Effects of selective and non‐selective cyclo‐oxygenase inhibition on endothelial function in patients with rheumatoid arthritis

OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk that has been attributed to endothelial dysfunction and inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase (COX)-2 inhibitors have been shown in some studies to improve endothelial function in subjects without RA. The aim of this study was to investigate the effects of COX inhibition on endothelial function in patients with RA. METHODS: Patients with RA (n = 37) were randomized to receive a 2-week course of either indomethacin (75 mg bd), rofecoxib (12.5 mg bd), or placebo in a double-blind study. Endothelial function was measured using flow-mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia. Arterial stiffness was also assessed using pulse wave analysis (PWA) through the measurement of the aortic augmentation index (AIx). Measurements of vascular function and inflammatory markers were taken before and at the end of the treatment period. RESULTS: There were no significant differences in changes in FMD, AIx, blood pressure (BP), serum creatinine, erythrocyte sedimentation rate (ESR), or high-sensitivity C-reactive protein (hsCRP) between groups. However, compared with the other treatment groups, there was a tendency for systolic BP to decrease in the placebo group (p = 0.063) and for creatinine to increase in the indomethacin and rofecoxib groups after treatment (p = 0.054). CONCLUSIONS: This study suggests that COX inhibition by indomethacin or rofecoxib do not improve endothelial function in patients with RA.