Levosimendan use in patients with preoperative low ejection fraction undergoing cardiac surgery: A systematic review with meta-analysis and trial sequential analysis.

Objectives: Patients with preoperative low left ventricular ejection fraction (LVEF) are known to be associated with high morbidities and mortality in cardiac surgery. The primary aim of this review was to examine the clinical outcomes of levosimendan versus placebo in patients with preoperative low LVEF ≤ 50% undergoing cardiac surgery.

Data Sources: MEDLINE, EMBASE, PubMed and CENTRAL were searched systematically from their inception until June 2018.

Review Methods: All the randomised clinical trials (RCTs) were included.

Results: Twelve trials were eligible (n = 1867) for inclusion in the data synthesis. In comparison to the placebo cohort, the levosimendan cohort showed a significant reduction in mortality (TSA = inconclusive; ρ = 0.002; I = 0%; FEM: OR 0.56; 95% CI 0.39, 0.80), especially in the subgroups of preoperative severe low LVEF ≤ 30% (ρ = 0.003; OR 0.33; 95% CI 0.16, 0.69), preoperative administering of levosimendan (ρ = 0.001; OR 0.46; 95% CI 0.29, 0.74) and patients who had bolus followed by infusion of levosimendan (ρ = 0.005; OR 0.50; 95% CI 0.30, 0.81). However, the effect on mortality was not significant in the subgroup analysis of high quality trials (ρ = 0.14; OR 0.73; 95% CI 0.47, 1.12). The levosimendan cohort showed a significantly lower incidence of low-cardiac-output-syndrome (ρ < 0.001; OR 0.58; 95% CI 0.46, 0.74) and lesser need for mechanical support of cardiac assist devices (ρ = 0.02; OR 0.39; 95% CI 0.18, 0.86).

Conclusions: Given the low level of evidence and inconclusive TSA, the results of this meta-analysis neither support nor oppose the use of levosimendan in cardiac patients with preoperative low LVEF ≤ 50%. Therefore, multi-centre, adequately powered, randomised controlled trials are warranted.

Prospero Registration: CRD42017067572.