Effect of febuxostat on left ventricular diastolic function in patients with asymptomatic hyperuricemia: a sub analysis of the PRIZE Study

Abstract

Hyperuricemia is related to an increased risk of cardiovascular events from a meta-analysis and antihyperuricemia agents may influence to cardiac function. We evaluated the effect of febuxostat on echocardiographic parameters of diastolic function in patients with asymptomatic hyperuricemia as a prespecified endpoint in the subanalysis of the PRIZE study. Patients in the PRIZE study were assigned randomly to either add-on febuxostat treatment group or control group with only appropriate lifestyle modification. Of the 514 patients in the overall study, 65 patients (31 in the febuxostat group and 34 in the control group) who had complete follow-up echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included. The primary endpoint was a comparison of the changes in the E/e′ between the two groups from baseline to 24 months. Interestingly, e′ was slightly decreased in the control group compared with in the febuxostat group (treatment p = 0.068, time, p = 0.337, treatment × Time, p = 0.217). As a result, there were significant increases in E/e′ (treatment p = 0.045, time, p = 0.177, treatment × time, p = 0.137) after 24 months in the control group compared with the febuxostat group. There was no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive troponin I between the two groups during the study period. In conclusions, additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have a potential of preventable effects on the impaired diastolic dysfunction.

Impact of febuxostat on visit-to-visit blood pressure variability: insights from the randomised PRIZE Study

“…The detailed study protocol and design are described in previous publications. [12][13][14][15][16] Briefly, patients with hyperuricemia (serum uric acid (SUA) level>7.0 mg/dL) and carotid plaques (maximum IMT of the common carotid artery≥1.1 mm) at screening were enrolled. Major exclusion criteria included uric acid lowering medications within 8 weeks prior to assessment of eligibility and gouty tophus or symptoms of gout arthritis within 1 year.…”

“…This is a subanalysis of the PRIZE Study, a multicentre, prospective, randomised, open-label, blinded-endpoint trial to assess a hypothesis if febuxostat delays carotid intima–media thickness (IMT) progression in patients with hyperuricemia. The detailed study protocol and design are described in previous publications 12–16. Briefly, patients with hyperuricemia (serum uric acid (SUA) level>7.0 mg/dL) and carotid plaques (maximum IMT of the common carotid artery≥1.1 mm) at screening were enrolled.…”

Impact of Hyperuricemia and Urate-Lowering Agents on Cardiovascular Diseases

“… 64 Nonetheless, further sub-analysis showed that the use of febuxostat was associated with better diastolic function and decreased arterial stiffness. 60 , 65 , 66 …”

Update on Hypertension Research in 2021

“…Furuhashi et al reported that plasma xanthine oxidoreductase (XOR) activity was associated with hypertension in 271 nondiabetic subjects in the Tanno–Sobetsu Study [ 192 ]. Kusunose et al reported that additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have potential prevention effects on impaired diastolic dysfunction in the subanalysis of the PRIZE study [ 193 ]. These reports suggested the potential direct antioxidant effects of the treatment as reflected in serum uric acid levels as well as its xanthine-oxidase-lowering properties in tissue [Supplementary Information 11 - 3 ].…”