Changeover Trial of Febuxostat and Topiroxostat for Hyperuricemia with Cardiovascular Disease: Sub-Analysis for Chronic Kidney Disease (TROFEO CKD Trial)

Ann Thorac Cardiovasc Surg. 2020 Aug 20;26(4):202-208. doi: 10.5761/atcs.oa.19-00162. Epub 2019 Nov 21.

Abstract

Background: The TROFEO trial demonstrated that febuxostat causes greater and more rapid reduction of serum uric acid (s-UA) than topiroxostat. We compared these drugs in patients with chronic kidney disease (CKD) by sub-analysis of the TROFEO trial.

Methods: This sub-analysis targeted patients with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2. The primary endpoint was the s-UA level. Secondary endpoints included creatinine, eGFR, urinary albumin, cystatin-C, oxidized low-density lipoprotein (Ox-LDL), eicosapentaenoic acid/arachidonic acid ratio, lipid biomarkers, high-sensitivity C-reactive protein, and B-type natriuretic peptide (BNP).

Results: There was no significant difference of s-UA between the two groups either before or after treatment. However, s-UA did not exceed 6.0 mg/dL in febuxostat group during the study period, but it exceeded this level in seven patients from topiroxostat group, with the number being significantly higher in topiroxostat group. Serum creatinine (s-Cr) and eGFR were significantly better after 6 months of febuxostat treatment compared with topiroxostat Cystatin-C was significantly lower after 6 months of febuxostat treatment compared with topiroxostat. The Ox-LDL was significantly lower after 3 and 6 months of febuxostat treatment compared with topiroxostat.

Conclusion: Febuxostat had stronger renoprotective and antioxidant effects than topiroxostat in patients with hyperuricemia and CKD.

Keywords: febuxostat; gout; hyperuricemia; topiroxostat; xanthine oxidase.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antioxidants / adverse effects
  • Antioxidants / therapeutic use*
  • Biomarkers / blood
  • Cross-Over Studies
  • Down-Regulation
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Febuxostat / adverse effects
  • Febuxostat / therapeutic use*
  • Female
  • Glomerular Filtration Rate
  • Gout Suppressants / adverse effects
  • Gout Suppressants / therapeutic use*
  • Humans
  • Hyperuricemia / blood
  • Hyperuricemia / complications
  • Hyperuricemia / diagnosis
  • Hyperuricemia / drug therapy*
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / physiopathology
  • Time Factors
  • Treatment Outcome
  • Uric Acid / blood*
  • Xanthine Oxidase / antagonists & inhibitors

Substances

  • Antioxidants
  • Biomarkers
  • Enzyme Inhibitors
  • Gout Suppressants
  • Nitriles
  • Pyridines
  • FYX-051
  • Febuxostat
  • Uric Acid
  • Xanthine Oxidase