Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia.
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SUBMITTER: Kario K
PROVIDER: S-EPMC8029836 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hyperuricemia is reported to be related to rapid progression of renal function in patients with chronic kidney disease (CKD). Allopurinol, a uric acid lowering agent, protects renal progression. However, it is not widely used in patients with CKD because of its serious adverse event. Febuxostat can be alternatively used for patients who are intolerable to allopurinol. We aimed to determine renoprotective effect and urate-lowering effect between the two drugs.We performed a systematic review and meta-analysis of randomized controlled trials to assess the effects of febuxostat compared to allopurinol in patients with hyperuricemia. MEDLINE, Embase, and Cochrane Library databases were searched to identify research publications.Four relevant publications were selected from among 3,815 studies. No significant differences were found in the changes in serum creatinine from baseline between the febuxostat and allopurinol groups. Changes in estimated glomerular filtration rate (eGFR) were observed between the two groups at 1 month (mean difference 1.65 mL/min/1.73 m2, 95% confidence interval [CI] 0.38, 2.91 mL/min/1.73 m2; heterogeneity ?2 = 1.25, I2 = 0%, P = 0.01); however, the changes in eGFR were not significantly different at 3 months. A significant difference did exist in the changes in albuminuria levels from baseline between the febuxostat and allopurinol groups (mean difference -80.47 mg/gCr, 95% CI -149.29, -11.64 mg/gCr; heterogeneity ?2 = 0.81, I2 = 0%, P = 0.02). A significant difference was also observed in the changes in serum uric acid from baseline between the febuxostat and allopurinol groups (mean difference -0.92 mg/dL, 95% CI -1.29, -0.56 mg/dL; heterogeneity ?2 = 6.24, I2 = 52%, P < 0.001).Febuxostat might be more renoprotective than allopurinol.
| S-EPMC5592895 | biostudies-other
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.
| S-EPMC6478066 | biostudies-literature
Project description:Previous epidemiological studies have suggested that uric acid is an independent risk factor for incident hypertension, whereas few studies have evaluated the effect of hyperuricemia on blood pressure control in hypertensive patients. We investigated whether hyperuricemia predicts uncontrolled hypertension through a large-scale prospective cohort study with hypertensive patients treated with fimasartan in the Republic of Korea (the Kanarb-Metabolic Syndrome study).Of the 10,601 hypertensive patients who were recruited from 582 private clinics and 11 university hospitals at baseline, 7725 completed the follow-up after 3 months of fimasartan medication, and 6506 were included in the analysis after excluding those with missing values. We estimated the risk of uncontrolled hypertension after 3 months (?130/80 mm Hg in those with diabetes or chronic renal failure and ?140/90 mm Hg in the remaining patients) related with baseline hyperuricemia (serum uric acid ?7?mg/dL in males ?6?mg/dL in females) using multiple logistic regression models.Hyperuricemia increased the risk of uncontrolled hypertension after 3 months of fimasartan medication (odds ratio, 1.247; 95% confidence interval, 1.063-1.462). Males in the highest quartile of uric acid level were at a 1.322 (95% confidence interval, 1.053-1.660) times higher risk of uncontrolled hypertension in reference to the lowest quartile; the same analyses in females were not significant. Patients without metabolic syndrome had significantly higher odds of uncontrolled hypertension with hyperuricemia (odds ratio, 1.328; 95% confidence interval, 1.007-1.751).Hyperuricemia predicted uncontrolled hypertension even after 3 months of fimasartan treatment in hypertensive patients.
| S-EPMC4956806 | biostudies-other
Project description:BackgroundThe benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol.Methods and resultsThe prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e') decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2'-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group.ConclusionsCompared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients.
| S-EPMC8789120 | biostudies-literature
Project description:The aim of this study was to assess the prognostic value of hyperuricemia in patients with established hypertension by systematic review and meta-analysis of cohort studies. MEDLINE, Embase, and the Chinese Biomedical Literature Database were searched through January 2015. Seventeen cohort studies were included and their methodological quality was moderate to high, with Newcastle-Ottawa Scale scores ranging from 6 to 9. Random-effects model meta-analyses showed that in terms of adjusted categorical data, hyperuricemia significantly correlated with cardiovascular diseases in hypertensive patients (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.13-2.03), all-cause mortality (HR, 1.12; 95%CI, 1.02-1.23), and diabetes (HR, 1.84; 95% CI, 1.02-3.30) but not with stroke (HR, 0.85; 95%CI, 0.57-1.27); while, in terms of adjusted continuous data, the corresponding pooled HRs were 1.17 (95% CI, 1.07-1.27), 1.05 (95% CI, 0.98-1.13), 1.28 (95% CI, 1.18-1.38), and 1.06 (95% CI, 0.98-1.16), respectively. The findings of our meta-analysis suggest that hyperuricemia could slightly increase the risk of cardiovascular diseases and diabetes in patients with hypertension.
| S-EPMC8031654 | biostudies-literature
Project description:BackgroundPrior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients.MethodsOur study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups.ResultsMultivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings.ConclusionThis study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.
