Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomised controlled trials

Introduction: Patients undergoing coronary revascularization often require inotropic support that has been associated with an increased risk for death and morbidity. The purpose of this study was to evaluate the effect of levosimendan versus control on survival after coronary revascularization. Methods: A systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of levosimendan compared to other therapy in patients having coronary revascularisaion. The databases searched were Pubmed, EMBASE, the Cochrane Registry of Clinical Trials and the metaRegister of Controlled Trials. Studies that compared levosimendan to any other therapy for coronary revascularisation in adult humans and reported at least one outcome of interest were considered for inclusion. Both percutaneous coronary intervention and cardiac surgery were included. Data extraction was performed independently by two reviewers using predefined criteria. Relevant outcomes included mortality, cardiac index, cardiac enzymes, length of stay and post-procedural atrial fibrillation. Results: The meta-analysis included 729 patients from 17 studies. Levosimendan was associated with a mortality reduction after coronary revascularization, (19/386 in the levosimendan group vs 39/343 in the control arm) odds ratio (OR) 0.40 (95% confidence interval (CI) 0.21 to 0.76, P for overall effect 0.005, P for heterogeneity = 0.33, I-2 = 12% with a total of 729 patients. Levosimendan also had a favourable effect on cardiac index (standardised mean difference 1.63, 95% CI 1.43 to 1.83, P for overall effect < 0.00001), length of intensive care stay (random effects model, mean difference -26.18 hours 95% CI 46.20 to 6.16, P for heterogeneity < 0.00001, I-2 = 95%, P for overall effect P = 0.01), reductions in the rate of atrial fibrillation (OR 0.54, 95% CI 0.36 to 0.82, P for effect = 0.004, P for heterogeneity 0.84, I-2 = 0% for 465 patients) and troponin I levels group (mean difference -1.59, 95% CI 1.78 to 1.40, P for overall effect < 0.00001, P for heterogeneity < 0.00001, I-2 = 95%). Limitations of this analysis are discussed. Conclusions: Levosimendan is associated with a significant improvement in mortality after coronary revascularization. There are also improvements in several secondary endpoints. A suitably powered randomised controlled trial is required to confirm these findings and to address the unresolved questions about the timing and dosing of levosimendan.