Prophylactic levosimendan in patients with low ejection fraction undergoing coronary artery bypass grafting: A pooled analysis of two multicentre randomised controlled trials

Thibaut Caruba, Anaïs Charles-Nelson, John H. Alexander, Rajendra H. Mehta, Matthias Heringlake, Wolfgang Toller, Amelie Yavchitz, Brigitte Sabatier, Gilles Chatellier, Bernard Cholley

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Objectives: To assess the effect of preoperative levosimendan on mortality at day 90 in patients with left ventricular ejection fraction (LVEF) ≤ 40%, and to investigate a possible differential effect between patients undergoing isolated coronary artery bypass grafting (CABG) versus CABG combined with valve replacement surgery. Design: Pooled analysis of two multicentre randomised controlled trials (RCT) investigating prophylactic levosimendan versus placebo prior to CABG surgery on mortality at day 90 in patients with LVEF ≤ 40%. A meta-analysis of all RCT investigating the same issue was also conducted. Results: A cohort of 1084 patients (809 isolated CABG, and 275 combined surgery) resulted from the merging of LEVO-CTS and LICORN databases. Seventy-two patients were dead at day 90. The mortality at day 90 was not different between levosimendan and placebo (Hazard Ratio (HR): 0.73, 95% CI: 0.41–1.28, p = 0.27). However, there was a significant interaction between the type of surgery and the study drug (p = 0.004). We observed a decrease in mortality at day 90 in the isolated CABG subgroup (HR: 0.39, 95% CI: 0.19–0.82, p = 0.013), but not in the combined surgery subgroup (HR: 1.73, 95% CI: 0.77–3.92, p = 0.19). The meta-analysis of 6 RCT involving 1441 patients confirmed the differential effect on mortality at day 30 between the 2 subgroups. Conclusions: Preoperative levosimendan did not reduce mortality in a mixed surgical population with LV dysfunction. However, the subgroup of patients undergoing isolated CABG had a reduction in mortality at day 90, whereas there was no significant effect in combined surgery patients. This finding requires confirmation with a specific prospective trial.

Original languageEnglish
Article number101107
Number of pages7
JournalAnaesthesia Critical Care and Pain Medicine
Issue number4
Publication statusPublished - Aug 2022
Externally publishedYes


  • Coronary artery bypass surgery (CABG)
  • Levosimendan
  • Mortality
  • Valve replacement surgery

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