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. 2022 Jun 23;23(1):223.
doi: 10.1186/s12882-022-02850-3.

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

Tunlanut Sapankaew  1 , Kunlawat Thadanipon  1 , Narisa Ruenroengbun  1   2 , Kamolpat Chaiyakittisopon  1   2 , Atiporn Ingsathit  1 , Pawin Numthavaj  3 , Nathorn Chaiyakunapruk  4 , Gareth McKay  5 , John Attia  6 , Ammarin Thakkinstian  1
Affiliations

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

Tunlanut Sapankaew et al. BMC Nephrol. .

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 12th November 2019.

Keywords: Cardiovascular events; Chronic kidney disease; Hyperuricemia; Network meta-analysis; Systematic review; Treatment.

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Conflict of interest statement

All authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of study selection
See this image and copyright information in PMC

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