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 12th November 2019.

The relation between uric acid level and blood pressure values among patients hospitalized in a department of internal medicine

“…Respecting the evaluation of uric acid-lowering treatment and its relation to BP, allopurinol dose was not a factor independently associated with BP in the group of patients without anti-hypertensive drug intake in our study. This is consistent with multiple studies [ 18 – 21 ]. Some meta-analyses regarding this subject conclude the evidence is insufficient to unequivocally confirm the hypotensive effect of uric acid-lowering agents in hypertensive patients [ 25 ].…”

Uric Acid and Chronic Kidney Disease: Still More to Do

“…One might hope that meta-analyses might help resolve the issues, but even here there remains confusion, because some recent studies suggest that treatment of asymptomatic hyperuricemia in CKD does slow progression, 52 , 53 whereas others are mixed or indeterminant, 50 , 54 , 55 and some are negative. 56 Some meta-analyses show benefit with only specific urate-lowering drugs, such as febuxostat.…”

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation

“…A recent network meta-analysis including 23 double-blind, placebo-controlled, randomized clinical trials carried out with different SUA lowering drugs concluded that allopurinol and febuxostat had significantly lower composite renal events (deterioration of renal function, end-stage renal disease, and initiation of renal replacement therapy) than placebo (Relative Risk - RR 0.39, 95% CI 0.23–0.66, and RR 0.68, 95% CI 0.46–0.99, respectively), but no apparent effect on major CV events [ 49 ]. A larger meta-analysis including 30 trials (N = 18,585) concluded that xanthine oxidase inhibitors produced a 6.0% reduction in relative risk for major adverse cardiovascular events, mainly because of the benefit attributed to allopurinol (RR: 0.61, 95% CI 0.46–0.80, I 2 = 21.0%), while febuxostat would have a more neutral effect (RR: 1.09, 95% CI 0.998–1.19, I 2 = 0.0%) [ 50 ].…”