Levosimendan: a novel inotropic agent for treatment of acute, decompensated heart failure.
OBJECTIVE
To review the literature on a novel calcium sensitizer, levosimendan.


METHODS
Articles were identified through searches of MEDLINE (1966-June 2005), International Pharmaceutical Abstracts (1970-June 2005), and EMBASE (1992-June 2005) using the key words levosimendan, simendan, calcium sensitizer, calcium sensitiser, and congestive heart failure.


METHODS
Clinical trials and pharmacokinetic studies evaluating the safety and efficacy of levosimendan were selected.


RESULTS
Levosimendan 6-24 mug/kg intravenous bolus followed by a 24-hour continuous infusion of 0.05-0.2 microg/kg/min improved cardiac output and reduced pulmonary capillary wedge pressure in a dose-dependent manner. Dose-ranging and randomized clinical trials have demonstrated improvement in symptoms and hemodynamics and short-term survival outcomes in the treatment of acute, decompensated heart failure. Clinical trials evaluating retrospective mortality data and combined endpoints (mortality, rehospitalization) have demonstrated better outcomes with levosimendan compared with dobutamine. The incidence of hypotension with levosimendan is not significantly different than with dobutamine, but there is a dose-related increase in heart rate.


CONCLUSIONS
Levosimendan is useful in moderate to severe low-output heart failure in patients who have failed to respond to diuretics and vasodilators. Based on current studies, levosimendan appears to be a safe alternative to dobutamine for treatment of acute, decompensated heart failure. Prospective clinical trials are needed to confirm the effect of levosimendan on long-term survival and its role in heart failure in the setting of myocardial infarction.
Earl
Grace L
GL
Department of Pharmacy Practice and Administration, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA. g.earl@usip.edu
Fitzpatrick
James T
JT
D000208:Acute Disease; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011724:Pyridazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077464:Simendan; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan