Prospective randomized comparison of effect on coronary endothelial and renal function between febuxostat and benzbromarone in hyperuricemic patients with coronary artery disease: EFEF study

Background and Aims There are two types of serum uric acid-lowering agents, the xanthine oxidoreductase (XO) inhibitor and non-XO inhibitor. We investigated whether febuxostat, XO inhibitor, could produce more favorable effects on coronary endothelial function (CEF) and renal function than benzbromarone, non-XO inhibitor, in hyperuricemic coronary artery disease (CAD) patients. Methods We divided 21 hyperuricemic patients with stenting for left anterior descending (LAD) or left circumflex (LCX) artery into patients started on febuxostat (F group) and those on benzbromarone (B group). After 8 months, all patients underwent CEF evaluations (acetylcholine provocation test) and optical coherence tomography (OCT) for non-culprit vessels (e.g. if patients received LAD stenting, we evaluated LCX). We compared the diameter ratio induced by acetylcholine and baseline (CEF ratio), thin-cap fibroatheroma and calcified plaque by OCT, uric acid, oxidative stress biomarkers, and renal function including estimated glomerular filtration rate (eGFR) between F and B groups. Creatinine 2 days after stenting was measured to evaluate contrast-induced nephropathy (CIN). Results Change of eGFR was significantly lower in F group (n= 11) than B group over 8 months while the other parameters including CEF ratio were similar. F group showed favorable effects for CIN. Conclusion In conclusion, 8-months of febuxostat, XO inhibitor, does not significantly protect CEF but can protect the renal function including CIN in hyperuricemic patients with CAD compared to benzbromarone, non-XO inhibitor.