Effect of Urate-Lowering Therapy on Cardiovascular and Renal Outcomes: A Systematic Review and Meta-Analysis

Background: Several clinical practice guidelines noted the potential benefits of urate-lowering therapy (ULT) on cardiovascular disease (CVD) and chronic kidney disease (CKD) progression, however effect of this regimen remains much uncertainty. In this systematic review, we aimed to evaluate the efficacy of ULT on major adverse cardiovascular events(MACEs), all-cause mortality and kidney failure events. Methods: We systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through April 2019. We included prospective, randomized, controlled trials assessing the effects of ULT on cardiovascular or renal outcomes. We extracted published data and did a meta-analysis of urate-lowering therapy on relative risks (RRs) of major adverse cardiovascular events, all-cause mortality, kidney failure events, and adverse events. Summary estimates of RR reductions were calculated with a random effects model. Findings: We identified 28 trials including a total of 9194 participants, of which 5070 participants received ULT, 4104 participants received placebo, usual-care or no treatment. Finally, 1279 MACEs, 377 deaths and 87 kidney failure events were recorded. Among all the population with 3103 (34·18%) participants having chronic kidney disease and 5718 (61·14%) having cardiovascular disease or stroke, ULT reduced the risk of MACEs [risk ratio (RR) 0·80, 95% confidence interval (CI) 0·67-0·95; I2 = 42·7%] and all-cause mortality (RR 0·80, 95% CI 0·66-0·97; I2 =0·0%), but had no effect on kidney failure (RR 1·04, 95%CI 0·43-2·42; I2 =64·4%). There was no significant difference (RR=0·99, 95% CI 0·95 to 1·03; I2 =55·7%) in the risk of adverse events between the participants receiving ULT and the control group. Interpretation: ULT has a beneficial effect on reducing the risk of MACEs and all-cause mortality. However, there is insufficient evidence to support an effect of ULT in reducing risk of kidney failure events. Funding Statement: This work was funded by National Key Research and Development Program of China (2018YFC1314004). JL was supported by the grant from the National Natural Science Foundation of China (no. 81270795), JZ was supported by the National Natural Science Foundation of China (81874401). Dr Badve is supported by a John Chalmers Clinical Research Fellowship with the support of Servier from The George Institute for Global Health. Declaration of Interests: Dr Badve reports grants from the National Health and Medical Research Council of Australia, personal fees from Bayer AG and Amgen Australia, and nonfinancial support from Bayer AG. Other authors listed in this paper declare no competing interests. Ethics Approval Statement: This study is registered with PROSPERO, number CRD42018104227.