Abstract 14636: The Effects of Celecoxib on Endothelial Function in Healthy Volunteers; A Double Blind, Placebo Controlled Randomised Trial

Abstract

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs), which work by blocking cyclooxygenase (COX)-2 can increase cardiovascular risk by up to 30% after 2 weeks of use and in animal models augments thrombosis. However, the effect of NSAIDs and loss of COX-2 on endothelial function and blood flow remains incompletely understood. A plausible explanation is inhibition of COX-2 affects endothelial function by inhibiting prostacyclin and/or reducing endothelial nitric oxide synthase (eNOS) activity/expression. We hypothesised that COX-2 inhibition with celecoxib will impact on endothelial function. Methods: Healthy male volunteers aged between 18 to 40 were randomised 1:1 to receive either celecoxib (200 mg twice daily) or matching placebo for 7 days. The primary outcome was change (Δ) in endothelial function assessed using the EndoPAT device. Participants were given a home blood pressure machine and diary as a secondary outcome measure. Participants and outcome assessors were blinded to the intervention. Results: Between June 2021 and January 2022, 44 participants were randomised of which 40 participants completed the study (20 allocated to each arm) and were included in the final analysis. Baseline characteristics were similar between the groups. Compared to placebo, there was a significant increase in augmentation index (AI) following celecoxib use: Δ 6.2; (95% CI 0.05 to 12.4) p:0.048. There was no difference in log reactive hyperaemia index (LnRHI): Δ -0.092; (95% CI -0.31 to 0.12) p:0.39, systolic blood pressure: Δ -3.5; (95% CI -9.9 to 3) p:0.28, or diastolic blood pressure: Δ 4.7; (95% CI -1.8 to 11.1) p:0.15 (Figure) . Conclusion: In healthy male volunteers, 7 days of treatment with celecoxib significantly increased augmentation index which is a surrogate for vascular stiffness and an independent predictor of cardiovascular risk. Further clinical and mechanistic studies are required to elucidate how COX-2 inhibition impacts on augmentation index.