Levosimendan versus placebo in cardiac surgery: a systematic review and meta-analysis

The aim of this meta-analysis was to review all published randomized clinical trials comparing levosimendan versus placebo in patients undergoing cardiac surgery. PubMed, EMBASE and the Cochrane library database of clinical trials were searched for prospective randomized clinical trials investigating the perioperative use of levosimendan versus placebo in patients undergoing adult cardiac surgery from 1 May 2000 to 10 April 2017. Binary outcomes from individual studies were analysed to compute individual and pooled risk ratios (RRs) with pertinent 95% confidence intervals (CIs). Fourteen randomized clinical trials with a total of 2243 patients were included in this review. Overall meta-analysis results demonstrated that levosimendan was associated with a significant reduction in 30-day mortality (RR = 0.71, 95% CI = 0.53-0.95; P = 0.023). Subgroup analysis showed that this benefit was confined to the moderate and low ejection fraction studies (RR = 0.44, 95% CI = 0.27-0.70; P < 0.001), whereas no benefit was observed in the preserved ejection fraction studies (RR = 1.06, 95% CI = 0.72-1.56; P = 0.78). Levosimendan also reduced the risk of renal replacement therapy (RR = 0.66, 95% CI = 0.47-0.92; P = 0.015) and low cardiac output (RR = 0.40, 95% CI = 0.22-0.73; P = 0.003). No significant differences were detected, between the levosimendan group and the placebo group, in terms of risk of myocardial injury (RR = 0.90, 95% CI = 0.69-1.17; P = 0.44), intensive care unit stay (weighted mean differences = -0.57, 95% CI = -1.15 to 0.01; P = 0.055) and the use of ventricular assist device (RR = 0.42, 95% CI = 0.07-2.63; P = 0.35). In conclusion, levosimendan was associated with a reduced risk of mortality, renal replacement therapy and low cardiac output syndrome in patients undergoing cardiac surgery.