Author + information
- Received December 5, 2012
- Revision received December 21, 2012
- Accepted December 28, 2012
- Published online April 1, 2013.
- Milton Packer, MD∗∗ (, )
- Wilson Colucci, MD†,
- Lloyd Fisher, PhD‡,
- Barry M. Massie, MD§,
- John R. Teerlink, MD§,
- James Young, MD‖,
- Robert J. Padley, MD¶,
- Roopal Thakkar, MD¶,
- Leticia Delgado-Herrera, RPh¶,
- Jeffrey Salon, MD¶,
- Chris Garratt, MB, ChB#,
- Bidan Huang, PhD¶,
- Toni Sarapohja, MSc#,
- REVIVE Heart Failure Study Group
- ↵∗Reprint requests and correspondence:
Dr. Milton Packer, Department of Clinical Sciences, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75225.
Background This study evaluated the efficacy and safety of levosimendan, a positive inotropic drug with vasodilator effects, given intravenously to patients with acutely decompensated heart failure (ADHF).
Methods We performed 2 sequential trials, the first to develop a new measure of efficacy in 100 patients, and the second to use this measure to evaluate levosimendan in an additional 600 patients. Patients admitted with ADHF received placebo or intravenous levosimendan for 24 h in addition to standard treatment. The primary endpoint was a composite that evaluated changes in clinical status during the first 5 days after randomization.
Results In the 600-patient trial, more levosimendan than placebo patients (58 vs. 44) were improved at all 3 pre-specified time points (6 h, 24 h, and 5 days), whereas fewer levosimendan patients (58 vs. 82) experienced clinical worsening (p = 0.015 for the difference between the groups). These differences were apparent, despite more frequent intensification of adjunctive therapy in the placebo group (79 vs. 45 patients). Improvements in patient self-assessment and declines in B-type natriuretic peptide levels with levosimendan persisted for 5 days and were associated with reduced length of stay (p = 0.009). Similar findings were present in the 100-patient pilot trial. Levosimendan was associated with more frequent hypotension and cardiac arrhythmias during the infusion period and a numerically higher risk of death across the 2 trials (49 of 350 on a regimen of levosimendan vs. 40 of 350 on a regimen of placebo at 90 days, p = 0.29).
Conclusions In patients with ADHF, intravenous levosimendan provided rapid and durable symptomatic relief. As dosed in this trial, levosimendan was associated with an increased risk of adverse cardiovascular events. (Evaluation of Intravenous Levosimendan Efficacy in the Short Term Treatment of Decompensated Chronic Heart Failure; NCT00048425)
Abbott and Orion Pharma funded the REVIVE program. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 5, 2012.
- Revision received December 21, 2012.
- Accepted December 28, 2012.
- American College of Cardiology Foundation