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Class effect of xanthine oxidase inhibitors on flow-mediated dilatation in hypertensive patients: A randomized controlled trial.

ABSTRACT: A direct comparison of the effects of febuxostat and allopurinol on flow-mediated dilatation (FMD) will help to clarify which agent provides a better reduction of cardiovascular risk in hypertensive patients. Hypertensive patients with hyperuricemia were randomized into a febuxostat (10-40 mg, n = 33) or allopurinol (100-200 mg, n = 31) group and followed up for 6 months. Both the febuxostat (7.9 ± 1.3 mg/dL vs 5.6 ± 1.0 mg/dL, P < .001) and allopurinol (8.2 ± 1.3 mg/dL vs 6.1 ± 1.0 mg/dL, P < .001) groups exhibited significant reductions in uric acid after treatment. There was no significant difference in the change in FMD between the two treatment groups (0.6 ± 2.6% vs 0.2 ± 2.3%, P = .504). However, stratified analysis showed that febuxostat achieved a significantly greater change in FMD compared to allopurinol in the elderly group (1.3 ± 2.9% vs -0.7%±1.8%, P = .047). There was no difference in the improvement of FMD between febuxostat and allopurinol, but febuxostat may provide an improvement of FMD in elderly people.

SUBMITTER: Hoshide S

PROVIDER: S-EPMC8029901 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Class effect of xanthine oxidase inhibitors on flow-mediated dilatation in hypertensive patients: A randomized controlled trial.

Hoshide Satoshi S Kabutoya Tomoyuki T Ueno Hiromi H Kario Kazuomi K

Journal of clinical hypertension (Greenwich, Conn.) 20191224 3

A direct comparison of the effects of febuxostat and allopurinol on flow-mediated dilatation (FMD) will help to clarify which agent provides a better reduction of cardiovascular risk in hypertensive patients. Hypertensive patients with hyperuricemia were randomized into a febuxostat (10-40 mg, n = 33) or allopurinol (100-200 mg, n = 31) group and followed up for 6 months. Both the febuxostat (7.9 ± 1.3 mg/dL vs 5.6 ± 1.0 mg/dL, P < .001) and allopurinol (8.2 ± 1.3 mg/dL vs 6.1 ± 1.0 mg/dL, P < . ...[more]

PMID: 31873985

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Project description:BackgroundXanthine oxidase inhibitors (XOI), classified as purine-like (allopurinol and oxypurinol) and non-purine (febuxostat and topiroxostat) XOI, present antioxidant properties by reducing the production of reactive oxygen species derived from purine metabolism. Oxidative stress is an important factor related to endothelial dysfunction and ischemia-reperfusion injury, and may be implicated in the pathogenesis of heart failure, hypertension, and ischemic heart disease. However, there is contradictory evidence regarding the possible cardiovascular (CV) protective effect exerted by XOI. Our objective is to compare the incidence of major adverse cardiovascular events (MACE), mortality, total (TCE) and specific CV events in randomized controlled trials (RCTs) testing XOI against placebo or no treatment.MethodsPubMed, EMBASE, Web of Science, Cochrane Central, Lilacs databases were searched from inception to Dec 30 2016, along with hand searching. RCTs including exclusively adult individuals, lasting ≥ 4 weeks, with no language restriction, were eligible. Independent paired researchers selected studies and extracted data. Considering the expected rarity of events, Peto and DerSimonian/Laird odds ratios (OR), the latter in case of heterogeneity, were used for analysis. Random-effects meta-regression was used to explore heterogeneity.ResultsThe analysis of MACE included 81 articles (10,684 patients, 6434 patient-years). XOI did not significantly reduce risk of MACE (ORP = 0.71, 95% CI 0.46-1.09) and death (0.89, 0.59-1.33), but reduced risk of TCE (0.60, 0.44-0.82; serious TCE: 0.64, 0.46 to 0.89), and hypertension (0.54, 0.37 to 0.80). There was protection for MACE in patients with previous ischemic events (0.42, 0.23-0.76). Allopurinol protected for myocardial infarction (0.38, 0.17-0.83), hypertension (0.32, 0.18-0.58), TCE (0.48, 0.31 to 0.75, I2 = 55%) and serious TCE (0.56, 0.36 to 0.86, I2 = 44%). Meta-regression associated increasing dose of allopurinol with higher risk of TCE and serious TCE (P < 0.05). Accordingly, lower doses (≤ 300 mg/day) of allopurinol reduced the risk of TCE, unlike higher doses. Non-purine-like XOI did not significantly reduce or increase the risk of adverse CV events, but confidence intervals were wide. Quality of evidence was generally low to moderate.ConclusionsPurine-like XOI may reduce the incidence of adverse CV outcomes. However, higher doses of allopurinol (> 300 mg/day) may be associated with loss of CV protection.

Dataset Information

Class effect of xanthine oxidase inhibitors on flow-mediated dilatation in hypertensive patients: A randomized controlled trial.

Publications

Class effect of xanthine oxidase inhibitors on flow-mediated dilatation in hypertensive patients: A randomized controlled trial.

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