Author + information
- Received October 8, 1999
- Revision received June 14, 2000
- Accepted July 25, 2000
- Published online November 15, 2000.
- Markku S. Nieminen, MD, FACC, FESC∗,* (, )
- Juha Akkila, MSc†,
- Gerd Hasenfuss, MD, FACC‡,
- Franz X. Kleber, MD, PhD§,
- Lasse A. Lehtonen, MD, PhD†,
- Veselin Mitrovic, MD∥,
- Olof Nyquist, MD, PhD¶,
- Willem J. Remme, MD, PhD, FACC#,
- on behalf of the Study Group∗∗
- ↵*Reprint requests and correspondence:
Professor Markku S. Nieminen, Chief, Division of Cardiology, Helsinki University Central Hospital, Haartmaninkatu 4, SF-00290 Helsinki, Finland.
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.
Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure.
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 μg/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 μg/kg/min, respectively. Dobutamine, for comparative purposes, was given as an open-label infusion (6 μg/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a ≥15% increase in stroke volume (SV) at 23 h to 24 h; 2) a ≥25% decrease in pulmonary capillary wedge pressure (PCWP) (and ≥4 mm Hg) at 23 h to 24 h; 3) a ≥40% increase in cardiac output (CO) (with change in heart rate [HR] <20%); 4) a ≥50% decrease in PCWP during two consecutive measurements.
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 ≤ 0.001). Headache (9%), nausea (5%) and hypotension (5%) were the most frequently reported adverse events at higher dosages.
Dosing of levosimendan with a 10-min bolus of 6 to 24 μg/kg followed by an infusion of 0.05 to 0.2 μg/kg/min is well tolerated and leads to favorable hemodynamic effects.
↵∗∗ Investigators and centers are listed in the acknowledgments.
☆ This study was supported by Orion Pharma, Espoo, Finland.
- Received October 8, 1999.
- Revision received June 14, 2000.
- Accepted July 25, 2000.
- American College of Cardiology