Effect of Urate-Lowering Therapy on Cardiovascular and Kidney Outcomes

Abstract

Background and objectives Several clinical practice guidelines noted the potential benefits of urate-lowering therapy on cardiovascular disease and CKD progression; however, the effect of this regimen remains uncertain. In this systematic review, we aimed to evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events, all-cause mortality, kidney failure events, BP, and GFR. Design, setting, participants, & measurements We systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through July 2020. We included prospective, randomized, controlled trials assessing the effects of urate-lowering therapy for at least 6 months on cardiovascular or kidney outcomes. Relevant information was extracted into a spreadsheet by two authors independently. Treatment effects were summarized using random effects meta-analysis. Results We identified 28 trials including a total of 6458 participants with 506 major adverse cardiovascular events and 266 kidney failure events. Overall urate-lowering therapy did not show benefits on major adverse cardiovascular events (risk ratio, 0.93; 95% confidence interval, 0.74 to 1.18) and all-cause mortality (risk ratio, 1.04; 95% confidence interval, 0.78 to 1.39) or kidney failure (risk ratio, 0.97; 95% confidence interval, 0.61 to 1.54). Nevertheless, urate-lowering therapy attenuated the decline in the slope of GFR (weighted mean difference, 1.18 ml/min per 1.73 m2 per year; 95% confidence interval, 0.44 to 1.91) and lowered the mean BP (systolic BP: weighted mean difference,-3.45 mm Hg; 95% confidence interval,-6.10 to-0.80; diastolic BP: weighted mean difference,-2.02 mm Hg; 95% confidence interval,-3.25 to-0.78). There was no significant difference (risk ratio, 1.01; 95% confidence interval, 0.94 to 1.08) in the risk of adverse events between the participants receiving urate-lowering therapy and the control group. Conclusions Urate-lowering therapy did not produce benefits on the clinical outcomes, including major adverse cardiovascular events, all-cause mortality, and kidney failure. Thus, there is insufficient evidence to support urate lowering in patients to improve kidney and cardiovascular outcomes.