Intermittent levosimendan improves mid-term survival in chronic heart failure patients: Meta-analysis of randomised trials

Aims: Standard inotropic treatment is often necessary in end-stage heart failure but may be harmful. We performed a meta-analysis of randomized controlled trials to investigate the effect of repeated administration of levosimendan on survival in patients with chronic heart failure. Methods and results: Four investigators independently searched in CENTRAL, Google Scholar MEDLINE/PubMed, Scopus and the Cochrane Central Register of clinical trials to identify any randomized study ever performed with intermittent levosimendan intravenous administration in adult patients with chronic heart failure with no restrictions on dose or time of administration. Data from a total of 326 patients from six randomized controlled studies using intermittent levosimendan in a cardiological setting were included in the analysis. Levosimendan was associated with a significant reduction in mortality at the longest follow-up available [32 of 168 (19 %) in the levosimendan group 46 of 133 (35 %) in the control arm, RR = 0.55 (95 % CI 0.37-0.84), p for effect = 0 0.005, p for heterogeneity = 0.3, I ² = 23.4 %, NNT = 6 with 5 studies included]. Brain natriuretic peptide values, ejection fraction and number of patients with New York Heart Association ≥III status were similar in survivors of both groups. Conclusions: A large randomized trial is necessary to confirm the promising beneficial effects of intermittent levosimendan administration on the mid-term survival of patients with chronic heart failure.