| S-EPMC11319118 | biostudies-literature
Project description:Elevated serum uric acid (UA) level has been shown to be influenced by multiple genetic variants, but it remains uncertain how UA-associated variants differ in their influence on hyperuricemia risk in people taking antihypertensive drugs. We examined a total of 43 UA-related variants at 29 genes in 1840 patients with hypertension from a community-based longitudinal cohort during a median 2.25-year follow-up (including 1031 participants with normal UA, 440 prevalent hyperuricemia at baseline, and 369 new-onset hyperuricemia). Compared with the wild-type genotypes, patients carrying the SLC2A9 rs3775948G allele or the rs13129697G allele had decreased risk of hyperuricemia, while patients carrying the SLC2A9 rs11722228T allele had increased risk of hyperuricemia, after adjustment for cardiovascular risk factors and correction for multiple comparisons; moreover, these associations were modified by the use of diuretics, β-blockers, or angiotensin converting enzyme inhibitors. The rs10821905A allele of A1CF gene was associated with increased risk of hyperuricemia, and this risk was enhanced by diuretics use. The studied variants were not observed to confer risk for incident cardiovascular events during the follow-up. In conclusion, the genes SLC2A9 and A1CF may serve as potential genetic markers for hyperuricemia risk in relation to antihypertensive drugs therapy in Chinese hypertensive patients.
| S-EPMC9306909 | biostudies-literature
Project description:Chronic stress is closely linked to the metabolic syndrome, diabetes, hyperuricemia and thromboembolism, but the mechanisms remain elusive. We reported recently that stress targets visceral adipose tissue (VAT), inducing lipolysis, low-grade inflammation with production of inflammatory adipokines, metabolic derangements such as insulin resistance, and prothrombotic state. In the present study, we hypothesized the involvement of VAT xanthine oxidoreductase (XOR), a source of reactive oxygen species (ROS) and uric acid (UA) in the above processes. Restraint stress in mice resulted in upregulation of XOR and xanthine oxidase activity, accumulation of ROS in VAT as well as liver and intestine, increase in serum UA levels, upregulation of NADPH oxidase subunits and downregulation of antioxidant enzymes. Immunohistochemistry and RT-PCR analysis also showed that restraint stress induced VAT monocyte accumulation and proinflammatory adipokine production, resulting in reduced insulin sensitivity and induction of plasminogen activator inhibitor-1 and tissue factor in VAT. Treatment with febuxostat, a potent XO inhibitor, suppressed stress-induced ROS production and VAT inflammation, resulting in improvement of serum UA levels, insulin sensitivity, and prothrombotic tendency. Our results suggest that stress perturbs glucose and UA metabolism, and promotes prothrombotic status, and that XO inhibition by febuxostat might be a potential therapy for stress-related disorders.
| S-EPMC5430858 | biostudies-literature
Project description:ContextCombining a sodium-glucose cotransporter 2 inhibitor with a xanthine oxidase inhibitor (XOI) and a urate transporter 1 (URAT1) inhibitor may enhance serum uric acid (sUA) lowering. However, concerns exist regarding high urinary UA (uUA) excretion rates and subsequent crystallization in renal tubules.ObjectiveTo assess whether dapagliflozin added to verinurad, a selective URAT1 inhibitor, and febuxostat, an XOI, increases uUA excretion.DesignRandomized, placebo-controlled, 2-way crossover study (NCT03316131).PatientsAdults with asymptomatic hyperuricemia.InterventionsSubjects (N = 36) were randomized to oral once-daily 9 mg verinurad plus 80 mg febuxostat plus 10 mg dapagliflozin for 7 days and 7 days of oral once-daily 9 mg verinurad plus 80 mg febuxostat plus placebo with an intervening 7- to 21-day washout period.Main outcome measureDifference in peak uUA excretion between groups from baseline to day 7. Secondary outcomes included changes in sUA levels and 24-h uUA excretion.ResultsBoth regimens lowered mean peak uUA excretion (least squares mean changes from baseline: -12.9 mg/h [95% confidence interval (CI): -21.0 to -4.7], dapagliflozin; -13.2 mg/h [95% CI -21.3 to -5.0], placebo). sUA concentrations were lower with dapagliflozin (mean treatment difference -62.3 µmol/L [95% CI -82.8 to -41.8]). Dapagliflozin did not impact verinurad pharmacokinetics, its main metabolites, or febuxostat or fasting plasma glucose levels vs verinurad plus febuxostat. There were no clinically relevant changes in safety parameters.ConclusionsDapagliflozin further reduced sUA without influencing uUA excretion, suggesting that its combination with verinurad and febuxostat at the doses tested does not adversely affect kidney function.Clinical trial registration numberNCT03316131.
| S-EPMC8063233 | biostudies-literature
Project description:BackgroundWhile xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia.MethodsA prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12.ResultsFewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41-0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62-0.89, P = 0.001) were independently associated with lower rates of achieving SU target.ConclusionsPeople with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.
| S-EPMC10712161 | biostudies-literature