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

[摘要] 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 mug/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 mug/kg/min, respectively. Dobutamine, for 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 equal to 15% increase in stroke volume (SV) at 23 h to 24 h; 2) a greater than or equal to 25% decrease in pulmonary capillary wedge pressure (PCWP) land greater than or equal to4 mm Hg) at 23 h to 24 h; 3) a greater than or equal to 40% increase in cardiac output (CO) (with change in heart rate [HR] <20%); 4) a 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 less than or equal to 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 mug/kg followed 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 College of Cardiology.

[发布日期] 2000-11-15