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Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia.

ABSTRACT: Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open-label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40-160 mg/day or febuxostat 10-60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio-ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (-2.9 and -2.5 mg/dl; both p < 0.001) and morning home systolic BP (-3.6 and -5.1 mm Hg; both p < 0.01) after 24 weeks' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin-creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (-20.8%; p = 0.021), but not febuxostat (-8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks' treatment.

SUBMITTER: Kario K

PROVIDER: S-EPMC8029836 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia.

Kario Kazuomi K Nishizawa Masafumi M Kiuchi Mari M Kiyosue Arihiro A Tomita Fumishi F Ohtani Hiroshi H Abe Yasuhisa Y Kuga Hideyo H Miyazaki Satoshi S Kasai Takatoshi T Hongou Makiko M Yasu Takanori T Kuramochi Jin J Fukumoto Yoshihiro Y Hoshide Satoshi S Hisatome Ichiro I

Journal of clinical hypertension (Greenwich, Conn.) 20210105 2

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open-label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40-160 mg/day ...[more]

PMID: 33400348

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Project description:BackgroundHigh blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a link between hyperuricemia and hypertension. Hyperuricemia affects 25% to 40 % of individuals with untreated hypertension; a much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (UA) might lower blood pressure (BP) is an unanswered question.ObjectivesTo determine whether UA-lowering agents reduce BP in patients with primary hypertension or prehypertension compared with placebo.Search methodsThe Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS up to March 2016 and contacted authors of relevant papers regarding further published and unpublished work.Selection criteriaTo be included in this review, the studies had to meet the following criteria: 1) randomized or quasi-randomized, with a group assigned to receive a UA-lowering agent and another group assigned to receive placebo; 2) double-blind, single-blind or open-label; 3) parallel or cross-over trial; 4) cross-over trials had to have a washout period of at least two weeks; 5) minimum treatment duration of four weeks; 6) participants had to have a diagnosis of essential hypertension or prehypertension, and hyperuricemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men and 5.5 mg/dL in children/adolescents); 7) outcome measures assessed included change in clinic systolic, diastolic or 24-hour ambulatory BP.Data collection and analysisThe two review authors independently collected the data using a data extraction form, and resolved any disagreements via discussion. We assessed risk of bias using the Cochrane Collaboration' Risk of bias' tool.Main resultsIn this review update, we examined the abstracts of 349 identified papers and selected 21 for evaluation. We also identified three ongoing studies, the results of which are not yet available. Three other randomized controlled trials (RCTs) (two new), enrolling individuals with hypertension or prehypertension, and hyperuricemia, met the inclusion criteria for the review and were included in the meta-analysis. Low quality of evidence from three RCTs indicate no reduction in systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic (-3.9 mmHg, 95% CI -9.2 to 1.4) 24-hour ambulatory BP with UA-lowering drugs compared with placebo. Low quality of evidence from two RCTs reveal a reduction of systolic clinic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but not diastolic clinic BP (-6.45 mmHg, 95% CI -13.60 to 0.70). High quality of evidence from three RCTs indicates that serum UA levels were reduced by 3.1 mg/dL (95% CI 2.4 to 3.8) in the participants that received UA-lowering drugs. Very low quality of evidence from three RCTs suggests that withdrawals due to adverse effects were not increased with UA-lowering therapy (RR 1.86, 95% CI 0.43 to 8.10).Authors' conclusionsIn this updated systematic review, the RCT data available at present are insufficient to know whether UA-lowering therapy also lowers BP. More studies are needed.

Dataset Information

Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia.

Publications

Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia.

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