Levosimendan in patients with reduced left ventricular function undergoing isolated coronary or valve surgery.

Abstract

OBJECTIVE:

In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures.

METHODS:

Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs.

RESULTS:

The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165).

CONCLUSIONS:

Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.

• Authors: Sean van Diepen, Rajendra H Mehta, Jeffrey D Leimberger, Shaun G Goodman, Stephen Fremes, Rachael Jankowich, Matthias Heringlake, Kevin J Anstrom, Jerrold H Levy, John Luber, A Dave Nagpal, Andra E Duncan, Michael Argenziano, Wolfgang Toller, Kevin Teoh, J David Knight, Renato D Lopes, Patricia A Cowper, Daniel B Mark, John H Alexander
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 159 Issue 6 Pg. 2302-2309.e6 (06 2020) ISSN: 1097-685X [Electronic] United States
• PMID: 31358329 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Video-Audio Media)
• Copyright: Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cardiotonic Agents
• Simendan

Topics

• Aged
• Cardiotonic Agents (adverse effects, economics, therapeutic use)
• Coronary Artery Bypass (adverse effects, economics, mortality)
• Coronary Artery Disease (economics, mortality, physiopathology, surgery)
• Cost-Benefit Analysis
• Double-Blind Method
• Drug Costs
• Female
• Heart Valve Diseases (economics, mortality, physiopathology, surgery)
• Heart Valve Prosthesis Implantation (adverse effects, economics, mortality)
• Hospital Costs
• Humans
• Male
• Middle Aged
• Postoperative Complications (economics, mortality, therapy)
• Risk Assessment
• Risk Factors
• Simendan (adverse effects, economics, therapeutic use)
• Time Factors
• Treatment Outcome
• Ventricular Dysfunction, Left (drug therapy, economics, mortality, physiopathology)
• Ventricular Function, Left (drug effects)