Continuous infusion of levosimendan yielded a dose-dependent hemodynamic response rate ranging from 50% to 88%, compared with 14% for placebo and 70% for dobutamine (p<=0.001 for dose-response).
RCT (n=151)
Double-blind
Randomized
Yes
Does levosimendan improve hemodynamic parameters in adult patients with NYHA class II-IV heart failure of ischemic origin?
Levosimendan administered as a bolus followed by a 24-hour infusion produces favorable, dose-dependent hemodynamic improvements in patients with ischemic heart failure.
p-value: p=<=0.001
OBJECTIVES: We sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin. BACKGROUND: Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure. METHODS: A double-blind, placebo-controlled, randomized, multicenter, parallel-group study included 151 adult patients. Levosimendan was given as a 10-min intravenous bolus of 3, 6, 12, 24 or 36 microg/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 microg/kg/min, respectively. Dobutamine, for comparative purposes, was given as an open-label infusion (6 microg/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a > or =15% increase in stroke volume (SV) at 23 h to 24 h; 2) a > or =25% decrease in pulmonary capillary wedge pressure (PCWP) (and > or =4 mm Hg) at 23 h to 24 h; 3) a > or =40% increase in cardiac output (CO) (with change in heart rate HR or =50% decrease in PCWP during two consecutive measurements. RESULTS: The response rate to levosimendan ranged from 50% at the lowest dose to 88% at the highest dose (compared with placebo 14%, dobutamine 70%). A dose-response relationship was demonstrated for levosimendan on increases in CO and SV, and reductions in PCWP during the infusion (for all, p< or =0.001). Headache (9%), nausea (5%) and hypotension (5%) were the most frequently reported adverse events at higher dosages. CONCLUSIONS: Dosing of levosimendan with a 10-min bolus of 6 to 24 microg/kg followed by an infusion of 0.05 to 0.2 microg/kg/min is well tolerated and leads to favorable hemodynamic effects.
Nieminen et al. (2000) conducted an RCT in New York Heart Association class II-IV heart failure of ischemic origin (n=151). Levosimendan vs. Placebo and open-label dobutamine (6 microg/kg/min) was evaluated on Proportion of patients achieving >=15% increase in SV, >=25% decrease in PCWP, >=40% increase in CO, or >=50% decrease in PCWP (p=<=0.001). Continuous infusion of levosimendan yielded a dose-dependent hemodynamic response rate ranging from 50% to 88%, compared with 14% for placebo and 70% for dobutamine (p<=0.001 for dose-response).