Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap

Drug Des Devel Ther. 2021 Aug 4:15:3391-3409. doi: 10.2147/DDDT.S295214. eCollection 2021.

Abstract

Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. It was first approved in Sweden in 2000 for the short-term treatment of acutely decompensated severe chronic heart failure when conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate. After more than 20 years, clinical applications have considerably expanded across critical care and emergency medicine, and levosimendan is now under investigation in different cardiac settings (eg, septic shock, pulmonary hypertension) and for non-cardiac applications (eg, amyotrophic lateral sclerosis). This narrative review outlines key milestones in levosimendan history, by addressing regulatory issues, pharmacological peculiarities and clinical aspects (efficacy and safety) of a drug that did not receive great attention in the heart failure guidelines. A brief outlook to the ongoing clinical trials is also offered.

Keywords: amyotrophic lateral sclerosis; cardiac surgery; cardiogenic shock; heart failure; levosimendan.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / pharmacology*
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Phosphodiesterase 3 Inhibitors / adverse effects
  • Phosphodiesterase 3 Inhibitors / pharmacology
  • Simendan / pharmacology*
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / pharmacology

Substances

  • Cardiotonic Agents
  • Phosphodiesterase 3 Inhibitors
  • Vasodilator Agents
  • Simendan
  • Adenosine Triphosphate