Background and Aims: HMG-CoA reductase inhibitors (statins) have been shown to have anti-inflammatory and disease modifying properties in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation, disease activity, arterial stiffness and endothelial function in patients with RA and to test our hypothesis that cholesterol lowering per se can improve arterial stiffness and reduce inflammation.

Methods: 20 RA patients received simvastatin 20 mg and ezetimibe 10mg in a double-blind cross over study. Blood pressure, aortic pulse wave velocity (PWV) and flow mediated dilatation response (FMD) were measured before and after each treatment. Serum inflammatory markers and disease activity were also determined. Data are mean changes±SEM, and significance was determined using 2-way repeated measures ANOVA.

Results: As expected both ezetimibe and simvastatin significantly reduce total cholesterol (−0.62±0.12 and −1.28±0.11 mmol/L, respectively; P <0.0001). Both drugs significantly reduced CRP (−5.35±2.07 and −5.05±1.41 mg/L; P = 0.0002); disease activity (−0.74±0.24 and −0.50±0.18; P <0.0001); aortic PWV (−0.69±0.26 and −0.71±0.16 m/s; P = 0.0012) and concomitantly, FMD was significantly improved (1.37±0.26 and 2.51±0.48%; P = 0.0001). Importantly, only the effect on total cholesterol differed significantly between the drugs (P <0.001).

Conclusion: The present study shows, that both ezetimibe and simvastatin reduce inflammatory markers and disease activity to a similar extend in patients with RA. Moreover, aortic PWV was reduced with both drugs and concomitantly, endothelial function was improved. This suggests that cholesterol lowering per se has anti-inflammatory effects and improves vascular function.