Efficacy of the glucagon-like peptide-1 agonist Exenatide in patients undergoing coronary artery bypass grafting or aortic valve replacement – a randomized double-blind clinical trial

Importance Glucagon-like peptide-1 (GLP-1) agonists have been proven beneficial in reducing risk of and injury associated with several cardiovascular diseases. The efficacy in cardiopulmonary bypass (CPB)-assisted cardiac surgery is unknown. Objective This trial aimed to investigate the efficacy of an infusion of the GLP-1 antagonist Exenatide during and after open heart surgery in reducing risk of death and major organ failure. Design Randomized, double-blinded, 2-by-2 factorial design, clinical trial, also including liberal (FiO2 of 100%) or restrictive (FiO2 of 50%) oxygenation during and after bypass. The present paper presents the results of the Exenatide intervention. Setting Single site, tertiary heart center. Participants Adult patients undergoing elective cardiopulmonary bypass-assisted coronary artery bypass grafting and/or aortic valve replacement. Intervention Infusion of 17.4 µg og Exenatide or placebo during cardiopulmonary bypass and the first hour after weaning thereof Main outcomes The main outcome was time to a composite endpoint consisting of death, stroke, renal failure requiring dialysis, or new/worsening heart failure during follow-up. Secondary endpoints included occurrence of prespecified adverse events. Results A total of 1389 patients were included in the analyses. Within a follow-up period of median of 5.9 years (min – max; 2.5 – 8.3 years), 170 patients (24%) in the Exenatide group and 165 patients (24%) experienced a primary endpoint. We found no difference in time to first event between patients randomized to FiO 2 50% versus FiO 2 100% (HR 1.0 [95%CI 0.83 – 1.3], p = 0.80). We found no significant difference in rates of adverse events between the two groups. Conclusions and Relevance 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/or aortic valve replacement. Trial registration Danish Medicines Agency: Protocol no. HJE-PHARMA-001, EudraCT no. 2015-003050-41, 2 nd of October 2015 Local Ethics Committee “Videnskabsetisk komité C, Region Hovedstaden”: No. H-15010562 www.clinicaltrials.gov : ID no. NCT0267393 Key Points Question Is a single dose of Exenatide effectively reducing risk of death or major organ injury in patients undergoing cardiopulmonary bypass (CPB)-assisted cardiac surgery? Findings 1400 patients undergoing coronary artery bypass grafting and/or aortic valve replacement were randomized to 17,4 µg of Exenatide or placebo during CPB and the first hour after weaning. The hazard ratio (95%CI) for time to the first occurring composite endpoint consisting of death, stroke, renal failure requiring dialysis, and new/worsening heart failure was 1.0 (0.83 – 1.3). Meaning Exenatide infusion during CPB-assisted cardiac surgery does not improve outcomes.