Randomized, Controlled, Double-Blind Trial on the Impact of Rosuvastatin on Sublinical Markers of Atherosclerosis in Patients with ANCA-Associated Vasculitis

Benjamin Terrier¹, Gregory Pugnet², Marie-Emmanuelle Sirieix³, Thomas Quemeneur⁴, Xavier Puéchal⁵, Francois Maurier⁶, Antoine Néel⁷, YGAL BENHAMOU⁸, Bernard Bonnotte⁹, Jean Schmidt¹⁰, Adrien Michon³, Antoine Baudet¹¹, Pierre Charles¹², Fleur Cohen¹³, Claire De Moreuil¹⁴, Emanuelle Dernis¹⁵, Pauline Belenotti¹⁶, Marc Ruivard¹⁷, Olivier Aumaitre¹⁸, Olivier Fain¹⁹, Raphaele Seror²⁰, Cécile-Audrey Durel²¹, Noémie Jourde-Chiche²², Estibaliz Lazaro²³, Gilles Chironi²⁴, Guillaume Armengol²⁵, Jeremy Bellien²⁵, Philippe Ravaud²⁶, Gabriel Baron²⁶ and Loic Guillevin²⁷, ¹Department of Internal Medicine, Hôpital Cochin, AP-HP, Paris, France, ²CHU Toulouse Rangueil Service de Medecine Interne et Immunologie Clinique, Toulouse, France, ³HEGP, Paris, France, ⁴CH Valenciennes, Valenciennes, France, ⁵National Referral Center for Rare Systemic Autoimmune Diseases, Paris, France, ⁶Hôpitaux privés de Metz, Vaux / Frankreich, France, ⁷CHU Nantes, Nantes, France, ⁸rouen university hospital, Rouen, France, ⁹Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France, ¹⁰CHU Amiens, Amiens, France, ¹¹CH Annecy, Annecy, France, ¹²Institut Mutualiste Montsouris, Service de Médecine Interne, Paris, France, ¹³Sorbonne Université, Paris, France, ¹⁴CHU de Brest, Brest, France, ¹⁵CH Le Mans, Le Mans, France, ¹⁶CHU Marseille, Marseille, France, ¹⁷CHU Clermont Ferrand, Clermont Ferrand, France, ¹⁸CHU Saint Antoine, Paris, France, ¹⁹Hopital SAINT ANTOINE APHP, Paris, France, ²⁰University Hospital Paris Saclay, Le Kremlin-Bicêtre, France, ²¹CHU Lyon, Lyon, France, ²²AP-HM, Marseille, France, ²³Bordeaux Hospital University, Pessac, France, ²⁴Monaco, Monaco, Monaco, ²⁵CHU Rouen, Rouen, France, ²⁶Paris Cité University, Paris, France, ²⁷University Paris Descartes, Paris, France

Meeting: ACR Convergence 2023

Keywords: ANCA associated vasculitis, Cardiovascular, prevention, Vasculitis

Session Information

Date: Sunday, November 12, 2023

Title: Abstracts: Vasculitis – ANCA-Associated I

Session Type: Abstract Session

Session Time: 4:00PM-5:30PM

Background/Purpose: Despite more effective therapeutic strategies in ANCA-associated vasculitis (AAV), there is still a significant risk of morbidity and mortality, mainly due to infection, and cardiovascular disease. Carotid intima-media thickness (cIMT) is a marker of subclinical atherosclerosis associated with cardiovascular risk factors and is predictive of major cardiovascular events (MACE). We hypothesized that patients with AAV might benefit from statin treatment in primary prevention to reduce subclinical markers of atherosclerosis and the incidence of major cardiovascular events.

Methods: This phase 3, multicentre, randomized, controlled, double-blind, superiority study compared rosuvastatin with placebo in reducing the progression of subclinical markers of atherosclerosis. Patients with AAV in remission after a first flare or relapse were randomized 1:1 to receive the experimental strategy based on the use of rosuvastatin 20 mg/day or placebo for 24 months. The primary endpoint was the mean change in mean cIMT (distal wall of primary carotid arteries) at 24 months.

Results: A total of 111 participants underwent randomization (55% male, mean age 54.8 (13.3) years, 63.1% GPA, 28.8% EGPA, 8.1% MPA), with 54 participants assigned to receive rosuvastatin and 57 to placebo.

