AUTHOR=Ying Hangying , Yuan Hongdi , Tang Xiaomei , Guo Wenpu , Jiang Ruhong , Jiang Chenyang 

TITLE=Impact of Serum Uric Acid Lowering and Contemporary Uric Acid-Lowering Therapies on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.641062

DOI=10.3389/fcvm.2021.641062

ISSN=2297-055X

ABSTRACT=<p><bold>Objective:</bold> This study aimed to evaluate the potential association between uric acid (UA) lowering and cardiovascular risk reduction among UA-lowering therapies in adults.</p><p><bold>Methods:</bold> A systematic search for randomized controlled trials (RCTs) was conducted according to the protocol pre-registered in PROSPERO (No. CRD42020199259). We search for RCTs in PubMed, Embase, Web of Science, the Cochrane Library, and <ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> up to July 1, 2020. A meta-analysis was performed using a fixed- or random-effects model.</p><p><bold>Results:</bold> In total, 30 studies involving 18,585 hyperuricaemic patients were included. Xanthine oxidase inhibitor (XOI) therapy produced a 6.0% reduction in relative risk (RR) for major adverse cardiovascular events (MACEs). The use of febuxostat was associated with a higher risk of cardiovascular events (CVEs) (RR: 1.09, 95% CI 0.998–1.19, <italic>I</italic><sup>2</sup> = 0.0%), but the difference was not statistically significant. Allopurinol treatment was associated with a lower CVE risk (RR: 0.61, 95% CI 0.46–0.80, <italic>I</italic><sup>2</sup> = 21.0%). Among the UA-lowering therapies, the drug treatments were associated with all-cause mortality (RR: 1.20, 95% CI 1.02–1.41, <italic>I</italic><sup>2</sup> = 0.0%). The subgroup with a UA endpoint &lt;7 mg/dl was not associated with a higher CVE risk (RR: 0.57, 95% CI 0.35–0.92, <italic>I</italic><sup>2</sup> = 0.0%), and in the subgroup with a UA endpoint &lt;5 mg/dl group, a lower risk of CVEs was not observed (RR: 0.99, 95% CI 0.69–1.44, <italic>I</italic><sup>2</sup> = 0.0%).</p><p><bold>Conclusions:</bold> UA reduction caused by XOIs reduced the incidence of MACEs. UA-lowering medicines were associated with changes in all-cause mortality but not cardiovascular outcomes. The lower UA endpoint was not associated with reduced cardiovascular risk.</p>