Repetitive use of levosimendan for treatment of chronic advanced heart failure: Clinical evidence, practical considerations, and perspectives: An expert panel consensus

Abstract

The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure

“…Several small observational and randomized studies were reviewed19 and summarized30 and recently updated22 in meta‐analysis and suggested that in selected patients, repetitive or intermittent levosimendan appears promising and may improve outcomes including mortality but selection criteria may need improvement. However, in SURVIVE, levosimendan was associated with borderline better 31 day survival compared with dobutamine in the majority of patients with a history of HF prior to the relevant ADHF episode (hazard ratio 0.52–1.03, P for interaction = 0.05), consistent with a potential benefit in stable patients with chronic HF.…”

“…Continuous outpatient conventional inotrope infusions may be required to keep patients out of hospital and to preserve perfusion and end organ function, for example, in patients awaiting heart transplantation, especially those who may not be suitable for bridging with left ventricular assist device (LVAD). However, this practice is still controversial and may be associated with increased mortality 17, 18, 19…”

“…This has led to a growing but highly variable practice of intermittent (as needed) or repetitive (planned) treatment in advanced but stable HF 21. This may be beneficial in select patients 19, 22. The LevoRep trial did show improved 6 min walking capacity and improved Kansas City Cardiomyopathy Questionnaire but did not meet the high primary endpoint criteria; however, effects on secondary endpoints were promising 23.…”

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

“…A panel of international experts recently proposed criteria for the identification of the patients most likely to benefit from repetitive use of levosimendan in chronic AdHF [36]. Among those were patients listed for heart transplantation or LVAD implantation, as well as patients with similar clinical profiles but not eligible to LVAD or transplantation due to other causes (i.e.…”

“…Evidence of clinical benefit was brought forward [36,37] although data on the subject are heterogeneous both in terms of methodology and of results: the comparator of levosimendan varied from placebo to diuretics, or dobutamine; the dosages and interval of levosimendan administration differed among centers; there was marked variation in these study design, as the primary and secondary outcomes.…”