Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period : The multinational randomized LeoDOR trial

• 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 12weeks. 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 mu g/kg/min every 2weeks, or as 24 h infusion at a rate of 0.1 mu g/kg/min every 3weeks. The primary efficacy assessment after 14weeks 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 26weeks, 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 14weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12- 7.68; p= 0.021) and 26weeks (HR 1.64, 95% CI 0.87- 3.11; p= 0.122). Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability. [GRAPHICS.]

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

Levosimendan

Acute heart failure

Randomised controlled trial

Hospitalization

N-terminal pro-B-type natriuretic peptide

Global rank endpoint

Publication and Content Type

ref (subject category)

art (subject category)