Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study (J-DHF)

Eur J Heart Fail. 2013 Jan;15(1):110-8. doi: 10.1093/eurjhf/hfs141. Epub 2012 Sep 14.


Aims: The therapeutic strategy for heart failure with preserved ejection fraction (HFPEF) has not been established. The Japanese Diastolic Heart Failure Study (J-DHF) is a multicentre, prospective, randomized, open, blinded-endpoint trial, designed to assess the effects of carvedilol in HFPEF patients.

Methods and results: A total of 245 patients with heart failure and ejection fraction >40% were randomly assigned into those treated with (carvedilol group, n = 120) and without carvedilol (control group, n = 125). The primary outcome is a composite of cardiovascular death and unplanned hospitalization for heart failure. During a median follow-up of 3.2 years, the primary endpoint occurred in 29 patients in the carvedilol group and in 34 patients in the control group [adjusted hazard ratio (HR) 0.902, 95% confidence interval (CI) 0.546-1.488, P = 0.6854]. Another major composite endpoint, cardiovascular death and unplanned hospitalization for any cardiovascular causes, occurred in 38 patients of the carvedilol group and 52 patients of the control group (HR 0.768, 95% CI 0.504-1.169; P = 0.2178). The target dose of carvedilol was 20 mg/day, but the median prescribed dose was 7.5 mg/day. In the patients treated with standard doses (carvedilol >7.5 mg/day, n = 58), this composite outcome was significantly less than in the controls (HR 0.539, 95% CI 0.303-0.959; P = 0.0356), whereas it was comparable with the controls in the patients treated with carvedilol ≤7.5 mg/day (n = 62, HR 1.070, 95% CI 0.650-1.763; P = 0.7893).

Conclusions: Carvedilol did not improve prognosis of HFPEF patients overall; however, the standard dose, not the low dose, prescription might be effective. This may facilitate further investigation. UMIN number: C000000318.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use
  • Aged
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Female
  • Follow-Up Studies
  • Heart Failure, Diastolic / drug therapy*
  • Heart Failure, Diastolic / epidemiology
  • Heart Failure, Diastolic / physiopathology
  • Hospitalization / trends*
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Propanolamines / therapeutic use*
  • Prospective Studies
  • Single-Blind Method
  • Stroke Volume / drug effects
  • Stroke Volume / physiology*
  • Treatment Outcome


  • Adrenergic alpha-1 Receptor Antagonists
  • Carbazoles
  • Propanolamines
  • Carvedilol