POS0678 DOES SILDENAFIL IMPROVE ENDOTHELIAL DYSFUNCTION IN RHEUMATOID ARTHRITIS? – A PILOT CLINICAL TRIAL

Background: Rheumatoid arthritis (RA) is independently associated with an increased risk of cardiovascular disease (CVD). One the early stages atherosclerosis endothelial dysfunction, which in RA. Using drugs to target dysfunction a promising novel strategy for CVD prevention Sildenafil has been shown improve function diabetics, who have similar risk. Our hypothesis was that sildenafil use may be primary Objectives: To determine if RA patients improves (as measured by brachial artery flow-mediated dilation [FMD] and peripheral arterial tone [PAT]), as well serum inflammatory biomarkers. Methods: This NIH-funded study phase II, randomized double-blind placebo-controlled crossover efficacy trial 25 patients, no known history CVD, but at least one traditional factor. Patients were 1:1 receive either or placebo 3 months, then after 2-week washout, crossed over each respective group additional months. Vascular studies (FMD PAT) biomarkers (e-Selectin, ICAM-1, VCAM-1) performed baseline, months pre- post-washout, 6 Adverse events collected. Given cross-over design, analyses included random effects model within-subject comparisons versus periods, adjusting baseline EndoPAT) within period term treatment order. All tests 2-sided α=0.05. Results: A total 233 subjects assessed eligibility, being written informed consent. 13 first, 12 first. Baseline characteristics between those Placebo vs. Mean age 62.0+/-10.9 years; 84% female; 92% white. adverse experienced occurred. The endpoint (increase %FMD period) not significant (p=0.19). However, note powered 80% detect effect size 0.37 change biomarker sample 60, 25. increase (improvement) 0.200 units PAT ratio (p=0.003) compared placebo, adjusted order (within given period). Exploratory linear mixed models comparing e-Selectin, VCAM-1 level, did show any differences except ICAM-1 (55.3 higher p=0.011). Conclusion: In this pilot subjects, PAT. there difference FMD. limited due small size, impacted slow recruitment COVID-19 pandemic. Future larger are required assess whether other PDE5 inhibitors autoimmune high CVD. References: [1]Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart sudden deaths rheumatoid arthritis: population-based cohort study. Arthritis Rheum 2005;52:402-11. [2]Peters MJ, van Halm VP, Voskuyl AE, Does equal diabetes mellitus independent factor disease? prospective 2009;61:1571-9. [3]Deyoung L, Chung E, Kovac JR, Daily men type 2 diabetes. J Andrology 2012;33:176-80. Disclosure Interests: None declared