Repetitive Infusion of Levosimendan in Patients with Chronic Heart Failure: A Meta-Analysis

BACKGROUND: Repetitive or intermittent levosimendan infusion is gradually becoming more commonly considered for patients with advanced chronic heart failure. However, previous randomized controlled studies (RCTs) reported conflicting results on the effects of levosimendan when administered repetitively. The aim of this meta-analysis was to generate up-to-date evidence to assess the effect of levosimendan in this group of patients.
MATERIAL AND METHODS: A literature review identified 8 qualified studies. A meta-analysis was performed to assess mortality and left ventricular ejection fraction (LVEF).
RESULTS: Use of levosimendan contributed to significantly reduced mortality at the end of mid-term follow-up. The mortality rates in levosimendan and control group were 23 of 226 (10.2%) and 53 of 198 (26.8%), respectively (RR: 0.40, 95%CI: 0.26–0.63, P<0.0001). The trend of significantly decreased mortality was observed in levosimendan vs. placebo subgroup (RR: 0.28, 95%CI: 0.15–0.54, P=0.0001, I2=0%) but not in levosimendan vs. dobutamine, PGE1, or furosemide subgroup (p=0.19, p=0.64 and p=0.25, respectively). Levosimendan also contributed to significantly improved LVEF improvement at the end of follow-up (mean difference: 3.69%, 95CI: 0.92–6.45%, p=0.009).
CONCLUSIONS: Intermittent or repetitive levosimendan infusion might be a promising strategy to reduce mortality and improve LVEF in patients with advanced chronic, but not necessarily acutely decompensated, heart failure to maintain disease stability.

Keywords: Clinical Trials as Topic, Chronic Disease, Follow-Up Studies, Heart Failure - physiopathology, Hydrazones - therapeutic use, Pyridazines - therapeutic use, Stroke Volume