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

ABSTRACT 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 1 /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 &lt; 0.001). FEV 1 /FVC declined from 0.75 preoperative to 0.73 postoperative, corresponding to a −1.6 difference (95% CI 1.0 to 2.1; p &lt; 0.001). However, there were no significant differences in decline between the exenatide and placebo groups (all p &gt; 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 1 /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.