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Crit Care. 2018 Aug 17;22(1):193. doi: 10.1186/s13054-018-2124-8.

Intravenous ivabradine versus placebo in patients with low cardiac output syndrome treated by dobutamine after elective coronary artery bypass surgery: a phase 2 exploratory randomized controlled trial.

Author information

Critical Care Medicine, CMC Ambroise Paré, Neuilly-sur-Seine, France.
Anesthesiology and Critical Care Medicine, Hôpital de la Pitié-Salpétrière, AP-HP, and Université Pierre et Marie Curie, Paris, France.
Anesthesiology and Critical Care Medicine, Institut Mutualiste Monsouris, Paris, France.
Anesthesiology and Critical Care Medicine, Centre Cardiologique du Nord, Saint-Denis, France.
Institut de Recherches Internationales Servier, Suresnes, France.
Anesthesiology and Critical Care Medicine Department, Hôpital Européen Georges Pompidou, AP-HP, and Université Paris Descartes-Sorbonne Paris Cité, Paris, France.



Low cardiac output syndrome (LCOS) is a severe condition which can occur after cardiac surgery, especially among patients with pre-existing left ventricular dysfunction. Dobutamine, its first-line treatment, is associated with sinus tachycardia. This study aims to assess the ability of intravenous ivabradine to decrease sinus tachycardia associated with dobutamine infused for LCOS after coronary artery bypass graft (CABG) surgery.


In a phase 2, multi-center, single-blind, randomized controlled trial, patients with left ventricular ejection fraction below 40% presenting sinus tachycardia of at least 100 beats per minute (bpm) following dobutamine infusion for LCOS after CABG surgery received either intravenous ivabradine or placebo (three ivabradine for one placebo). Treatment lasted until dobutamine weaning or up to 48 h. The primary endpoint was the proportion of patients achieving a heart rate (HR) in the 80- to 90-bpm range. Secondary endpoints were invasive and non-invasive hemodynamic parameters and arrhythmia events.


Nineteen patients were included. More patients reached the primary endpoint in the ivabradine than in the placebo group (13 (93%) versus 2 (40%); P = 0.04). Median times to reach target HR were 1.0 h in the ivabradine group and 5.7 h in the placebo group. Ivabradine decreased HR (112 to 86 bpm, P <0.001) while increasing cardiac index (P = 0.02), stroke volume (P <0.001), and systolic blood pressure (P = 0.03). In the placebo group, these parameters remained unchanged from baseline. In the ivabradine group, five patients (36%) developed atrial fibrillation (AF) and one (7%) was discontinued for sustained AF; two (14%) were discontinued for bradycardia.


Intravenous ivabradine achieved effective and rapid correction of sinus tachycardia in patients who received dobutamine for LCOS after CABG surgery. Simultaneously, stroke volume and systolic blood pressure increased, suggesting a beneficial effect of this treatment on tissue perfusion.


European Clinical Trials Database: EudraCT 2009-018175-14 . Registered February 2, 2010.


Cardiac surgery; Cardiogenic shock; Coronary artery bypass graft; Dobutamine; Low cardiac output syndrome; Postoperative atrial fibrillation; Sinus tachycardia; Systolic heart failure

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