Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper

Abstract

Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.

Can levosimendan reduce ECMO weaning failure in cardiogenic shock?: a cohort study with propensity score analysis

“…Levosimendan is a calcium-sensitizing inotropic agent with systemic, coronary, and pulmonary vasodilatory properties and also specific cardioprotective effects with respect to myocardial oxygen balance [ 8 – 10 ]. It has been approved for the treatment of acute decompensated heart failure, but its efficacy in cardiogenic shock remains questionable [ 11 ]. The use of levosimendan in patients undergoing VA-ECMO might be of interest both to reduce the duration of mechanical support and to minimize severe complications.…”

Effects of levosimendan on weaning and survival in adult cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation: systematic review and meta-analysis

“…Primary outcome: successful VA ECMO weaning. Among the five studies that reported the VA ECMO successful weaning, [20][21][22][23][24] a total of 557 patients was assessed. The pooled VA ECMO weaning was 61.4% (95% CI 39.8-82.9%).…”

“…21 To avoid this complication, low doses of positive inotropic drugs may be needed to maintain the left ventricular ejection and avoid upstream congestion. The specific features of levosimendan may be of interest in this situation: no increase in myocardial oxygen consumption, a prolonged cardiovascular effect, less direct pro-arrhythmic effects, 21 improvement in cardiac function and endothelial function, 33 and without increasing norepinephrine requirements and with similar rates of arrhythmia. 30 Of note, levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties, like acute decompensated heart failure or in advanced chronic heart failure.…”

“…30 Of note, levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties, like acute decompensated heart failure or in advanced chronic heart failure. 21 Regarding cardiac surgery setting, the data were either neutral or inconclusive. 36 However a recent meta-analysis, including also the latest trials, confirms that levosimendan had a significant effect on mortality only when used in case of severe perioperative cardiovascular dysfunction (LVEF ⩽ 30%) in patients receiving cardiac surgery.…”

“…To date, there are limited studies investigating the effects of levosimendan on VA ECMO weaning and its impact on the survival. 21 Therefore, we aimed to conduct a systematic review and meta-analysis to assess the effects of levosimendan on weaning and survival in CS adult patients with VA ECMO.…”