Glucagon-Like Peptide-1 Agonist vs. Placebo and Pulmonary Decline After Open-Heart Surgery: A Substudy of the GLORIOUS Randomised Clinical Trial.

BACKGROUND: Postoperative pulmonary decline is an established complication of open-heart surgery extending beyond the immediate postoperative phase. Inflammation-mediated lung damage and ischaemia-reperfusion injury secondary to extracorporeal circulation is a proposed pathophysiological driver. GLP-1 receptor agonists (GLP-1RA) have emerged as promising protective agents in this setting. AIM: Investigate whether infusion of the GLP-1RA, exenatide during cardiopulmonary bypass and weaning thereof, can mitigate the decline in diffusing capacity and ventilatory performance 3 months postoperative, compared to placebo. METHODS: In this predefined explorative substudy of the randomised, clinical GLORIOUS trial, 878 adult patients undergoing non-emergent coronary artery bypass grafting (CABG) and/or surgical aortic valve replacement (SAVR) were randomised to a continuous infusion of the GLP-1RA, exenatide or placebo during cardiopulmonary bypass, extending into the early postoperative period. Diffusing capacity of the lung for carbon monoxide (DLCO) and ventilatory performance (FEV/FVC) were measured preoperatively and 3 months postoperatively. RESULTS: Median DLCO (% predicted corrected) declined from 80% preoperative to 72% 3 months postoperative, corresponding to a -7.7 percentage point (pp) difference (95% CI 6.2 to 9.1; p < 0.001). FEV/FVC declined from 0.75 preoperative to 0.73 postoperative, corresponding to a -1.6 difference (95% CI 1.0 to 2.1; p < 0.001). However, there were no significant differences in decline between the exenatide and placebo groups (all p > 0.3). Findings were consistent across subgroup analyses. CONCLUSION: While both diffusing capacity and ventilatory performance exhibited a mild-to-moderate decline 3 months after open-heart surgery, the GLP-1RA exenatide did not mitigate this decline compared with placebo. EDITORIAL COMMENT: Pulmonary dysfunction is one of the most common complications to open-heart surgery. The present study confirms a decline in diffusing capacity of the lung for carbon monoxide (DLCO) and in ventilatory performance measured as FEV/FVC at 3 months postoperatively compared to preoperative measurements. Infusion of GLP-1 receptor antagonist during cardiopulmonary bypass and weaning did not mitigate the pulmonary decline compared to placebo.