Introduction: The LIDO and RUSSLAN trials showed that levosimendan was well tolerated and had a stronger hemodynamic effect than dobutamine and a positive impact on prognosis. There are, however, few data regarding its effectiveness and safety when used in an everyday clinical setting.
Objective: To test the hypothesis that in day-to-day practice conditions levosimendan is both effective and safe for the treatment of decompensated heart failure (HF). This primary combined endpoint of effectiveness and safety was evaluated at 24 hours and 5 days after the beginning of the treatment.
Design: Prospective, multicenter, nonrandomized clinical trial with evaluations at baseline, 24 hours, 5 days, and 3 and 6 months. Follow-up for 6 months.
Setting: The intensive care units of 15 cardiology or internal medicine departments.
Patients: 129 consecutive patients requiring inotropes due to decompensated systolic HF despite maximally tolerated oral therapy.
Intervention: 24-hour infusion of levosimendan via a central or peripheral vein. MEASUREMENTS AND EVALUATION OF RESULTS: 1. Monitoring: Continuous ECG monitoring, non-invasive blood pressure, urinary output, oximetry. Invasive monitoring was not required. 2. Follow-up. Baseline evaluation: history, physical examination, ECG, 2D echocardiogram, hemogram, ionogram, liver and kidney function. 24-hour and 5-day evaluations: symptoms, physical examination, recording of medical therapy and previous 24-hour urinary output, ECG, hemogram, ionogram, liver and kidney function, and evaluation of arrhythmic episodes and heart rate and blood pressure trends in previous 24 hours. 3- and 6-month evaluations: number of hospital admissions and length of hospital stay due to HF, and mortality. 3. Evaluation of primary endpoint.
Effectiveness: assessed by a clinical score including 2 subjective parameters (1. NYHA functional class, 2. patient self-evaluation symptom class) and 6 objective parameters (3. body weight, 4. pulmonary congestion, 5. previous 24-hour diuresis, 6. serum creatinine, 7. oral HF medication, 8. intravenous HF medication). Definition of clinical effectiveness: improvement in > or = 1 subjective parameters plus improvement in > or = 1 objective parameters, with all other parameters unchanged.
Safety: The therapy was judged safe in the absence of any serious adverse event with a probable or undetermined causal relationship with levosimendan. Primary endpoint evaluation: Patients reached the primary endpoint when levosimendan was both effective and safe according to the above definitions.