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Effect of Urate-Lowering Therapy on Cardiovascular and Kidney Outcomes: A Systematic Review and Meta-Analysis
Qi Chen1, Zi Wang2, Jingwei Zhou1
1Department of Nephrology, Dongzhimen Hospital, The First Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China.
Insights
Urate-lowering therapy did not improve major adverse cardiovascular events, all-cause mortality, or kidney failure in patients. While it slowed GFR decline and lowered BP, evidence does not support its use for kidney and cardiovascular outcomes.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Clinical practice guidelines suggest urate-lowering therapy may benefit cardiovascular disease and chronic kidney disease (CKD).
- However, the efficacy of urate-lowering therapy for major adverse cardiovascular events (MACE), kidney failure, and mortality remains uncertain.
- This systematic review evaluates the impact of urate-lowering therapy on key clinical outcomes.
Purpose of the Study:
- To systematically evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events (MACE).
- To assess the effect of urate-lowering therapy on all-cause mortality, kidney failure events, blood pressure (BP), and glomerular filtration rate (GFR).
Main Methods:
- A systematic literature search was conducted across MEDLINE, Embase, and Cochrane databases for trials published up to July 2020.
- Prospective, randomized, controlled trials of at least 6 months duration assessing urate-lowering therapy effects on cardiovascular or kidney outcomes were included.
- Random effects meta-analysis was used to summarize treatment effects from 28 trials involving 6458 participants.
Main Results:
- Urate-lowering therapy did not significantly reduce MACE (RR, 0.93; 95% CI, 0.74-1.18), all-cause mortality (RR, 1.04; 95% CI, 0.78-1.39), or kidney failure (RR, 0.97; 95% CI, 0.61-1.54).
- However, it attenuated GFR decline (WMD, 1.18 ml/min/1.73 m²/year; 95% CI, 0.44-1.91) and lowered systolic BP (WMD, -3.45 mm Hg; 95% CI, -6.10 to -0.80) and diastolic BP (WMD, -2.02 mm Hg; 95% CI, -3.25 to -0.78).
- No significant difference in adverse events was observed between the treatment and control groups (RR, 1.01; 95% CI, 0.94-1.08).
Conclusions:
- Urate-lowering therapy demonstrated no significant benefits for major adverse cardiovascular events, all-cause mortality, or kidney failure.
- The therapy did show a positive effect on slowing GFR decline and reducing blood pressure.
- Currently, there is insufficient evidence to support the use of urate-lowering therapy specifically for improving kidney and cardiovascular outcomes.
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.
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