      • Laredo, Cantabria, Spain
      • Santander, Cantabria, Spain
        • Not yet recruiting
        • Hospital Universitario Marqués de Valdecilla
        • Contact:
      • Torrelavega, Cantabria, Spain
    • Ciudad Real
      • Ciudad Real, Ciudad Real, Spain
        • Not yet recruiting
        • Hospital General Universitario de Ciudad Real
        • Contact:
    • Córdoba
      • Córdoba, Córdoba, Spain
        • Not yet recruiting
        • Hospital Universitario Reina Sofía
        • Contact:
    • Isla Baleares
      • Palma, Isla Baleares, Spain
        • Not yet recruiting
        • Hospital Universitari Son LLàtzer
        • Contact:
    • Las Palmas
      • Las Palmas de Gran Canaria, Las Palmas, Spain
        • Not yet recruiting
        • Hospital Universitario de Gran Canaria Dr. Negrin
        • Contact:
    • Madrid
      • Madrid, Madrid, Spain
      • Madrid, Madrid, Spain
        • Not yet recruiting
        • Hospital Universitario Ramon y Cajal
        • Contact:
    • Murcia
      • Murcia, Murcia, Spain
        • Not yet recruiting
        • Hispital Universitario Virgen de la Arrixaca
        • Contact:
    • Santa Cruz de Tenerife
      • San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
    • Vizcaya
      • Bilbao, Vizcaya, Spain
        • Recruiting
        • Hospital Universitario de Basurto
        • Contact:
    • Álava
      • Vitoria-Gasteiz, Álava, Spain
        • Recruiting
        • Hospital Universitario Araba
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients aged ≥50 years who have provided written informed consent.

  2. Fulfillment of classification criteria for at least one of the following inflammatory rheumatic diseases:

    • Rheumatoid arthritis (RA) according to ACR/EULAR 2010 criteria
    • Psoriatic arthritis (PsA) according to CASPAR criteria
    • Axial spondyloarthritis (AxSpA) according to ASAS criteria
    • Systemic lupus erythematosus (SLE) according to ACR/EULAR 2019 criteria
  3. Low-to-moderate cardiovascular risk according to SCORE2/OP classification.

Exclusion Criteria:

  1. Presence of previous cardiovascular events, type 2 diabetes mellitus, familial hypercholesterolemia, or chronic kidney disease resulting in classification as high or very high cardiovascular risk.
  2. Prior carotid ultrasound examination with subsequent therapeutic intervention derived from its results, either in the context of a research study or routine clinical practice.
  3. Contraindications to lipid-lowering therapy, including recent history of alcoholism, active liver disease, or unexplained and persistent elevation of serum transaminases exceeding three times the upper limit of normal (applicable to statins and ezetimibe).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Group: Carotid Ultrasound
Patients undergo carotid ultrasound within 30 days of randomization. Patients with carotid plaques are reclassified as very high cardiovascular risk and initiated on high-intensity statin therapy (LDL target < 55 mg/dL). Patients without carotid plaques are managed according to ESC 2021 guidelines.
Diagnostic test: Carotid Ultrasound
Carotid ultrasound performed to detect subclinical atherosclerosis (carotid plaques) according to Manheim consensus criteria. The presence of carotid plaques triggers reclassification to very high cardiovascular risk and initiation of high-intensity lipid-loqering therapy
Drug: High-intensity lipid-lowering therapy
Sequential lipid-lowering therapy initiated in experimental group patinets with carotid plaques, targeting LDL < 55 mg/dL. Treatment includes high-intensity statins (atorvastatin 40-80mg, rouvastatin 20-40mg), with possible addition of azetimibe, bempedoic acid, and/or PCSK9 inhibitors if target is not achieved.
Active Comparator: Control Group: Standard Care
Patients are managed according to standard ESC 2021 cardiovascular prevention guidelines throughout the study, without carotid ultrasound assessment.
Other: Standard care according to ESC 2021 guidelines
Lipid-lowerin treatment indicated and managed according to ESC 2021 cardiovascular prevention guidelines, based on SCORE/OP risk stratification, without carotid ultrasound assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Major Adverse Cardiovascular Events (MACE)
Time Frame: 48 months
48 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing an Acute Myocardial Infarction or Stroke
Time Frame: 48 months
Incidence of acute myocardial infarction or stroke during the follow-up period.
48 months
Number of Participants Hospitalized for Unstable Angina
Time Frame: 48 months
Incidence of hospital admissions due to unstable angina during the follow-up period.
48 months
Number of Participants Requiring Arterial Revascularization for Peripheral Arterial Disease
Time Frame: 48 months
Incidence of arterial revascularization procedures required for peripheral arterial disease during the follow-up period.
48 months
Number of Participants Experiencing Cardiovascular Death
Time Frame: 48 months
Incidence of cardiovascular death during the follow-up period.
48 months
Number of Participants Experiencing a Major Cardiovascular Event. Stratified by Rheumatic Disease Subgroup
Time Frame: 48 months
Evaluation of the incidence of major cardiovascular events (acute myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization for peripheral artery disease, or cardiovascular death) analyzed individually for each included inflammatory disease (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and systemic lupus erythematosus).
48 months
Number of Participants Experiencing a Major Cardiovascular Event. Analyzed by Sex
Time Frame: 48 months
This measure evaluates the efficacy of the strategy by comparing the incidence of individual cardiovascular events (acute myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization or cardiovascular death) between male and female participants.
48 months
Incidence of adverse events
Time Frame: 48 months
48 months
LDL cholesterol levels
Time Frame: 48 months
48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto de Investigación Marqués de Valdecilla

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 22, 2026

Primary Completion (Estimated)

April 22, 2031

Study Completion (Estimated)

December 1, 2031

Study Registration Dates

First Submitted

May 14, 2026

First Submitted That Met QC Criteria

May 20, 2026

First Posted (Actual)

May 28, 2026

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PREVENER
  • 2025-521086-28-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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