Levosimendan: a calcium-sensitizing agent for the treatment of patients with decompensated heart failure.
Levosimendan is a new inodilator. Its mechanism of action includes calcium sensitization of contractile proteins and the opening of adenosine triphosphate-dependent K channels. The combination of positive inotropy with anti-ischemic effects of K-channel opening offers potential benefits in comparison with currently available intravenous inotropes, which are contraindicated in patients with ongoing myocardial ischemia. Levosimendan has been extensively studied in various animal models of heart failure, in which the drug has increased contractility without adverse effects on diastolic function. These results have been repeated in patients with heart failure, in whom levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. The active metabolite of levosimendan (OR-1896) significantly prolongs the duration of the hemodynamic effects of the therapeutic 24-hour levosimendan infusion. Levosimendan has been studied in two major trials with decompensated patients (LIDO and RUSSLAN), in which it showed outcome benefits in comparison with dobutamine and placebo, respectively. A third comparative study (CASINO) recently suggested mortality benefits with levosimendan over placebo and dobutamine. Currently, two large prospective trials (SURVIVE and REVIVE) in patients who are hospitalized because of worsening heart failure are underway. These trials will conclusively prove whether levosimendan should be added to the standard treatment in patients who are hospitalized because of cardiac decompensation.
Lehtonen
Lasse
L
Department of Clinical Pharmacology, University of Helsinki, Helsinki University Central Hospital, Haartmaninkatu 4, PO Box 360, FIN-00290, Helsinki, Finland. lasse.lehtonen@hus.fi
D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D006334:Heart Function Tests; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D011379:Prognosis; D011446:Prospective Studies; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012720:Severity of Illness Index; D000077464:Simendan; D016019:Survival Analysis; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan