The Possible Impact of Levosimendan Infusions on Clinical Course of Heart Failure. The results of the LEIA-HF Study

Aims Intermittent administration of levosimendan has recently been introduced for long-term use in patients with advanced heart failure (HF). However, the impact of this therapy on survival remains inconclusive. Methods LEIA-HF (Levosimendan in Ambulatory Heart Failure Patients) was a multicenter, randomized, double-blind, placebo-controlled, phase IV clinical trial of intermittent levosimendan administration in patients with ambulatory stable advanced heart failure (left ventricular ejection fraction ≤35%, NYHA class III-IV). The primary composite endpoint (CEP) of the study was composed of death from any cause or unplanned hospitalization for heart failure, whichever occurred first in a 12-month follow-up period. Infusion started at a dose of 0.05 μg/kg/min and lasted approximately 24 hours (up to a maximum dose of 12.5mg) every 4 weeks. The study was conducted in 9 centers around Poland. The study was prematurely terminated due to excess of deaths in the active treatment group. Finally, 64 (out of 350 planned) patients were recruited to the study. Results Sixty-four patients with advanced HF (age - 64.2±13.1 years, 57 (89%) men) were enrolled into the study. At baseline visit 34 (53%) patients were randomly assigned to the levosimendan group (study group), and 30 (47%) to the placebo group. Study drug administration resulted in a significant decrease of NT-proBNP concentrations (5084 pg/mL [306–23.203] vs. 2027 pg/mL [872-2174], p=0.02) and LVEF improvement (20.9±5.9% vs. 29.27±5.23%, p=0.015) in the study group. These patients also had CEP numerically more often than patients in the placebo group [22 (64.71%) vs. 14 (46.67%); p = 0.14]; including significantly higher deaths [7 (100%) vs 0, p=0.02]. Conclusions In a selected group of stable ambulatory advanced heart failure (left ventricular ejection fraction ≤35%, NYHA class III-IV) patients, repetitive levosimendan 24-hour infusion might be an additional therapeutic option but observed deaths may raise its safety issue.