Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy

Eur Heart J. 2019 Jun 7;40(22):1778-1786. doi: 10.1093/eurheartj/ehz119.

Abstract

Aims: To compare the occurrence of cerebral, cardiovascular, and renal events in patients with hyperuricaemia treated with febuxostat and those treated with conventional therapy with lifestyle modification.

Methods and results: This multicentre, prospective, randomized open-label, blinded endpoint study was done in 141 hospitals in Japan. A total of 1070 patients were included in the intention-to-treat population. Elderly patients with hyperuricaemia (serum uric acid >7.0 to ≤9.0 mg/dL) at risk for cerebral, cardiovascular, or renal disease, defined by the presence of hypertension, Type 2 diabetes, renal disease, or history of cerebral or cardiovascular disease, were randomized to febuxostat and non-febuxostat groups and were observed for 36 months. Cerebral, cardiovascular, and renal events and all deaths were defined as the primary composite event. The serum uric acid level at endpoint (withdrawal or completion of the study) in the febuxostat (n = 537) and non-febuxostat groups (n = 533) was 4.50 ± 1.52 and 6.76 ± 1.45 mg/dL, respectively (P < 0.001). The primary composite event rate was significantly lower in the febuxostat group than in non-febuxostat treatment [hazard ratio (HR) 0.750, 95% confidence interval (CI) 0.592-0.950; P = 0.017] and the most frequent event was renal impairment (febuxostat group: 16.2%, non-febuxostat group: 20.5%; HR 0.745, 95% CI 0.562-0.987; P = 0.041).

Conclusion: Febuxostat lowers uric acid and delays the progression of renal dysfunction.

Registration: ClinicalTrials.gov (NCT01984749).

Keywords: Cardiovascular disease; Cerebral disease; Elderly patient; Febuxostat; Hyperuricaemia; Renal disease.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases* / complications
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2
  • Febuxostat / therapeutic use*
  • Female
  • Gout Suppressants / therapeutic use*
  • Humans
  • Hyperuricemia* / complications
  • Hyperuricemia* / drug therapy
  • Hyperuricemia* / epidemiology
  • Kidney Diseases* / complications
  • Kidney Diseases* / epidemiology
  • Kidney Diseases* / prevention & control
  • Male
  • Prospective Studies
  • Uric Acid / blood

Substances

  • Gout Suppressants
  • Febuxostat
  • Uric Acid

Associated data

  • ClinicalTrials.gov/NCT01984749