Levosimendan for Hemodynamic Support after Cardiac Surgery

CHEETAH Study Group

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%] , respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P = 0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P = 0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P = 0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P = 0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.). © Copyright 2017 Massachusetts Medical Society. All rights reserved.
Original languageEnglish
Pages (from-to)2021-2031
Number of pages11
JournalNew England Journal of Medicine
Volume376
Issue number21
DOIs
Publication statusPublished - 2017

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Thoracic Surgery
Hemodynamics
Placebos
Confidence Intervals
Mortality
Intensive Care Units
Medical Futility
simendan
Medical Societies
Left Ventricular Dysfunction
Artificial Respiration
Hypotension
Meta-Analysis
Cardiac Arrhythmias
Length of Stay
Survival Rate
Body Weight
Health

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Levosimendan for Hemodynamic Support after Cardiac Surgery. / CHEETAH Study Group.

In: New England Journal of Medicine, Vol. 376, No. 21, 2017, p. 2021-2031.

Research output: Contribution to journalArticle

CHEETAH Study Group. / Levosimendan for Hemodynamic Support after Cardiac Surgery. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 21. pp. 2021-2031.
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title = "Levosimendan for Hemodynamic Support after Cardiac Surgery",
abstract = "BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9{\%}] and 33 patients [12.8{\%}] , respectively; absolute risk difference, 0.1 percentage points; 95{\%} confidence interval [CI], -5.7 to 5.9; P = 0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95{\%} CI, -5 to 1; P = 0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95{\%} CI, -21 to 2; P = 0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95{\%} CI, -1 to 2; P = 0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.). {\circledC} Copyright 2017 Massachusetts Medical Society. All rights reserved.",
author = "G Landoni and VV Lomivorotov and G Alvaro and R Lobreglio and A Pisano and F Guarracino and MG Calabr{\`o} and EV Grigoryev and VV Likhvantsev and MF Salgado-Filho and A Bianchi and VV Pasyuga and Massimo Baiocchi and F Pappalardo and F Monaco and VA Boboshko and MN Abubakirov and B Amantea and R Lembo and L Brazzi and L Verniero and P Bertini and AM Scandroglio and T Bove and Alessandro Belletti and MG Michienzi and DL Shukevich and TS Zabelina and Rinaldo Bellomo and A Zangrillo and {CHEETAH Study Group}",
year = "2017",
doi = "10.1056/NEJMoa1616325",
language = "English",
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pages = "2021--2031",
journal = "New England Journal of Medicine",
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TY - JOUR

T1 - Levosimendan for Hemodynamic Support after Cardiac Surgery

AU - Landoni, G

AU - Lomivorotov, VV

AU - Alvaro, G

AU - Lobreglio, R

AU - Pisano, A

AU - Guarracino, F

AU - Calabrò, MG

AU - Grigoryev, EV

AU - Likhvantsev, VV

AU - Salgado-Filho, MF

AU - Bianchi, A

AU - Pasyuga, VV

AU - Baiocchi, Massimo

AU - Pappalardo, F

AU - Monaco, F

AU - Boboshko, VA

AU - Abubakirov, MN

AU - Amantea, B

AU - Lembo, R

AU - Brazzi, L

AU - Verniero, L

AU - Bertini, P

AU - Scandroglio, AM

AU - Bove, T

AU - Belletti, Alessandro

AU - Michienzi, MG

AU - Shukevich, DL

AU - Zabelina, TS

AU - Bellomo, Rinaldo

AU - Zangrillo, A

AU - CHEETAH Study Group

PY - 2017

Y1 - 2017

N2 - BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%] , respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P = 0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P = 0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P = 0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P = 0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.). © Copyright 2017 Massachusetts Medical Society. All rights reserved.

AB - BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%] , respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P = 0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P = 0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P = 0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P = 0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.). © Copyright 2017 Massachusetts Medical Society. All rights reserved.

U2 - 10.1056/NEJMoa1616325

DO - 10.1056/NEJMoa1616325

M3 - Article

VL - 376

SP - 2021

EP - 2031

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 21

ER -