Rehospitalization after intermittent levosimendan treatment in advanced heart failure patients: a meta-analysis of randomized trials.

AIMS: Intermittent levosimendan administration has been suggested to improve survival in patients with advanced heart failure (AdHF). Quality of life is a key issue for AdHF patients and is negatively affected by frequent hospitalizations.

METHODS AND RESULTS: CENTRAL, Google Scholar, MEDLINE/PubMed, Scopus, and the Cochrane Central Register of clinical trials (updated 15/1/2017) were searched for randomized controlled trials investigating the effect of intermittent levosimendan administration in patients with AdHF. The primary outcome was the number of patients requiring rehospitalization 3 months after the end of treatment. A total of 319 patients from six trials were included. Overall pooled analysis showed that the use of levosimendan was associated with a significant reduction in the number of rehospitalizations at 3 months: 33/207 (16%) vs. 39/113 (35%), risk ratio 0.40, 95% confidence interval 0.27-0.59, P < 0.001, I2  = 0%. This result was confirmed by sensitivity analyses.

CONCLUSIONS: Within the limitations of this meta-analysis including also studies in which endpoints were not independently adjudicated and not clearly specified, repetitive or intermittent administration of levosimendan for patients with AdHF was associated with a reduction in the rehospitalization rate at 3 months. Large, high-quality randomized controlled trials are needed to confirm this finding.