The primary endpoint was not met. The mean change in cIMT at month 24 was not different between the two study groups (difference -0.002 [-0.034 ; 0.030], p=0.89) (Figure 1). The annualized rate of change in mean cIMT was 0.0110 (0.0617) mm/year in the rosuvastatin group and 0.0189 (0.0556) mm/year in the placebo group (difference -0.0062 [-0.0318 ; 0.0193], p=0.61). Similar results were found for the mean change in the number of plaques in the carotid and femoral arteries and abdominal aorta (difference 0.01 [-0.39 ; 0.42], p=0.94).

Mean LDL-cholesterol levels were significantly different between the two study groups at all time points evaluated (P< 0.001, P< 0.001, and P< 0.001 for reductions between the rosuvastatin and the placebo groups at months 6, 12 and 24, respectively) (Figure 2). Also, high-sensitivity CRP levels were significantly different between the two study groups at month 24 (difference -3.16 [-5.58 ; 0.74], p=0.011 for reductions between the rosuvastatin and the placebo groups).

There was only one MACE in the rosuvastatin group. Vasculitis relapse-free survival did not differ between the two groups (HR 1.59, 95%IC = [0.81 ; 3.09], p=0.18).

Eleven and seventeen patients discontinued intervention in the rosuvastatin and the placebo groups, respectively. The incidence of serious adverse events was similar in the two groups: 27.8% in the rosuvastatin group and 22.8% in the placebo group.

Conclusion: Among patients with ANCA-associated vasculitis, 24 months of rosuvastatin reduced LDL-cholesterol but did not reduce the progression of subclinical markers of atherosclerosis (Funded by the French Ministry of Health; STATVAS ClinicalTrials.gov number, NCT02117453).

Figure 1. Evolution of mean carotid intima-media thickness (in mm) during the study period in the two groups. Rosuvastatin arm is group A and placebo arm is group B.

Figure 2. Evolution of mean LDL-cholesterol (in mmol/L) during the study period in the two groups. Rosuvastatin arm is group A and placebo arm is group B.

Disclosures: B. Terrier: AstraZeneca, 5, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2; G. Pugnet: None; M. Sirieix: None; T. Quemeneur: None; X. Puéchal: None; F. Maurier: None; A. Néel: None; Y. BENHAMOU: None; B. Bonnotte: None; J. Schmidt: None; A. Michon: None; A. Baudet: None; P. Charles: None; F. Cohen: None; C. De Moreuil: None; E. Dernis: AbbVie/Abbott, 2, Amgen, 2, Bristol-Myers Squibb(BMS), 2, Celgene, 2, Eli Lilly, 2, Galapagos, 2, Gilead, 2, Janssen, 2, MSD, 2, Nordic Pharma, 2, Novartis, 2, Pfizer, 2, Roche, 2, Roche-Chugai, 2, Sandoz, 2, Sanofi, 2, UCB Pharma, 2; P. Belenotti: None; M. Ruivard: None; O. Aumaitre: None; O. Fain: None; R. Seror: None; C. Durel: None; N. Jourde-Chiche: None; E. Lazaro: None; G. Chironi: None; G. Armengol: None; J. Bellien: None; P. Ravaud: None; G. Baron: None; L. Guillevin: None.

To cite this abstract in AMA style:

Terrier B, Pugnet G, Sirieix M, Quemeneur T, Puéchal X, Maurier F, Néel A, BENHAMOU Y, Bonnotte B, Schmidt J, Michon A, Baudet A, Charles P, Cohen F, De Moreuil C, Dernis E, Belenotti P, Ruivard M, Aumaitre O, Fain O, Seror R, Durel C, Jourde-Chiche N, Lazaro E, Chironi G, Armengol G, Bellien J, Ravaud P, Baron G, Guillevin L. Randomized, Controlled, Double-Blind Trial on the Impact of Rosuvastatin on Sublinical Markers of Atherosclerosis in Patients with ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/randomized-controlled-double-blind-trial-on-the-impact-of-rosuvastatin-on-sublinical-markers-of-atherosclerosis-in-patients-with-anca-associated-vasculitis/. Accessed .

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