Superiority of long-acting to short-acting loop diuretics in the treatment of congestive heart failure

Circ J. 2012;76(4):833-42. doi: 10.1253/circj.cj-11-1500.


Background: Diuretics are the most prescribed drug in heart failure (HF) patients. However, clinical evidence about their long-term effects is lacking. The purpose of this study was to compare the therapeutic effects of furosemide and azosemide, a short- and long-acting loop diuretic, respectively, in patients with chronic heart failure (CHF).

Methods and results: In this multicenter, prospective, randomized, open, blinded endpoint trial, we compared the effects of azosemide and furosemide in patients with CHF and New York Heart Association class II or III symptoms. 320 patients (160 patients in each group, mean age 71 years) were followed up for a minimum of 2 years. The primary endpoint was a composite of cardiovascular death or unplanned admission to hospital for congestive HF. During a median follow-up of 35.2 months, the primary endpoint occurred in 23 patients in the azosemide group and in 34 patients in the furosemide group (hazard ratio [HR], 0.55, 95% confidence interval [CI] 0.32-0.95: P=0.03). Among the secondary endpoints, unplanned admission to hospital for congestive HF or a need for modification of the treatment for HF were also reduced in the azosemide group compared with the furosemide group (HR, 0.60, 95%CI 0.36-0.99: P=0.048).

Conclusions: Azosemide, compared with furosemide, reduced the risk of cardiovascular death or unplanned admission to hospital for congestive HF.

Trial registration: NCT00355667.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Chi-Square Distribution
  • Chronic Disease
  • Disease-Free Survival
  • Female
  • Furosemide / adverse effects
  • Furosemide / therapeutic use*
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Hospitalization
  • Humans
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use*
  • Sulfanilamides / adverse effects
  • Sulfanilamides / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Sodium Potassium Chloride Symporter Inhibitors
  • Sulfanilamides
  • Furosemide
  • azosemide

Associated data