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

5 november 2026 uppdaterad av: 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.

Studieöversikt

Status

Rekrytering

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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).

Studietyp

Interventionell

Inskrivning (Beräknad)

1944

Fas

  • Fas 4

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Spanien
    • Alicante
      • Alicante, Alicante, Spanien
      • Elche, Alicante, Spanien
      • Orihuela, Alicante, Spanien
        • Rekrytering
        • Hospital Vega Baja de Orihuela
        • Kontakt:
    • Barcelona
      • Barcelona, Barcelona, Spanien
    • Cantabria
      • Laredo, Cantabria, Spanien
      • Santander, Cantabria, Spanien
        • Har inte rekryterat ännu
        • Hospital Universitario Marqués de Valdecilla
        • Kontakt:
      • Torrelavega, Cantabria, Spanien
    • Ciudad Real
      • Ciudad Real, Ciudad Real, Spanien
        • Har inte rekryterat ännu
        • Hospital General Universitario de Ciudad Real
        • Kontakt:
    • Córdoba
      • Córdoba, Córdoba, Spanien
        • Har inte rekryterat ännu
        • Hospital Universitario Reina Sofía
        • Kontakt:
    • Isla Baleares
      • Palma, Isla Baleares, Spanien
        • Har inte rekryterat ännu
        • Hospital Universitari Son LLàtzer
        • Kontakt:
    • Las Palmas
      • Las Palmas de Gran Canaria, Las Palmas, Spanien
        • Har inte rekryterat ännu
        • Hospital Universitario de Gran Canaria Dr. Negrín
        • Kontakt:
    • Madrid
      • Madrid, Madrid, Spanien
      • Madrid, Madrid, Spanien
        • Har inte rekryterat ännu
        • Hospital Universitario Ramón y Cajal
        • Kontakt:
    • Murcia
      • Murcia, Murcia, Spanien
        • Har inte rekryterat ännu
        • Hispital Universitario Virgen de la Arrixaca
        • Kontakt:
    • Santa Cruz de Tenerife
      • San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spanien
        • Har inte rekryterat ännu
        • Hospital Universitario de Canarias
        • Kontakt:
    • Vizcaya
      • Bilbao, Vizcaya, Spanien
        • Rekrytering
        • Hospital Universitario de Basurto
        • Kontakt:
    • Álava
      • Vitoria-Gasteiz, Álava, Spanien
        • Rekrytering
        • Hospital Universitario Araba
        • Kontakt:

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

50 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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).

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Förebyggande
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Diagnostiskt 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

Läkemedel: 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.
Aktiv komparator: Control Group: Standard Care

Patients are managed according to standard ESC 2021 cardiovascular prevention guidelines throughout the study, without carotid ultrasound assessment.
Övrig: 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

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
Incidence of Major Adverse Cardiovascular Events (MACE)
Tidsram: 48 months
48 months

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Incidence of adverse events
Tidsram: 48 months
48 months
LDL cholesterol levels
Tidsram: 48 months
48 months
Number of Participants Experiencing an Acute Myocardial Infarction or Stroke
Tidsram: 48 months

Incidence of acute myocardial infarction or stroke during the follow-up period.
48 months
Number of Participants Hospitalized for Unstable Angina
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Instituto de Investigación Marqués de Valdecilla

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

22 april 2026

Primärt slutförande (Beräknad)

22 april 2031

Avslutad studie (Beräknad)

1 december 2031

Studieregistreringsdatum

Först inskickad

14 maj 2026

Först inskickad som uppfyllde QC-kriterierna

20 maj 2026

Första postat (Faktisk)

28 maj 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

10 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

5 november 2026

Senast verifierad

1 maj 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • PREVENER
  • 2025-521086-28-00 (Ctis)
  • 2025 (U.S.S. NIH-anslag/kontrakt)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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