Uric-Acid Lowering Treatment by a Xanthine Oxidase Inhibitor Improved the Diastolic Function in Patients with Hyperuricemia

Objective Hyperuricemiais often observed in patients with chronic heart failure (CHF), and it is predictive of poor exercise capacity, inflammation and increased mortality. The uric acid (UA)-generating enzyme xanthine oxidase(XO) is a major source of reactive oxygen species (ROS) generation, and increased ROS has been accounted for multiple adverse effects in CHF pathophysiology. Therapeutic inhibition of XO with allopurinolreduced serum UA (SUA) levels and showed a range of beneficial effects in CHF with left ventricular (LV) systolic dysfunction. However, it is unclear if UA-lowering therapy by XO inhibition is beneficial in patients with LV diastolicdysfunction. Therefore, we evaluated the effects of the specific XO inhibitor febuxostaton LV diastolic functioncompared with the uricosuricagent benzbromarone. Methods and Results The effects of febuxostatand benzbromarone(24 weeks each) were tested in 20 hyperuricemic patients (SUA > 7.0mg/dL) with LV diastolicdysfunction in a double-blind, randomized crossover studydesign. Both febuxostatand benzbromaronesignificantly decreased SUA levels (-35% and -41%, respectively, both p Conclusions XO inhibition with febuxostatmight improve LV diastolic function, especially in patients with high SUA levels. This effect may be related to the decreased oxidative stress by febuxostat.