Key Points
- To evaluate the effect of short-term intravenous infusion of levosimendan compared with dobutamine on long-term survival in patients hospitalized with acute decompensated heart failure requiring inotropic support.
- Randomized, double-blind trial conducted across 75 centers in 9 countries between March 2003 and December 2004, enrolling 1,327 hospitalized patients with acute decompensated heart failure and left ventricular ejection fraction ≤30%.
- Patients were randomized to receive either intravenous levosimendan (n=664; 12-µg/kg loading dose followed by 0.1–0.2 µg/kg/min for 24 hours) or intravenous dobutamine (n=663; starting at ≥5 µg/kg/min up to 40 µg/kg/min for at least 24 hours).
- All-cause mortality at 180 days occurred in 26% (173/664) of patients in the levosimendan group and 28% (185/663) in the dobutamine group (hazard ratio, 0.91; 95% confidence interval, 0.74–1.13; P=.40).
- Levosimendan produced significantly greater decreases in plasma B-type natriuretic peptide levels at 24 hours through day 5 compared with dobutamine (P<.001 for all time points), but yielded no significant differences in 31-day mortality, dyspnea relief, or days alive out of the hospital.
- The levosimendan group experienced higher incidences of atrial fibrillation, hypokalemia, and headache, whereas the dobutamine group experienced a higher incidence of worsening cardiac failure.
Structured PICO
Does intravenous levosimendan reduce all-cause mortality at 180 days compared to dobutamine in patients with acute decompensated heart failure requiring inotropic support?
PPopulation1327 patients hospitalized with acute decompensated heart failure (HF) who required inotropic support after not responding to vasodilators or diuretics, with left ventricular ejection fraction ≤30%.
IInterventionIntravenous levosimendan (12-µg/kg loading dose followed by a 24-hour infusion of 0.1- to 0.2-µg/kg/min) (n=664).
CComparatorIntravenous dobutamine (initiated at ≥5 µg/kg/min and increased incrementally to a maximum of 40 µg/kg/min at the physicians' discretion, given for at least 24 hours) with double placebos (n=663).
OOutcomeAll-cause mortality at 180 dayshard clinical
In patients with acute decompensated heart failure, levosimendan did not improve 180-day survival compared to dobutamine and was associated with a higher incidence of adverse events such as headache and arrhythmias.