Dataset Information

Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials.

ABSTRACT:

Background

Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.

Methods

MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events.

Results

NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m², 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m², 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified.

Conclusions

Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function.

Trial registration

This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12^th November 2019.

SUBMITTER: Sapankaew T

PROVIDER: S-EPMC9229855 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials.

Sapankaew Tunlanut T Thadanipon Kunlawat K Ruenroengbun Narisa N Chaiyakittisopon Kamolpat K Ingsathit Atiporn A Numthavaj Pawin P Chaiyakunapruk Nathorn N McKay Gareth G Attia John J Thakkinstian Ammarin A

BMC nephrology 20220623 1

<h4>Background</h4>Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.<h4>Methods</h4>MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asy ...[more]

PMID: 35739495

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Project description:BackgroundContradictory evidence exists for association of hyperuricemia and kidney function. To investigate the association of hyperuricemia and kidney function decline (hyperuricemia question) and effect of urate-lowering therapies (ULTs) on kidney function (ULT question), we performed a systematic review and meta-analysis.MethodsMEDLINE, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to July 2020. We selected observational studies for the hyperuricemia question and controlled trials for the ULT question. Two investigators independently assessed study eligibility and abstracted the data. Risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Meta-analysis was done using the inverse variance method and random effect model. We estimated odds ratio (OR), hazard ratio (HR), risk ratio (RR), and the mean difference (MD). Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsOf 12,037 studies screened, 131 studies with 3,414,226 patients were included. Hyperuricemia was associated with a significant risk of rapid estimated glomerula filtration rate (eGFR) decline ⩾3 ml/min per 1.73 m2 per year (OR 1.38, 95% CI 1.20-1.59; low certainty), albuminuria (OR/HR 1.94, 95% CI 1.34-2.79; very low certainty), chronic kidney disease (OR/HR 2.13, 95% CI 1.74-2.61; very low certainty), and kidney failure (HR 1.53, 95% CI 1.18-1.99; very low certainty). Compared with control, ULT use for ⩾1 year was associated with significantly more improved eGFR (MD 1.81 ml/min per 1.73 m2, 95% CI 0.26-3.35; very low certainty), serum creatinine (MD -0.33 mg/dl, 95% CI -0.47 to -0.19; low certainty), and proteinuria (MD -5.44 mg/day, 95% CI -8.49 to -2.39; low certainty), but no difference in kidney failure.ConclusionHyperuricemia is associated with worsening eGFR, albuminuria, chronic kidney disease, and kidney failure. ULT use for ⩾1 year may improve kidney function.RegistrationThe protocol was registered at PROSPERO database, CRD42015013859.

Project description:BackgroundThe comparative efficacy and safety of PCSK9 inhibitors, statins, and ezetimibe to lower lipid levels in patients with hypercholesterolemia remain unknown. We aimed to investigate the benefits and harms of the lipid-lowering agents in these patients.MethodsPubMed, Embase, and the Cochrane Library were searched from January 1, 2000 to June 1, 2018 for relevant randomized controlled trials (RCTs). Frequentist network meta-analysis was used to pool all estimates. Ranking probabilities were used to rank the comparative effects of all drugs against placebo.ResultsEighty-four RCTs enrolled 246,706 patients were included. Most of the included were assessed as low risk of bias. The probabilities of PCSK9 inhibitors that ranked first in improving lipid outcomes were all 100%. The probability of statins that ranked first in reducing the risk of cardiovascular (CV) events was 60.6%, and the probability of PCSK9 inhibitor was 37.1%, while no significant difference of efficacy in reducing CV events was observed between the 2 agents (odds ratios [OR] 0.98, 95% CI 0.87-1.11). Statin ranked first in reducing all-cause and CV death. Compared with placebo, statins were associated with reduced risks of all-cause (OR 0.90, 95% CI 0.85-0.96) and CV death (OR 0.83, 95% CI 0.75-0.91) while PCSK9 inhibitors and ezetimibe were not. No agents caused adverse events (including neurocognitive events), except that statins therapy significantly increases the levels of alanine aminotransferase (ALT) (OR 1.89, 95% CI 1.42-2.51) and creatine kinase (CK) (OR 1.45, 95% CI 1.09-1.93) and the incidence of diabetes (OR 1.13, 95% CI 1.02-1.26).ConclusionsPCSK9 inhibitors were the most effective lipid-lowering agents in improving lipid levels. Furthermore, PCSK9 inhibitors achieved similar CV benefits like statins, while PCSK9 inhibitors were not associated with any increased risk of statin-related side-effects. Thus, PCSK9 inhibitors may also be recommended as promisingly first-line lipid-lowering treatment for patients with hypercholesterolemia, especially for these with statins intolerance or resistance.

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Dataset Information

Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials.

Background

Methods

Results

Conclusions

Trial registration

Publications

Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials.

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