Influence of xanthine oxidase inhibitors on all-cause mortality in adults: a systematic review and meta-analysis

Cardiol J. 2024;31(3):479-487. doi: 10.5603/cj.97807. Epub 2024 May 21.

Abstract

Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between urate-lowering therapy and all-cause mortality in different chronic diseases to match its users and non-users in a real-world setting. Overall, 11 studies were included, which reported adjusted hazard ratios for all-cause mortality over at least 12 months. Meta-analysis of all included studies showed no effect of the therapy on all-cause mortality. However, subgroup analyses showed its beneficial effect in patients with chronic kidney disease (14% risk reduction) and hyperuricemia (14% risk reduction), but not in patients with heart failure (28% risk increase). Urate-lowering therapy reduces all-cause mortality among patients with hyperuricemia and chronic kidney disease, but it seems to increase mortality in patients with heart failure and should be avoided in this subgroup.

Keywords: all-cause mortality; allopurinol; febuxostat; hyperuricemia; xanthine oxidase inhibitors.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Adult
  • Allopurinol / therapeutic use
  • Cause of Death* / trends
  • Enzyme Inhibitors / therapeutic use
  • Febuxostat / therapeutic use
  • Gout Suppressants / therapeutic use
  • Heart Failure / drug therapy
  • Heart Failure / mortality
  • Humans
  • Hyperuricemia* / blood
  • Hyperuricemia* / drug therapy
  • Hyperuricemia* / mortality
  • Renal Insufficiency, Chronic / mortality
  • Risk Factors
  • Uric Acid / blood
  • Xanthine Oxidase* / antagonists & inhibitors

Substances

  • Xanthine Oxidase
  • Enzyme Inhibitors
  • Allopurinol
  • Gout Suppressants
  • Febuxostat
  • Uric Acid