Effect of levosimendan on survival and adverse events after cardiac surgery: a meta-analysis.

OBJECTIVE Left ventricular systolic dysfunction is associated with increased morbidity and mortality in patients undergoing cardiac surgery. The authors performed a meta-analysis investigating the effects of levosimendan in cardiac surgery patients with and without preoperative systolic dysfunction. DESIGN Meta-analysis of randomized controlled trials. SETTING Hospital. PARTICIPANTS The 1,155 patients who participated in 14 randomized controlled trials of perioperative levosimendan were included. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS PubMed, EMBASE, the Cochrane database of clinical trials, and conference proceedings were searched for clinical trials of perioperative levosimendan in patients undergoing cardiac surgery through May 1, 2012. Studies were grouped by mean ejection fraction (EF). Those with a mean EF <40% were designated as low-EF. Pooled results demonstrated a reduction in mortality with levosimendan (risk difference [RD]-4.2%; 95% CI -7.2%, -1.1%; p = 0.008). Subgroup analysis showed that this benefit was confined to the low-EF studies (RD -7.0%; 95% CI -11.0%, -3.1%; p < 0.001). No benefit was observed in the preserved-EF subgroup (RD +1.1%; 95% CI -3.8%, +5.9%; p = 0.66). Significant reductions also were seen in the need for dialysis (RD -4.9%; 95% CI -8.2%, -1.6%; p = 0.003), myocardial injury (RD -5.0%; 95% CI -8.3%, -1.7%; p = 0.003), and postoperative atrial fibrillation (RD -8.1%; 95% CI -13.3%, -3.0%; p = 0.002). CONCLUSIONS Levosimendan was associated with reduced mortality and other adverse outcomes in patients undergoing cardiac surgery, and these benefits were greatest in patients with reduced EF. These data support the need for adequately powered randomized clinical trials to confirm the benefits of levosimendan in patients with reduced EF undergoing cardiac surgery.