Levosimendan Disappoints Again in Low-LVEF CABG: LICORN

August 10, 2017

PARIS, FRANCE — Patients with low LV ejection fraction about to undergo CABG surgery who received a 24-hour infusion of levosimendan (Simdax, Orion) later showed the signs of low cardiac-output syndrome about as often as those who received placebo in a small randomized trial[1].

That finding, from the Levosimendan in Coronary Artery Revascularization (LICORN) trial, published August 8, 2017 in the Journal of the American Medical Association, was reminiscent of the recently reported, randomized LEVO-CTS study, reported recently by theheart.org | Medscape Cardiology from the American College of Cardiology 2017 Scientific Sessions.

In that earlier trial, which was simultaneously published in the New England Journal of Medicine[2], patients similar to those in LICORN who received the calcium-sensitizing inotropic agent failed to show a benefit in a primary end point that included some elements of the low cardiac-output syndrome but also short-term MI and death.

LICORN randomized 335 patients with an LVEF <40% who were slated for CABG (isolated in 74%) to receive double-blind levosimendan (0.1 μg/kg/min) or placebo in a 24-hour infusion at 13 centers in France. They were followed for 6 months after surgery, report the authors, led by Dr Bernard Cholley (Hôpital Européen Georges-Pompidou, Paris, France).

The primary end point, met by 52% who received levosimendan and 61% of controls, was a composite of catecholamine infusion 48 hours after the start of randomized therapy, need for or failure to wean from a left ventricular mechanical assist device by 96 hours, or dialysis at any time after surgery. The end point was designed to reflect several important hallmarks of low cardiac-output syndrome.

The adjusted -8% (95% CI -17% to 3%) absolute risk difference between the two primary-end-point outcomes by intention to treat wasn't significant (P=0.15), nor was the absolute risk difference of -8% (95% CI -18% to 3%, P=0.14) in a per-protocol analysis.

There were no significant differences in secondary end points that included mortality in-hospital and at 1 and 6 months; components of the primary end point; number of days on ventricular assist support or on dialysis; and number of out-of-hospital days.

Nor were there significant differences in adverse events, including hypotension or atrial fibrillation.

Levosimendan was infused without a preceding bolus dose "to avoid an excess of vasodilatation in this fragile population," the authors observe. "This might explain, in part, the minimal effect of levosimendan observed in this study."

Cholley discloses receiving a lecture honorarium from Orion Pharma; disclosures for the coauthors are listed in the paper.

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