Effect of Uric Acid-Lowering Agents on Cardiovascular Outcome in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Clinical Studies

Angiology. 2020 Apr;71(4):315-323. doi: 10.1177/0003319719897509. Epub 2020 Jan 31.

Abstract

Several trials have been completed in patients with heart failure (HF) treated with uric acid (UA)-lowering agents with inconsistent results. We aimed to investigate whether lowering UA would have an effect on mortality and cardiovascular (CV) events in patients with HF in a systematic review and meta-analysis. The primary outcome measures were all-cause mortality, CV mortality, CV events, and CV hospitalization in patients with HF. We included 11 studies in our final analysis. Overall, allopurinol treatment was associated with a significant increase in the risk for all-cause mortality (hazard ratio [HR]: 1.24, 95% confidence interval [CI]: 1.04-1.49, P = .02). The trial heterogeneity is high (heterogeneity χ2 = 37.3, I2 = 73%, P < .001). With regard to CV mortality, allopurinol treatment was associated with a 42% increased risk of CV mortality (HR: 1.42, 95% CI: 1.11-1.81, P = .005). There was a trend toward increased CV hospitalization in the same group (HR: 1.21, 95% CI: 0.95-1.53, P = .12). Uric acid-lowering treatments increase all-cause and CV mortality but did not increase CV hospitalization significantly in this study.

Keywords: allopurinol; cardiovascular mortality; febuxostat; heart failure; uric acid.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Allopurinol / therapeutic use
  • Enzyme Inhibitors / therapeutic use*
  • Febuxostat / therapeutic use
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Oxypurinol / therapeutic use
  • Uric Acid
  • Xanthine Oxidase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Febuxostat
  • Uric Acid
  • Allopurinol
  • Xanthine Oxidase
  • Oxypurinol