Intravenous exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, did not significantly reduce the risk of death, stroke, or organ failure in patients undergoing cardiopulmonary bypass-assisted cardiac surgery, according to results from the GLORIOUS trial presented at the American Heart Association (AHA) Scientific Sessions 2024.
The randomized, double-blind, placebo-controlled trial enrolled approximately 1400 adults in Denmark scheduled for elective or subacute coronary bypass grafting or surgical aortic valve replacement between February 2016 and December 2021. Patients were randomized to receive either a 6-hour and 15-minute intravenous infusion of 17.4 μg exenatide or a placebo, initiated at the time of anesthesia before surgery.
Trial Design and Patient Population
The average age of participants was 68 years, with 17% being female and 98% self-identifying as White. The primary objective of the GLORIOUS trial was to determine if exenatide could reduce complications during and after cardiac surgery involving cardiopulmonary bypass.
Key Findings
Over an average follow-up period of 5.9 years, the study found no significant differences between the exenatide and placebo groups. Specifically, 14% of patients receiving exenatide died during the follow-up, compared to 13% in the placebo group. Stroke occurred in 5.8% of the exenatide cohort versus 4.8% in the placebo cohort. New or worsening heart failure was observed in 9.8% of the exenatide group and 10% of the placebo group. Acute kidney injury during the initial hospital admission occurred in 4.8% of the exenatide group, compared to 5.3% in the placebo group.
Expert Commentary
Sebastian Wiberg, MD, PhD, an anesthesiologist at The Heart Centre, Copenhagen University Hospital Rigshospitalet, noted the limitations of the trial, including its focus on a single heart center and the brief period of exenatide administration. He suggested that different GLP-1s, a longer administration period, or a larger dose might yield different results. "We had hoped exenatide might protect patients from developing heart failure or other common complications after heart bypass surgery, however, the results suggest that this GLP-1 analog does not offer significant benefits," Wiberg stated.
Wiberg also emphasized the "urgent need" for further clinical trials to identify methods to optimize patient outcomes during and after cardiac surgery, highlighting a significant knowledge gap in supporting patients on bypass during surgery.
Implications for Clinical Practice
The GLORIOUS trial's findings indicate that intravenous exenatide does not provide a preventive effect on organ injury in patients undergoing cardiopulmonary bypass-assisted cardiac surgery. These results contribute important insights into the complex setting of cardiac surgery and underscore the need for continued research to improve patient outcomes.
