Efficacy and safety of urate-lowering therapies in asymptomatic hyperuricaemia: a systematic review and network meta-analysis of key clinical outcomes

Asymptomatic hyperuricaemia (AH) is an independent risk factor for chronic kidney disease, cardiovascular events, and metabolic disorders. However, controversies persist regarding the clinical use of urate-lowering therapies (ULTs). This study employs a network meta-analysis (NMA) to systematically evaluate the efficacy and safety of ULTs in AH across seven key endpoints: serum uric acid (SUA), estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hs-CRP), systolic blood pressure (SBP), major adverse cardiovascular events (MACE), composite renal events (CREs) and drug-induced liver injury (DILI). The findings aim to inform clinical decision-making. Four databases were systematically searched from their inception to March 2025 for all relevant literature, screening and evaluating randomized controlled trials (RCTs) assessing ULTs in AH. A frequentist NMA was conducted using R software. The Risk of Bias 2.0 tool was employed for bias assessment, and therapies were ranked <i>via</i> P-scores. In addition, transitivity assessment, network meta-regression, and sensitivity analysis were also performed. A total of 51 studies involving 8 ULTs and 10,281 subjects were included in this NMA. Random-effects modelling showed that, compared to controls, Verinurad_Febuxostat (P-score = 0.82; pooled mean difference [95% CI]: −3.20 [−4.76 to −1.64]) was the most effective in reducing SUA, Febuxostat (P-score = 0.78; 1.91 [0.47 to 3.35]) was the most effective in improving eGFR, Topiroxostat (P-score = 0.96; −6.10 [−11.75 to −0.45]) was most effective in improving SBP, and Febuxostat (P-score = 0.78; 0.77 [0.61 to 0.98]) reduced the risk of CREs most effectively. A None of the interventions showed significant differences in hs-CRP, MACE, or DILI. The Confidence in Network Meta-Analysis (CINeMA) assessment indicated that the overall quality of evidence was low to moderate. Available evidence suggests that febuxostat not only plays a significant role in lowering SUA levels but also significantly delays the decline in eGFR and reduces the risk of CREs.