Allopurinol therapy improves vascular endothelial function in subjects at risk for cardiovascular diseases: a meta‐analysis of randomized controlled trials

Wei, Xin; Mi, Shuhua; Lin, Zhiqin

doi:10.1111/1755-5922.12215

Cited by 41 publications

(30 citation statements)

References 51 publications

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“…They concluded that febuxostat improved endothelial dysfunction, but they used asymmetric dimethylarginine as the index of endothelial dysfunction. Concerning allopurinol, a meta‐analysis of 10 randomized controlled trials demonstrated that subjects treated with allopurinol exhibited a significantly greater improvement in FMD compared with controls . In the current study, there was no significant difference in the change in FMD by treatment between the febuxostat and allopurinol group.…”

Section: Discussioncontrasting

confidence: 58%

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

Hoshide

Kabutoya

Ueno

et al. 2019

J of Clinical Hypertension

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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.

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Section: Discussioncontrasting

confidence: 58%

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

Hoshide

Kabutoya

Ueno

et al. 2019

J of Clinical Hypertension

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“…31,32,33 On the other hand, its effect on endothelial dysfunction features prominently in some other studies and a few meta-analyses have been published to summarize these effects in a small number of RCTs that included patients labeled as at risk of cardiovascular disease. [34][35][36] All showed a statistically significant benefit of allopurinol therapy with mean increases in brachial artery flowmediated vasodilatation by respectively 2.50% (95% CI 0.15-4.84), 34 2.75% (95% CI 2.49-3.01), 35 and 1.67% (95% CI 0.83-2.50). 36 Two of these analyses also reported the effects on forearm blood flow in response to acetylcholine via VOP, with increases of respectively 68.80 (95% CI 18.70-118.90) 34 and 2.62 (95% CI 2.32-2.91).…”

Section: Discussionmentioning

confidence: 97%

“…[34][35][36] All showed a statistically significant benefit of allopurinol therapy with mean increases in brachial artery flowmediated vasodilatation by respectively 2.50% (95% CI 0.15-4.84), 34 2.75% (95% CI 2.49-3.01), 35 and 1.67% (95% CI 0.83-2.50). 36 Two of these analyses also reported the effects on forearm blood flow in response to acetylcholine via VOP, with increases of respectively 68.80 (95% CI 18.70-118.90) 34 and 2.62 (95% CI 2.32-2.91). 35 These metaanalyses included patients with different comorbidities and reached the conclusion that allopurinol has the potential to enhance endothelial function in general without specifying a specific patient population.…”

Section: Discussionmentioning

confidence: 97%

“…Few cohort studies have assessed its effect on cardiovascular events and mortality, and the results were inconsistent . On the other hand, its effect on endothelial dysfunction features prominently in some other studies and a few meta‐analyses have been published to summarize these effects in a small number of RCTs that included patients labeled as at risk of cardiovascular disease . All showed a statistically significant benefit of allopurinol therapy with mean increases in brachial artery flow‐mediated vasodilatation by respectively 2.50% (95% CI 0.15‐4.84), 2.75% (95% CI 2.49‐3.01), and 1.67% (95% CI 0.83‐2.50) .…”

Section: Discussionmentioning

confidence: 99%

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Allopurinol and endothelial function: A systematic review with meta‐analysis of randomized controlled trials

Alem

2018

Cardiovascular Therapeutics

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SummaryAimOxidative stress and endothelial dysfunction are two inter‐related conditions commonly seen in patients with cardiovascular risk factors. The enzyme, xanthine oxidase, is an important contributor to these phenomena but to a variable degree in different patient populations. This meta‐analysis will summarize the effect of allopurinol, an established xanthine oxidase inhibitor, on endothelial function among patients with different comorbidities.MethodsMedline Complete, PubMed, ProQuest, ClinicalKey, Wiley Online Library, and Cochrane Central Register of Controlled Trials were searched till July 29, 2017. Meta‐analysis was planned for randomized controlled trials (RCTs) that investigated allopurinol effects on endothelial function. A random effect model was used to calculate the standardized mean difference (with 95% confidence intervals: CI) as an estimate of effect size. Heterogeneity was quantified by four types of information: Q statistics, I 2 statistic, Tau‐squared (T 2), and Tau (T).ResultsThirty eligible studies were identified; 12 were included in the final analysis and subdivided among 3 patient’s groups: patients with chronic heart failure (CHF; 197 patients), patients with chronic kidney disease (CKD; 183 patients), and patients with type 2 diabetes mellitus (DM; 170 patients). Allopurinol was found to have a statistically significant benefit on endothelial function in patients with CHF and CKD but not in type 2 DM. The standardized mean differences and CI in the three patient’s groups were 0.776 (0.429, 1.122), 0.350 (0.009, 0.690), and 1.331 (−0.781, 3.444), respectively.ConclusionAllopurinol has an antioxidant property that might partially reverse endothelial dysfunction in patients with certain comorbidities. The importance of this property and the magnitude of the beneficial effect are likely to be related to the relative contribution of xanthine oxidase into the oxidative stress associated with different underlying pathologies.

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“…Most internists stated that AHU treatment is effective and confirmed the need to reach a goal treatment for SUA levels <6 mg/dL. Allopurinol remains the firstline approach to AHU treatment, 28 although 50% of internists consider it useful treating AHU with febuxostat. Febuxostat can be used in patients with mild-tomoderate renal or hepatic involvement, which is frequently observed in internal medicine patients.…”

Section: Discussionmentioning

confidence: 99%

Self-reported hypertension, dyslipidemia and hyperuricemia management by Italian Internal Medicine Units: a national survey of the FADOI Study Group in Cardiovascular Medicine

Mazza¹,

Lenti²,

D'Avino

et al. 2017

Ital J Med

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The aim of this study was to evaluate the management practices of internal medicine clinicians for patients with cardiovascular risk factors, with particular respect to treatment thresholds, medication choices and target goals. A sample of internists - representatives of Internal Medicine Units (IMUs) from all the regions in Italy - were identified by the cardiovascular medicine study group of the Italian Internal Medicine FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti) Society and invited to fill out a questionnaire about hypertension, dyslipidemia and hyperuricemia. From the 101 questionnaires collected, it was found that despite large heterogeneity between IMUs in terms of patient management and adherence to guidelines, internists were experts in the management of patients with multiple cardiovascular risk factors and associated comorbidities. We hope that these data prompt the internal medicine community to consider the value of producing shared, real-world guidelines on the management of cardiovascular disease.

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Allopurinol therapy improves vascular endothelial function in subjects at risk for cardiovascular diseases: a meta‐analysis of randomized controlled trials

Abstract: Allopurinol therapy is associated with significantly improved endothelial function in subjects at risk of CVD risks, and the beneficial effects of allopurinol seemed to be more remarkable in patients with normal UA at baseline.

Cited by 41 publications

References 51 publications

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

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

Allopurinol and endothelial function: A systematic review with meta‐analysis of randomized controlled trials

Self-reported hypertension, dyslipidemia and hyperuricemia management by Italian Internal Medicine Units: a national survey of the FADOI Study Group in Cardiovascular Medicine

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