Levosimendan Infusion versus Dobutamine - LIDO


The goal of the Levosimendan Infusion versus Dobutamine (LIDO) study was to assess the safety and efficacy of levosimendan as compared to dobutamine among patients with severe low-output heart failure.


Levosimendan infusion in patients with severe low-output heart failure would be associated with an improved hemodynamic response when compared to dobutamine infusion.

Study Design

Study Design:

Patients Screened: 476
Patients Enrolled: 203
NYHA Class: IV
Mean Follow Up: 180 days
Mean Patient Age: >21 years
Female: 8
Mean Ejection Fraction: <35%

Patient Populations:

Patients admitted to the hospital with low-output heart failure who were judged to require hemodynamic monitoring and treatment with intravenous inotropic agents


Age younger than 21 years, childbearing potential, heart failure due to restrictive or hypertrophic cardiomyopathy or to uncorrected stenotic valvular disease, chest pain at the time of randomization, sustained ventricular tachycardia or ventricular fibrillation within the previous two weeks, atrioventricular block of second or third degree, heart rate more than 120 beats/minute at rest, systolic blood pressure below 85 mm Hg, severe renal failure, hepatic failure, cardiac tamponade, adult respiratory distress syndrome, and septic shock

Primary Endpoints:

The proportion of patients who achieved hemodynamic improvement (i.e., an increase in cardiac output by 30% or a decrease in the mean pulmonary capillary wedge pressure of 25%) at 24 hours

Secondary Endpoints:

Changes from baseline in hemodynamic variables other than cardiac output and pulmonary-capillary wedge pressure at 24 hours; changes from baseline to 24 hours in symptoms of heart failure; proportion of patients needing intravenous rescue therapy with positive inotropic drugs, vasodilators, or diuretics during the infusion of the study drug; number of days alive and out of the hospital and not receiving intravenous drugs during the first month; time to development of worsening heart failure or death; and mortality at six months

Drug/Procedures Used:

Eligible patients were randomized to receive either a levosimendan infusion or a dobutamine infusion. Levosimendan was initiated with an infusion of 24 mcg/kg over 10 minutes followed by a 0.1 mcg/kg/min infusion. Dobutamine was started with an infusion of 5 mcg/kg/min with no loading dose.

To maintain blinding, patients were given two simultaneous infusions: one active drug and one placebo. The infusions were administered for 24 hours and titrated every two hours until an increase in cardiac index of 30% was achieved.

Principal Findings:

Twenty-eight percent of the levosimendan group and 15% of the dobutamine group achieved significant hemodynamic improvement (i.e., an increase in cardiac output by 30% or a decrease in the mean pulmonary capillary wedge pressure of 25%) (hazard ratio 1.9, p=0.022). At 180 days, there was significantly lower mortality in the levosimendan group (26% vs. 38%, p=0.029).


Among patients with severe low-output heart failure, levosimendan was associated with an improvement in hemodynamic response at 24 hours and a decrease in mortality at 180 days when compared to dobutamine. In an era with increasing use of beta-blockers in patients with heart failure, it is important to note that the effects of levosimendan were not attenuated by beta-blockers as they were with dobutamine.


Follath F, Cleland JG, Just H, et al., on behalf of the Steering Committee and Investigators of the Levosimendan Infusion versus Dobutamine (LIDO) Study. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002;360:196-202.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Phosphodiesterase Inhibitors, Dobutamine, Pulmonary Wedge Pressure, Heart Failure, Cardiac Output, Hydrazones, Vasodilator Agents, Cardiotonic Agents, Pyridazines

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