Dataset Information

Comparison between the effects of allopurinol and febuxostat on the survival of patents on maintenance hemodialysis.

ABSTRACT:

Introduction

There were insufficient evidences regarding the effect of the two drugs (allopurinol and febuxostat) on patient survival in hemodialysis (HD) patients. Herein, we aimed to compare the efficacy of uric acid lowering drugs (ULDs) or the type of the drug on patient survival using a representative sample of maintenance HD patients in South Korea.

Methods

This study used a data from a national HD quality assessment program and the claims data. Use of ULDs was defined as more than one prescription during the 6 months of each HD quality assessment period. The patients were divided into three groups. Patients who were not prescribed allopurinol or febuxostat were included in Group 1 (n = 43,251); and patients who were prescribed allopurinol were included in Group 2 (n = 9,987); and patients who were prescribed febuxostat were included in Group 3 (n = 2,890).

Results

Kaplan-Meier curves showed that the survival rate was greatest in Group 3 and worst in Group 1 among the three groups. Multivariable analysis showed that Group 2 had better patient survival compared to Group 1; however, there was no significant difference in patient survival between Groups 2 and 3. In addition, patients with hyperuricemia or gout had better patient survival compared to those without these diseases.

Conclusions

Our study showed that survival in patients receiving ULDs was not inferior to those not receiving ULDs. Patient survival between patients on HD receiving allopurinol and those receiving febuxostat was similar.

SUBMITTER: Kang SH

PROVIDER: S-EPMC10308552 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparison between the Effects of Allopurinol and Febuxostat on the Survival of Patients on Maintenance Hemodialysis.

Kang Seok Hui SH Kim Bo Yeon BY Son Eun Jung EJ Kim Gui Ok GO Do Jun Young JY

American journal of nephrology 20230518 3-4

<h4>Introduction</h4>There were insufficient pieces of evidence regarding the effect of the two drugs (allopurinol and febuxostat) on patient survival in hemodialysis (HD) patients. Herein, we aimed to compare the efficacy of uric acid-lowering drugs (ULDs) or the type of the drug on patient survival using a representative sample of maintenance HD patients in South Korea.<h4>Methods</h4>This study used data from a national HD quality assessment program and the claims data. Use of ULDs was define ...[more]

PMID: 37231773

Similar Datasets

Project description:Rationale & objectiveAllopurinol and febuxostat, which are xanthine oxidoreductase inhibitors, have been widely used as uric acid-lowering medications. However, evidence regarding their cardiovascular effects in hemodialysis is insufficient. This study compared the effects of allopurinol and febuxostat on mortality and cardiovascular outcomes in patients receiving hemodialysis.Study designA retrospective observational cohort study.Setting & participantsData of 6,791 patients who had no history of topiroxostat usage and underwent maintenance hemodialysis between March 2016 and March 2019 at Yokohama Daiichi Hospital, Zenjinkai, and its affiliated dialysis clinics in Japan's Kanagawa and Tokyo metropolitan areas were collected.ExposureAllopurinol, febuxostat, and nontreatment.OutcomesAll-cause mortality, cardiovascular disease (CVD) events, heart failure (HF), acute myocardial infarction (AMI), and stroke.Analytical approachFor the main analyses, marginal structural Cox proportional hazards models were used to estimate HRs adjusted for time-varying confounding and selection bias because of censoring.ResultsAllopurinol and febuxostat showed significantly better survival than nontreatment for all-cause mortality (HR, 0.40; 95% CI, 0.30-0.54 and HR, 0.49; 95% CI, 0.38-0.63, respectively), without significant difference between allopurinol and febuxostat. Allopurinol showed significantly better survival than nontreatment, whereas febuxostat did not for CVD events (HR, 0.89; 95% CI, 0.84-0.95 and HR, 1.01; 95% CI, 0.96-1.07, respectively), HF (HR, 0.71; 95% CI, 0.56-0.90 and HR, 1.03; 95% CI, 0.87-1.21, respectively), and AMI (HR, 0.48; 95% CI, 0.25-0.91 and HR, 0.76; 95% CI, 0.49-1.19, respectively). No comparisons showed significant results for stroke.LimitationsThe ratio of renal or intestinal excretion of uric acid and uremic toxins could not be elucidated, and we could not investigate gene polymorphism because of the large number of cases.ConclusionsAllopurinol and febuxostat improved survival for all-cause mortality. Allopurinol and not febuxostat reduced the risk of CVD events, HF, and AMI.

Project description:BackgroundThe relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues.MethodsParticipants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events.ResultsThis study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P<0.001 for noninferiority). Overall, 80% of participants achieved mean target urates during phase 2 with no differences by treatment. There were no treatment differences (including cardiovascular events) in serious adverse events.ConclusionsAllopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; ClinicalTrials.gov identifier, NCT02579096.).

Project description:IntroductionGout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST).Methods and analysisFAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3.Ethics and disseminationFAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal.Trial registration numberFAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).

Project description:Background: Gout is a common disease and is usually treated with uric acid-lowering drugs (the most commonly used of which are febuxostat and allopurinol). However, the cardiovascular safety of febuxostat and allopurinol is still controversial. The purpose of our study is to evaluate the cardiovascular safety of the two drugs in patients with gout using one-stage and two-stage meta-analysis. Methods: PubMed, Embase, CBM, CNKI, WanFang, Central, and VIP were searched from inception to 30 January 2022. Randomized controlled trials which evaluated the cardiovascular safety of febuxostat or allopurinol for treating patients with gout were included. Based on the Kaplan-Meier curves of the two studies, individual patient data (IPD) were extracted and reconstructed. We used time-varying risk ratios (RRs) to summarize time-to-event outcomes, and the RRs of MACE incidence, cardiovascular mortality, and all-cause mortality were calculated by a multi-level flexible hazard regression model in 1-stage meta-analyses. p values were calculated using a log-rank test. At the same time, using the reconstructed IPD, we performed 2-stage meta-analyses to inform the quantitative estimates of time-specific relative risks at the six time points (1 , 2, 3, 4, 5, and 6 years) based on a random-effects model. Results: Two RCTs with 12,318 participants were included. In the incidence of major adverse cardiovascular events between the two regimens, there was no significant difference [RR = 0.99 (95% CI, 0.89-1.11), p = 0.87]; at the same time, there was no significant difference in cardiovascular mortality [RR = 1.17 (95% CI, 0.98-1.40),p = 0.08] or all-cause mortality [RR = 1.03 (95% CI, 0.91-1.17),p = 0.62]. In terms of 2-stage meta-analyses, there was no significant difference in any outcomes at any time point (moderate-to low-certainty evidence). Conclusion: In patients without atherosclerotic disease, febuxostat likely has a similar cardiovascular profile to allopurinol. However, in patients with a history of cardiovascular disease, allopurinol treatment is associated with less cardiovascular mortality as compared with febuxostat. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#loginpage, identifier PROSPERO, CRD42022325656.