Open AccessEfficacy and safety of intermittent repeated levosimendan infusions in advanced heart failure patients: the LAICA study
Author(s) -
GarcíaGonzález Martín J.,
Aldea Perona Ana,
Lara Padron Antonio,
Morales Rull José Luis,
MartínezSellés Manuel,
Mora Martin Manuel,
López Díaz Javier,
López Fernandez Silvia,
Ortiz Oficialdegui Pilar,
Jiménez Sosa Alejandro
Publication year - 2021
Publication title -
esc heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.787
H-Index - 25
ISSN - 2055-5822
DOI - 10.1002/ehf2.13670
Subject(s) - levosimendan , medicine , acute decompensated heart failure , clinical endpoint , decompensation , heart failure , placebo , incidence (geometry) , hazard ratio , adverse effect , randomized controlled trial , cardiology , anesthesia , confidence interval , physics , alternative medicine , pathology , optics
Aims The aim of the LAICA study was to evaluate the long‐term effectiveness and safety of intermittent levosimendan infusion in patients with advanced heart failure (AdHF). Methods and results This was a multicentre, randomized, double‐blind, placebo‐controlled clinical trial of intermittent levosimendan 0.1 μg/kg/min as a continuous 24‐h intravenous infusion administered once monthly for 1 year in patients with AdHF. The primary endpoint [incidence of rehospitalization (admission to the emergency department or hospital ward for >12 h) for acute decompensated HF or clinical deterioration of the underlying HF] occurred in 23/70 (33%) of the levosimendan group (Group I) and 12/27 (44%) of the placebo group (Group II) ( P = 0.286). The incidence of hospital readmissions for acute decompensated HF (Group I vs. Group II) at 1, 3, 6, and 12 months was 4.2% vs. 18.2% ( P = 0.036); 12.8% vs. 33.3% ( P = 0.02); 25.7% vs. 40.7% ( P = 0.147); 32.8% vs. 44.4% ( P = 0.28), respectively. In a secondary pre‐specified time‐to‐event analysis no differences were observed in admission for acute decompensated HF between patients treated with levosimendan compared with placebo (hazard ratio 0.66; 95% CI, 0.32–1.32; P = 0.24). Cumulative incidence for the aggregated endpoint of acute decompensation of HF and/or death at 1 and 3 months were significatively lower in the levosimendan group than in placebo group [5.7% vs. 25.9% ( P = 0.004) and 17.1% vs. 48.1% ( P = 0.001), respectively], but not at 6 and 12 months [34.2% vs. 59.2% ( P = 0.025); 41.4% vs. 66.6% ( P = 0.022), respectively]. Survival probability was significantly higher in patients who received levosimendan compared with those who received placebo (log rank: 4.06; P = 0.044). There were no clinically relevant differences in tolerability between levosimendan and placebo and no new safety signals were observed. Conclusions In our study, intermittent levosimendan in patients with AdHF produced a statistically non‐significant reduction in the incidence of hospital readmissions for acute decompensated HF, a significantly lower cumulative incidence of acute decompensation of HF and/or death at 1 and 3 month of treatment and a significant improvement in survival during 12 months of treatment.