Levosimendan in patients with left ventricular dysfunction undergoing cardiac surgery: a meta-analysis and trial sequential analysis of randomized trials

Patients with left ventricular dysfunction (LVD) undergoing cardiac surgery have a high mortality rate. Levosimendan, a calcium sensitizer, improves myocardial contractility without increasing myocardial oxygen demand. It is not clear whether levosimendan can reduce mortality in cardiac surgery patients with LVD. The PubMed, Embase, and Cochrane Central databases were searched to identify randomized trials comparing levosimendan with conventional treatment in cardiac surgery patients with LVD. We derived pooled risk ratios (RRs) with random effects models. The primary endpoint was perioperative mortality. Secondary endpoints were renal replacement treatment, atrial fibrillation, myocardial infarction, ventricular arrhythmia, and hypotension. Fifteen studies enrolling 2606 patients were included. Levosimendan reduced the incidence of perioperative mortality (RR: 0.64, 95%CI: 0.45-0.91) and renal replacement treatment (RR:0.71, 95%CI:0.52-0.95). However, sensitivity analysis, subgroup analysis and Trial Sequential Analysis (TSA) indicated that more evidence was needed. Furthermore, levosimendan did not reduce the incidence of atrial fibrillation (RR:0.82, 95%CI:0.64-1.07), myocardial infarction (RR:0.56, 95%CI:0.26-1.23), or ventricular arrhythmia (RR:0.74, 95%CI:0.49-1.11), but it increased the incidence of hypotension (RR:1.11,95%CI:1.00-1.23). There was not enough high-quality evidence to either support or contraindicate the use of levosimendan in cardiac surgery patients with LVD.