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
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.
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:
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:
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).
Inclusion Criteria:
Patients aged ≥50 years who have provided written informed consent.
Fulfillment of classification criteria for at least one of the following inflammatory rheumatic diseases:
Low-to-moderate cardiovascular risk according to SCORE2/OP classification.
Exclusion Criteria:
Alicante, Alicante, Spain
soficarballido@hotmail.com
Las Palmas de Gran Canaria, Las Palmas, Spain
San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain
CYNTHIA.ROMERA.LOPEZ@hotmail.com
mpmavidal@yahoo.es
alba.erra@vallhebron.cat
c.corrales.selaya@gmail.com
vcalvorio@gmail.com
ruedagotor@gmail.com
d.castrocorredor@gmail.com
mangeles.puche@gmail.com
iros@hsll.es
iferrazamaro@hotmail.com
eugenio.demiguel@gmail.com
martavaleroex@yahoo.es
mjmorenoramos@gmail.com
iferrazamaro@hotmail.com
marilugv@hotmail.com
jcalvo@ser.es