Effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein, an oxidative stress marker: A subanalysis of the PRIZE study.

ABSTRACT

BACKGROUND: Febuxostat is a selective xanthine oxidase inhibitor that reportedly exhibits antioxidant properties. We previously performed a multicentre, randomized controlled (PRIZE) study for vascular evaluation under uric acid (UA) control by febuxostat to investigate the progression of carotid lesions in asymptomatic hyperuricemic patients with carotid atherosclerosis for 2 years. HYPOTHESIS: The current subanalysis of the PRIZE study aimed to assess the effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker. METHODS: We recruited 383 patients (febuxostat group, n = 200; control group, n = 183) from the PRIZE trial for whom MDA-LDL measurements were available. The UA, MDA-LDL, low-density lipoprotein cholesterol (LDL-C) levels, and MDA-LDL/LDL-C ratio were identified, represented as the estimated difference from baseline to 24 months. We also evaluated the relationship between febuxostat dose (10, ≤20 to <40, and ≤40 to ≤60 mg) and changes in the MDA-LDL level, LDL-C level, or MDA-LDL/LDL-C ratios. RESULTS: The estimated change in MDA-LDL/LDL-C ratio from baseline to 24 months was significantly lower in the febuxostat group than in the control group (p = .025), whereas the estimated changes in MDA-LDL (p = .235) and LDL-C (p = .323) levels did not differ between the two groups. No significant correlation existed between the febuxostat doses and the estimated change in the MDA-LDL level (p = .626), LDL-C level (p = .896), or MDA-LDL/LDL-C ratio (p = .747). CONCLUSIONS: Our findings may indicate a possibility that febuxostat can lower the MDA-LDL/LDL-C ratio, a potential marker of atherosclerosis and oxidative stress, in asymptomatic hyperuricemic patients with carotid atherosclerosis. Further studies are required to validate our findings and elucidate the clinical antioxidant effect of febuxostat.