Repetitive Levosimendan Infusions for Patients with Advanced Chronic Heart Failure in the Vulnerable Post-Discharge Period: The Multinational Randomized LeoDOR Trial
Gerhard Pölzl, Johann Altenberger, Josep Comín‐Colet, Juan F. Delgado, Francesco Fedele, Martín J. García‐González, Finn Gustafsson, Josep Masip, Zoltán Papp, Stefan Störk, Hanno Ulmer, Sarah Maier, Bojan Vrtovec, Gerhard Wikström, Endre Zima, Axel Bauer, for the LeoDOR Investigators
Abstract
AIM: The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF). METHODS AND RESULTS: In this prospective multicentre, double-blind, two-armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12 weeks. All patients had left ventricular ejection fraction (LVEF) ≤30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 μg/kg/min every 2 weeks, or as 24 h infusion at a rate of 0.1 μg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26 weeks, respectively. Due to the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p = 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14 weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12-7.68; p = 0.021) and 26 weeks (HR 1.64, 95% CI 0.87-3.11; p = 0.122). CONCLUSIONS: Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability.