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November 29, 2019Critical Care61 citationsOpen Access

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

BCBernard CholleyBLBruno LévyJFJean-Luc Fellahi

Key Result

Levosimendan did not show clear superiority to placebo in recent large trials, but remains a potentially useful inodilator for specific situations like decompensated heart failure on beta-blockers.

Structured PICO

I
Intervention
Levosimendan

While levosimendan lacks proven superiority in broad RCTs, expert consensus suggests it remains a useful inodilator for niche indications such as heart failure patients on beta-blockers, Takotsubo syndrome, and facilitating weaning from mechanical support.

Limitations

  • Current evidence for many niche indications is mostly retrospective or relies on expert opinion.
  • Lack of high-quality randomized studies for indications like cardiogenic shock and Takotsubo syndrome.

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.

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Cite This Study

Cholley et al. (2019) conducted a review in Heart failure, cardiogenic shock, and cardiac surgery. Levosimendan vs. Placebo or classical inotropes was evaluated. Levosimendan did not show clear superiority to placebo in recent large trials, but remains a potentially useful inodilator for specific situations like decompensated heart failure on beta-blockers.

synapsesocial.com/papers/6a1890dca61bfdbaa2c9c8b8https://doi.org/10.1186/s13054-019-2674-4
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Binding of a new Ca2+ sensitizer, levosimendan, to recombinant human cardiac troponin C. A molecular modelling, fluorescence probe, and proton nuclear magnetic resonance study.1994 · 234 citations
  2. 2The inodilator levosimendan as a treatment for acute heart failure in various settings2017 · 24 citations
  3. 3Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies*2011 · 232 citations
  4. 4Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis2016 · 372 citations
  5. 5Effects of Levosimendan and Milrinone on Oxygen Consumption in Isolated Guinea-Pig Heart2004 · 82 citations