Oral levosimendan in patients with severe chronic heart failure --the PERSIST study

Eur J Heart Fail. 2008 Dec;10(12):1246-54. doi: 10.1016/j.ejheart.2008.09.006. Epub 2008 Oct 21.

Abstract

Background: Intravenous levosimendan improves symptoms in acutely decompensated heart failure.

Aims: To evaluate the effects of oral levosimendan in severe chronic heart failure (CHF).

Methods: 307 patients with NYHA IIIB-IV CHF were randomly assigned, double-blind, to levosimendan 1 mg once or twice daily or placebo for at least 180 days. An exploratory primary end-point, the Patient Journey, a composite consisting of repeated symptom assessments, worsening heart failure and mortality during 60 days was used. Minnesota Living with Heart Failure quality of life score (MLHFQoL) and NT-proBNP were assessed repeatedly.

Results: Patients assigned to a lower dose of levosimendan had more severe CHF at baseline. No differences in symptoms emerged and worsening heart failure events and death were similar resulting in a similar Patient Journey score with levosimendan and placebo (p=0.567). Compared to placebo, a net improvement of 3-4 points in MLHFQoL at several time-points in favour of the combined levosimendan groups was observed (p<0.001) which was accompanied by a substantial and persistent reduction in NT-proBNP (-30-40%) (p<0.001).

Conclusion: Levosimendan improved QoL and decreased NT-proBNP but did not improve the Patient Journey composite in patients with severe CHF. Further research with this compound is warranted to clarify safety and efficacy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / therapeutic use*
  • Chronic Disease
  • Disease Progression
  • Double-Blind Method
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Hydrazones / administration & dosage
  • Hydrazones / adverse effects
  • Hydrazones / therapeutic use*
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Natriuretic Peptide, Brain / drug effects
  • Peptide Fragments / blood
  • Peptide Fragments / drug effects
  • Psychometrics
  • Pyridazines / administration & dosage
  • Pyridazines / adverse effects
  • Pyridazines / therapeutic use*
  • Quality of Life
  • Severity of Illness Index
  • Simendan
  • Surveys and Questionnaires

Substances

  • Biomarkers
  • Cardiotonic Agents
  • Hydrazones
  • Peptide Fragments
  • Pyridazines
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Simendan