Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis.
OBJECTIVE
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.
Mäki-Petäjä
Kaisa M
KM
Clinical Pharmacology Unit, University of Cambridge, Cambridge, United Kingdom. km391@cam.ac.uk
Booth
Anthony D
AD
Hall
Frances C
FC
Wallace
Sharon M L
SM
Brown
John
J
McEniery
Carmel M
CM
Wilkinson
Ian B
IB
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology*; D001384:Azetidines / Q000494:pharmacology* / Q000627:therapeutic use; D001783:Blood Flow Velocity; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects*; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013314:Stress, Mechanical
D000924:Anticholesteremic Agents; D001384:Azetidines; D008077:Lipoproteins, LDL; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe