Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure

OBJECTIVES We sought to define the therapeutic dose range of levosimendan i n patients with New York Heart Association class II-IV heart failure of isc hemic origin. BACKGROUND Levosimendan is a calcium sensitizer for treatment of acute deco mpensated heart failure. METHODS A double-blind, placebo-controlled, randomized, multicenter, parall el-group study included 151 adult patients. Levosimendan was given as a 10- min intravenous bolus of 3, 6, 12, 24 or 36 mug/kg, followed by a 24-h infu sion of 0.05, 0.1, 0.2, 0.4 or 0.6 mug/kg/min, respectively. Dobutamine, fo r comparative purposes, was given as an open-label infusion (6 mug/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a greater than or eq ual to 15% increase in stroke volume (SV) at 23 h to 24 h; 2) a greater tha n or equal to 25% decrease in pulmonary capillary wedge pressure (PCWP) lan d greater than or equal to4 mm Hg) at 23 h to 24 h; 3) a greater than or eq ual to 40% increase in cardiac output (CO) (with change in heart rate [HR] <20%); 4) a <greater than or equal to>50% decrease in PCWP during two conse cutive measurements. RESULTS The response rate to levosimendan ranged from 50% at the lowest dos e 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 less t han or equal to 0.001). Headache (9%), nausea (5%) and hypotension (5%) wer e the most frequently reported adverse events at higher dosages. CONCLUSIONS Dosing of levosimendan with a 10-min bolus of 6 to 24 mug/kg fo llowed by an infusion of 0.05 to 0.2 mug/kg/min is well tolerated and leads to favorable hemodynamic effects, a Am Coil (C) 2000 by the American Colle ge of Cardiology.