Levosimendan in Cardiac Surgery: The Evidence Adds Up

If we had a way to reduce the risk of life-threatening complications after cardiac surgery would we use it?  Of course we would. It is for reason that this blog post highlights the recent work of Dr. Qiang and colleagues [1]. In the most up-to-date and comprehensive research of its kind these researchers identified and analysed data from 25 randomised controlled trials (RCTs) that compared perioperative use of levosimendan with control (placebo, conventional inotropes or intra-aortic balloon pump) in 3247 adult cardiac surgery patients and reported an impressive array of benefits. The main results are that:

  1. Levosimendan reduced mortality after cardiac surgery (OR 0.63; P=0.001). This survival benefit was not confined to patients with markedly reduced left ventricular ejection fraction (LVRF), it extended to patients with LVEF up to 50%. So even patients with only moderate depression of LVEF gained from levosimendan treatment.
  2. Levosimendan use also significantly reduced: the incidence of postoperative acute kidney injury (OR 0.55; P<0.0001), the use of renal replacement therapy (OR 0.56; P=0.002), the duration of ICU stay (weighted mean difference [WMD] -0.49 day; P=0.0002), and the duration of mechanical ventilation (WMD -2.30 h; P=0.002).

Data of this sort make a strong case for the peri-operative use of levosimendan in adult cardiac surgery but they can’t answer every question. In particular, the outcomes of some recent randomised trials [2,3,4] points to the need for further work to define the optimal dose-range: Qiang and colleagues [1] suggest that adult cardiac surgery may be a situation where initial bolus dosing and a relatively high infusion rate may be needed to secure the full clinical benefit of levosimendan unique inodilator actions. If that proves indeed to be the case then the well-documented safety profile of levosimendan will be another feature favouring its use.

References

1. Qiang H et al. J Cardiovasc Pharmacol 2018 Publish Ahead of Print Apr 3. PMID: 29672418, DOI: 10.1097/FJC.0000000000000584.

2. Landoni G et al. N Engl J Med. 2017;376(21):2021–2031.

3. Mahta RH et al. N Engl J Med. 2017;376(21):2032–2042.

4. Cholley B et al. JAMA. 2017;318(6):548–556.

 

Publications (13)
  • FIGHT, PERSIST and LEVOREP

    Professor Gerhard Pölzl highlights the significance of the FIGHT, PERSIST and LEVOREP trials which investigate levosimendan as a treatment for heart failure.

  • ESC 2017 in Barcelona

    Professor Gerhard Pölzl discusses the European Society of Cardiology annual meeting 2017, where several sessions were held on the use of levosimendan in heart failure.

  • LEODOR trial - recent advances

    There have been some recent achievements in the LEODOR trial including a new website to facilitate administration and communication and submission of a formal study protocol synopsis to the European Journal of Heart Failure.

  • Levosimendan roars ahead as LION-HEART results published

    Professor Gerhard Pölzl reports primary results from the LION-HEART study in the management of advanced heart failure where among secondary endpoints, patients treated with levosimendan experienced a reduction in the rate of HF-related hospitalisation compared with placebo.

  • What does the Advanced Heart Failure patient want?

    Professor Cynthia M Dougherty and colleagues outline an array of options for the treatment of advanced heart failure (HF) that create – quite reasonably – the impression that we are in a golden age of therapeutic possibilities for this difficult condition.

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