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May 11, 2021Frontiers in Cardiovascular MedicineOpen Access

Effect of Uric Acid-Lowering Agents on Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

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Key result

Uric acid-lowering therapies did not significantly improve left ventricular ejection fraction (MD 1.63%), 6-minute walk test, BNP levels, or mortality compared to placebo in heart failure patients.

Why the study?

Elevated serum uric acid is an independent predictor of adverse outcomes in cardiovascular disease, but the causal relationship between uric acid-lowering therapies and heart failure remains controversial.

Do uric acid-lowering therapies improve clinical and surrogate outcomes in patients with heart failure?

Population

Patients with heart failure across randomised controlled trials

Comparison

Uric acid-lowering therapies vs control

Design

Systematic review and meta-analysis of randomised controlled trials

Authors

HXHongxuan XuYLYunqing LiuLMLing‐bing Meng

Discussion

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Overview

May reduce HF hospitalizations in HFpEF without mortality benefit; leaves open need for confirmatory RCTs.

Study Design

Type

Meta-Analysis (n=864)

Structured PICO

Do uric acid-lowering therapies improve clinical and surrogate outcomes in patients with heart failure?

P
Population
864 adult patients with heart failure from 6 randomized controlled trials, followed for a median of 10 weeks.
I
Intervention
Uric acid-lowering therapies (xanthine oxidase inhibitors [allopurinol, oxypurinol] and uricosuric drugs [benzbromarone, probenecid])
C
Comparator
Placebo or control
O
Outcome
Left ventricular ejection fraction (LVEF), 6-Minute Walk Test (6MWT), BNP/NT-pro-BNP, all-cause mortality, and cardiovascular death

Main Result

Mean Difference: 1.63 (95% CI -1.61–4.88)

p-value: p=0.32

Uric acid-lowering therapies do not improve cardiac function, exercise capacity, or mortality in patients with heart failure, suggesting uric acid may be a risk marker rather than a causal factor.

Limitations

  • Small overall sample size
  • Potential heterogeneity due to different patient inclusion/exclusion criteria and dosing protocols
  • Various durations of included studies
  • Potential publication bias
  • Did not include the XO selective drug febuxostat
  • Different patient inclusion and exclusion criteria
  • Different dosing protocols
  • Various study durations

Cite This Study

Xu et al. (2021) conducted a meta-analysis in Heart failure (n=864). Uric acid-lowering therapies vs. Placebo was evaluated on Left ventricular ejection fraction (LVEF) (MD 1.63%, 95% CI -1.61 to 4.88, p=0.32). Uric acid-lowering therapies did not significantly improve left ventricular ejection fraction (MD 1.63%), 6-minute walk test, BNP levels, or mortality compared to placebo in heart failure patients.

synapsesocial.com/papers/6a903f356bfd95d7bd4dd404https://doi.org/10.3389/fcvm.2021.639392
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients2015 · 297 citations
  2. 2Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure2005 · 105 citations
  3. 3Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy2001 · 437 citations
  4. 4Heart Disease and Stroke Statistics—2013 Update2012 · 5,193 citations
  5. 5Changes in the vasoactive effects of nitric oxide, hydrogen sulfide and the structure of the rat thoracic aorta: the role of age and essential hypertension.2018 · 35 citations