Efficacy of the Glucagon-Like Peptide-1 Agonist Exenatide in Patients Undergoing CABG or Aortic Valve Replacement: A Randomized Double-Blind Clinical Trial

Abstract

Background: GLP-1 (glucagon-like peptide-1) agonists have been proven beneficial in reducing the risk of and injury associated with several cardiovascular diseases. The efficacy in cardiopulmonary bypass-assisted cardiac surgery is unknown. This trial aimed to investigate the efficacy of an infusion of the GLP-1 agonist exenatide during and after open-heart surgery in reducing the risk of death and major organ failure.

Methods: Randomized, double-blinded, 2-by-2 factorial design, single-center clinical trial, also including liberal (FiO₂ of 100%) or restrictive (FiO₂ of 50%) oxygenation during and after bypass. The present article presents the results of the exenatide intervention. We included adult patients undergoing elective cardiopulmonary bypass-assisted coronary artery bypass grafting or aortic valve replacement. Patients were predominantly low risk. The intervention was an infusion of 17.4 µg of exenatide or placebo during cardiopulmonary bypass and the first hour after weaning thereof. The main outcome was time to a composite end point consisting of death, stroke, renal failure requiring dialysis, or new/worsening heart failure during follow-up. Secondary end points included occurrence of prespecified adverse events.

Results: A total of 1389 patients were included in the analyses. Within a follow-up period of a median of 5.9 years (min-max; 2.5-8.3 years), 170 (24%) patients in the exenatide group and 165 (24%) patients experienced a primary end point. We found no difference in time to the first event between patients randomized to FiO₂ 50% versus FiO₂ 100% (hazard ratio, 1.0 [95% CI, 0.83-1.3]; P=0.80). We found no significant difference in rates of adverse events between the 2 groups.

Conclusions: Exenatide during cardiopulmonary bypass and weaning thereof did not significantly reduce the incidence of death, stroke, renal failure, or new/worsening heart failure in patients undergoing coronary artery bypass grafting and aortic valve replacement.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02673931.

Keywords: aortic valve stenosis; coronary artery bypass; heart failure; humans; outcome.