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: Pub Med, 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% Cl -7.2%, -1.1%; p = 0.008). Subgroup analysis showed that this benefit was confined to the low-EF studies (RD -7.0%; 95% Cl -11.0%, -3.1%; p < 0.001). No benefit was observed in the preserved-EF subgroup (RD +1.1%; 95% Cl -3.8%, +5.9%; p = 0.66). Significant reductions also were seen in the need for dialysis (RD -4.9%; 95% Cl -8.2%, -1.6%; p = 0.003), myocardial injury (RD -5.0%; 95% Cl -8.3%, -1.7%; p = 0.003), and postoperative atrial fibrillation (RD -8.1%; 95% Cl -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. (C) 2013 Elsevier Inc. All rights reserved.