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Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION‐HEART multicentre randomised trial
Author(s) -
ComínColet Josep,
Manito Nicolás,
SegoviaCubero Javier,
Delgado Juan,
García Pinilla José Manuel,
Almenar Luis,
CrespoLeiro María G.,
Sionis Alessandro,
Blasco Teresa,
PascualFigal Domingo,
GonzalezVilchez Francisco,
LambertRodríguez José Luis,
Grau María,
Bruguera Jordi
Publication year - 2018
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.1145
Subject(s) - medicine , levosimendan , heart failure , placebo , clinical endpoint , ambulatory , adverse effect , hazard ratio , confidence interval , natriuretic peptide , cardiology , randomized controlled trial , anesthesia , alternative medicine , pathology
Aims The LION‐HEART study was a multicentre, double‐blind, randomised, parallel‐group, placebo‐controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure. Methods and results Sixty‐nine patients from 12 centres were randomly assigned at a 2:1 ratio to levosimendan or placebo groups, receiving treatment by a 6‐hour intravenous infusion (0.2 μg/kg/min without bolus) every 2 weeks for 12 weeks. The primary endpoint was the effect on serum concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health‐related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT‐proBNP over time for patients who received levosimendan was significantly lower than for the placebo group (344 × 10 3 [95% Confidence Interval (CI) 283 × 10 3 −404 × 10 3 ] vs. 535 × 10 3 [443 × 10 3 −626 × 10 3 ], p = 0.003). In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11–0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time ( P = 0.022). Adverse event rates were similar in the two treatment groups. Conclusions In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT‐proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials.