Long-term treatment with the xanthine oxidase inhibitor febuxostat may provide beneficial effects on arterial stiffness but not on carotid atherosclerosis, according to results of an analysis published in the journal Hypertension Research.

A subanalysis of the multicenter, prospective, randomized, open-label, blinded-endpoint Program of Vascular Evaluation Under Uric Acid Control by the Xanthine Oxidase Inhibitor Febuxostat (PRIZE) study was conducted. Recognizing that atherosclerosis and arterial stiffness reflect different facets of atherosclerotic vascular damage, the researchers sought to compare the long-term effects of febuxostat on atherosclerosis and arterial stiffness among a cohort of Japanese patients. All participants were randomly assigned to either a febuxostat group or a control group. The febuxostat group received 10-60 mg of febuxostat daily and the control group received a nonpharmacologic treatment for hyperuricemia. Carotid ultrasonography and evaluation of arterial stiffness were performed at each of the clinical sites at baseline, after 12 months, and after 24 months or at premature termination.

Study eligibility criteria included being aged 20 years or older with asymptomatic hyperuricemia (ie, a serum uric acid level of >7.0 mg/dL) and a maximum common carotid artery intima-media thickness of 1.1 mm or thicker. Following exclusion for several different reasons, 52 participants in the febuxostat arm and 48 participants in the control arm were enrolled in the subanalysis.


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Blood pressure was measured in-office with the use of either auscultation or oscillometry, with hypertension defined based on guidelines issued by the Japanese Society of Hypertension. All patients in both groups underwent lifestyle modifications for hyperuricemia, including a healthy diet and exercise, with the modifications persisting throughout the study.

The primary study endpoint was the percentage of change in parameters of arterial stiffness (ie, brachial-ankle pulse wave velocity [baPWV] or cardio-ankle vascular index [CAVI]). An additional study endpoint was the percentage change in mean intima-media thickness of the carotid artery from baseline to 24 months.

The results of the study showed that although the reduction in serum uric acid was greater in the febuxostat arm than in the control arm, the adjusted percentage decrease in arterial stiffness parameters at 24 months was significantly greater in the febuxostat group compared with the control group (mean between-group difference with febuxostat minus control, -5.099%; 95% CI, -10.009% to -0.188%; P =.042).

Limitations of the current subanalysis include the small number of participants. Further, since arterial stiffness was evaluated by only 2 parameters (baPWV or CAVI) an assessment of absolute changes in arterial stiffness was not possible.

The researchers wrote, “Long-term treatment with febuxostat may provide beneficial effects on arterial stiffness but not on carotid atherosclerosis. A long-term study to examine the effect of febuxostat on cardiovascular outcomes related to increased arterial stiffness is warranted. “

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference  

Shiina K, Tomiyama H, Tanaka A, et al; PRIZE Study Investigators. Differential effect of a xanthine oxidase inhibitor on arterial stiffness and carotid atherosclerosis: a subanalysis of the PRIZE study. Hypertens Res. Published online February 15, 2022. doi:10.1038/s41440-022-00857-9