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CLINICAL RESEARCH

Ezetimibe and Simvastatin Reduce Inflammation, Disease Activity, and Aortic Stiffness and Improve Endothelial Function in Rheumatoid Arthritis

Kaisa M. Mäki-Petäjä, BSc^_*,_*, Anthony D. Booth, MD, MRCP^_*, Frances C. Hall, DPhil, FRCP, Sharon M.L. Wallace, BA, RN^_*, John Brown, DM, FRCP, Carmel M. McEniery, PhD^_* and Ian B. Wilkinson, DM, FRCP^_*

^_* Clinical Pharmacology Unit
Department of Clinical Medicine, Addenbrooke's Hospital
Trinity College, University of Cambridge, Cambridge, United Kingdom

Manuscript received February 6, 2007; revised manuscript received April 20, 2007, accepted April 22, 2007.

^_* Reprint requests and correspondence: Kaisa Mäki-Petäjä, Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, BOX 110, Cambridge CB2 0QQ, United Kingdom. (Email: km391{at}cam.ac.uk).

Objectives: The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in a cohort of rheumatoid arthritis (RA) patients.

Background: Rheumatoid arthritis is a chronic inflammatory condition associated with increased cardiovascular risk. Statins reduce inflammation and disease activity in RA patients, but whether this is due to pleiotropism or cholesterol lowering per se is unclear.

Methods: Twenty patients received 20 mg simvastatin or 10 mg ezetimibe each for 6 weeks in a randomized double-blind crossover study. Disease activity, blood pressure, aortic pulse wave velocity (PWV), brachial artery flow-mediated dilation (FMD), and serum inflammatory markers were measured before and after each treatment.

Results: Both ezetimibe and simvastatin significantly reduced total cholesterol (–0.62 ± 0.55 mmol/l and –1.28 ± 0.49 mmol/l, respectively; p < 0.001), low-density lipoprotein cholesterol (–0.55 ± 0.55 mmol/l and –1.28 ± 0.49 mmol/l; p < 0.0001), and C-reactive protein (–5.35 ± 9.25 mg/l and –5.05 ± 6.30 mg/l; p < 0.001). Concomitantly, Disease Activity Score (–0.55 ± 1.01 and –0.67 ± 0.91; p = 0.002), aortic PWV (–0.69 ± 1.15 m/s and –0.71 ± 0.71 m/s; p = 0.001), and FMD (1.37 ± 1.17% and 2.51 ± 2.13%; p = 0.001) were significantly improved by both drugs.

Conclusions: This study demonstrates that both ezetimibe and simvastatin reduce disease activity and inflammatory markers to a similar extent in patients with RA. Therapy is also associated with a concomitant reduction in aortic PWV and improvement in endothelial function. This suggests that cholesterol lowering per se has anti-inflammatory effects and improves vascular function in RA.

Abbreviations and Acronyms   AIx = augmentation index   CRP = C-reactive protein   DAS = Disease Activity Score   ESR = erythrocyte sedimentation rate   FMD = flow-mediated dilatation   GTN = glyceryl trinitrate   oxLDL = oxidized low-density lipoprotein   PWV = pulse wave velocity   RA = rheumatoid arthritis

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