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Network Meta-Analysis of Drug Therapies for Lowering Uric Acid and Mortality Risk in Patients with Heart Failure

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Abstract

Purpose

This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF).

Methods

Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%).

Results

Nine studies, which included seven different types of groups, were eligible for analysis. The “untreated uricemia” group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the “no uricemia” group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08–1.89)). The “start-allo” group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the “untreated uricemia” group (RR (95% CI), 0.68 (0.45–1.01)). However, in the “start-allo” group the SUCRA value was comparable to that in the “no uricemia” group (SUCRA: 65.4% for “start-allo”; 64.1% for “no uricemia”).

Conclusions

Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.

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Acknowledgments

All authors thank Ms. Haga and Ms. Chino in the Niigata University for their excellent secretarial work.

Funding

The study was funded by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (ID:19K12840). The sponsor had no influence over the design and conduct of the study; collection, management, analysis, and interpretation of the data or preparation, review; or approval of the manuscript.

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Contributions

All authors conceived and designed the research; SK, KF, CH, MY, MK, and YY acquired the data; SK, KF, and HS analyzed the data; SK drafted the manuscript; and SK, TY, TM, YM, KW, and HS interpreted the results and made critical revision of the manuscript for important intellectual content. All authors approved the submission of the final manuscript.

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Correspondence to Satoru Kodama.

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Kodama, S., Fujihara, K., Horikawa, C. et al. Network Meta-Analysis of Drug Therapies for Lowering Uric Acid and Mortality Risk in Patients with Heart Failure. Cardiovasc Drugs Ther 35, 1217–1225 (2021). https://doi.org/10.1007/s10557-020-07097-4

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