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N Engl J Med. 2017 May 25;376(21):2032-2042. doi: 10.1056/NEJMoa1616218. Epub 2017 Mar 19.

Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery.

Author information

1
From the Duke Clinical Research Institute, Duke University School of Medicine, Durham (R.H.M., J.D.L., J.M., A.W., R.W.H., J.H.L., K.J.A., J.H.A.), and Tenax Therapeutics, Morrisville (R.J., D.H.) - both in North Carolina; the Canadian VIGOUR (Virtual Coordinating Centre for Global Collaborative Cardiovascular Research) Centre, University of Alberta, Edmonton (S.D., S.G.G.), Sunnybrook Health Sciences Centre, Toronto (S.F.), the Quebec Heart and Lung Institute, Quebec (D.K.), London Health Sciences Centre, London, ON (D.N.), and the Victoria Heart Institute Foundation, Victoria, BC (J.B.) - all in Canada; Cleveland Clinic Foundation (A.D., E.G.S.) and University Hospitals Cleveland Medical Center (S.P.) - both in Cleveland; Franciscan Health System, Tacoma, WA (J.L.); Columbia University Medical Center, New York (M.A.); Spectrum Health, Grand Rapids, MI (E.M.); the Heart Hospital Baylor Plano, Plano, TX (R.M.); the Medical University of Graz, Graz, Austria (W.T.); the University of Luebeck, Luebeck, Germany (M.H.); and the Department of Medicine, Stanford University, Stanford, CA (R.A.H.).

Abstract

BACKGROUND:

Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery.

METHODS:

In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5.

RESULTS:

A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups.

CONCLUSIONS:

Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621 .).

PMID:
28316276
DOI:
10.1056/NEJMoa1616218
[Indexed for MEDLINE]
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