Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass - LEVO-CTS

Mar 19, 2017
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Presenter/Author:
John H. Alexander, MD, FACC
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Tenax Therapeutics
Date Presented:
03/19/2017
Date Published:
03/19/2017
Original Posted Date:
03/19/2017
References

Contribution To Literature:

The LEVO-CTS trial failed to show that levosimendan improved outcomes compared with placebo.

Description:

The goal of the trial was to evaluate levosimendan compared with placebo among patients undergoing cardiac surgery with cardiopulmonary bypass.


Study Design

  • Randomized
  • Parallel
  • Double-blind
  • Placebo

Patients undergoing cardiac surgery with the use of cardiopulmonary bypass were randomized to infusion of levosimendan 0.2 µg/kg/min for 1 hour, then 0.1 µg/kg/min for 23 hours (n = 442) versus placebo infusion (n = 440). The infusion was started before surgery.

  • Total number of enrollees: 882
  • Duration of follow-up: 90 days
  • Mean patient age: 65 years
  • Percentage female: 19%
  • Percentage with diabetes: 50%

Inclusion criteria:

  • Patient ≥18 years of age undergoing cardiac surgery with the use of cardiopulmonary bypass. Cardiac surgery procedures could include coronary artery bypass grafting (CABG), CABG with aortic or mitral valve surgery, or any combination.
  • Left ventricular ejection fraction (LVEF) ≤35% 60 days before surgery

Exclusion criteria:

  • Restrictive or obstructive cardiomyopathy, constrictive pericarditis, restrictive pericarditis, or pericardial tamponade
  • Systemic infection
  • Dialysis
  • Weight ≥170 kg
  • Systolic blood pressure <90 mm Hg or heart rate >120 bpm
  • Hemoglobin <8.0
  • Potassium <3.5 or >5.5
  • Mechanical assist device
  • Liver disease
  • Immunocompromised
  • Pregnancy
  • History of torsade de pointes

Other salient features/characteristics:

  • Cardiac index: 2.86 L/min/m2 for levosimendan vs. 2.68 L/min/m2 for placebo (p < 0.0001)

Principal Findings:

The first primary outcome, incidence of short-term death, MI, dialysis, or mechanical assist device, occurred in 24.5% of the levosimendan group versus 24.5% of the placebo group (p = 0.98).

The second primary outcome, incidence of death or mechanical assist device, occurred in 13.1% of the levosimendan group versus 11.4% of the placebo group (p = 0.45).

Secondary outcomes:

  • Death at 30 days: 3.5% for levosimendan vs. 4.5% for placebo
  • Any serious adverse event: 18.0% for levosimendan vs. 16.6% for placebo

Interpretation:

Among patients with low LVEF undergoing cardiac surgery with cardiopulmonary bypass, levosimendan was not beneficial. Levosimendan did not improve either of the two co-primary endpoints compared with placebo. Levosimendan was associated with a modest improvement in cardiac index; however, the relatively preserved cardiac index in the placebo group may have limited any opportunity to detect a difference between treatment groups.

References:

Mehta RH, Leimberger JD, van Diepen S, et al., on behalf of the LEVO-CTS Investigators. Levosimendan in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery. N Engl J Med 2017;Mar 19:[Epub ahead of print].

Presented by Dr. John H. Alexander at the American College of Cardiology Annual Scientific Session (ACC 2017), Washington, DC, March 19, 2017.

Keywords: ACC17, ACC Annual Scientific Session, Aortic Valve, Cardiac Output, Low, Cardiac Surgical Procedures, Cardiopulmonary Bypass, Coronary Artery Bypass, Cost-Benefit Analysis, Dialysis, Hydrazones, Mitral Valve, Myocardial Infarction, Pyridazines, Renal Replacement Therapy, Stroke Volume, Ventricular Dysfunction, Left


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