Efficacy and safety of intermittent repeated levosimendan infusions in advanced heart failure patients: the LAICA study

Abstract

AimsThe 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 resultsThis 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.

Advanced heart failure: guideline‐directed medical therapy, diuretics, inotropes, and palliative care

“…More recently, in the small, multicentre, randomized, placebo‐controlled LION‐HEART trial (Intermittent Intravenous Levosimendan in Ambulatory Advanced Chronic Heart Failure Patients), intermittent levosimendan decreased NT‐proBNP levels and reduced HF rehospitalizations (HR, 0.25; 95% CI, 0.11–0.56; P = 0.001) 88 . Similar results were reported in other small studies 89–92 . The ongoing LeoDOR study (NCT03437226) will assess the efficacy and safety of repetitive levosimendan given for 12 weeks in advanced HF patients 93 …”

“…88 Similar results were reported in other small studies. [89][90][91][92] The ongoing LeoDOR study (NCT03437226) will assess the efficacy and safety of repetitive levosimendan given for 12 weeks in advanced HF patients. 93 Randomized controlled trials with drugs acting through an increase in intracellular calcium failed to prove benefits in terms of outcome, with an increase in mortality in some cases.…”

Intermittent Inotrope Infusion Associated with Peritoneal Dialysis for Management of Advanced Heart Failure Secondary to Cardiac Amyloidosis

“…Otaviano et al Inotrope for Advanced HF Due to Amyloidosis these studies, intermittent infusion of levosimendan showed a significant reduction in acute decompensation and death in the first and third month in the intervention group. 5 In another study, the use of the drug as a 6-hour infusion (0.2 mcg/kg/min), without bolus, every 2 weeks for 12 weeks, was associated with a lower hospitalization risk with similar adverse events when compared to placebo and, importantly, with savings for the health system. 6,7 Furthermore, repeated or intermittent infusion for patients with advanced HF was associated with a reduction in 3-month rehospitalizations; this strategy was considered safe and well tolerated in patients with HF who required inotropes, with remarkable improvements in quality of life and functional capacity.…”

Use of Levosimendan in Patients with Advanced Heart Failure: An Update

“…In the LAICA (efficacy and safety of intermittent repeated levosimendan infusions in advanced heart failure patients) study, 97 patients were randomized to levosimendan (0.1 μg/kg/min as a continuous 24-h intravenous infusion administered once monthly for 1 year) vs. placebo [ 42 ]. In this trial, levosimendan did not reduce the rate of readmissions for acute decompensated HF (HR 0.66; 95% CI, 0.32–1.32; p = 0.24).…”