November 17, 2024
3 min read
Key takeaways:
- Exenatide, an intravenous GLP-1 receptor agonist, did not significantly reduce the incidence of death, stroke, heart failure, or renal failure when compared to placebo after cardiopulmonary bypass-assisted heart surgery.
- Both restrictive and liberal oxygenation strategies produced similar clinical outcomes, showing no notable differences between the two approaches.
CHICAGO — The findings of the GLORIOUS trial revealed that exenatide failed to enhance clinical outcomes for patients undergoing heart surgery, as presented by Sebastian Wiberg, MD, PhD, clinical associate professor of anesthesiology at The Heart Centre, Copenhagen University Hospital Rigshospitalet in Copenhagen, Denmark.
The study, which enrolled 1,389 patients with an average age of 68 years—of which 17% were women and 15% had type 2 diabetes—was unveiled at the American Heart Association Scientific Sessions.
“Application of CPB is known to cause organ injury, which is associated with morbidity and death,” Wiberg noted. He elaborated on the complex etiology of organ injury, which encompasses multiple pathways, including cellular damage resulting from oxidative stress, ischemia-reperfusion injury due to flow disturbances, and inflammatory responses triggered by mechanical stress. “Back in 2014, when this trial was designed, animal studies suggested that GLP-1 agonists could mitigate several neurodegenerative conditions,” he added.
Wiberg stated that, in animal models, GLP-1 agonists significantly reduced the final infarct size in instances of stroke and myocardial infarction. Similar positive outcomes were observed in humans, particularly in patients suffering from ST-elevation myocardial infarction when exenatide was administered. Due to its safety profile in critically ill patients, researchers theorized that administering an infusion of 17.4 µg of exenatide over approximately 6 hours could lower mortality and severe organ injury rates during CPB-assisted CABG and/or AVR procedures.
When asked how the trial might differ if designed in the present, Wiberg mentioned that they would likely utilize a more contemporary GLP-1 receptor agonist, such as semaglutide (Ozempic/Wegovy, Novo Nordisk).
Exenatide vs. placebo
During surgical procedures, patients who received exenatide exhibited lower blood glucose levels, according to Wiberg’s presentation.
Significantly, there were no meaningful differences in adverse events between groups, with rates of hypoglycemia remaining extremely low—only two patients in the exenatide group experienced this within 12 hours post-surgery, and none in the placebo group.
Furthermore, in analysis of predefined subgroups, exenatide showed a slight preference for patients with a history of stroke; however, Wiberg cautioned that this finding should be approached with caution as exploratory.
The analysis also confirmed that there was no difference between groups regarding the first occurrence of a primary endpoint event within a 180-day follow-up period (HR = 0.99; 95% CI, 0.72-1.4). “In adult patients undergoing CPB-assisted elective or subacute CABG and/or AVR, a perioperative infusion with the GLP-1 agonist exenatide did not produce significant reductions in mortality or morbidity caused by renal failure, stroke, or heart failure,” Wiberg concluded.
Oxygenation strategies
In evaluating oxygenation strategies, the partial pressure of oxygen was significantly higher in the liberal-strategy group (P P = .92). Additionally, Wiberg noted that there was no interaction between the effects of exenatide and the chosen oxygenation strategies (P for interaction = .4).
The ongoing GLORIOUS II trial, which investigates four different interventions in patients undergoing CPB-assisted CABG and/or AVR, is projected to be completed by 2027.
Published by:
Collapse
Source:
Wiberg S, et al. LBS.04: From intervention to prevention: Advances in coronary and valvular heart disease. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2024; Chicago.
Disclosures:
Sandner and Wiberg report no relevant financial disclosures.
How might the outcomes of the GLORIOUS trial influence future research on GLP-1 receptor agonists in cardiac surgery?
**Interview with Dr. Sebastian Wiberg on the GLORIOUS Trial Findings**
**Interviewer:** Good afternoon, Dr. Wiberg. Thank you for joining us today to discuss the findings of the recent GLORIOUS trial. To start, can you summarize the key outcomes of the study?
**Dr. Wiberg:** Absolutely. The GLORIOUS trial aimed to assess the effect of exenatide, a GLP-1 receptor agonist, on clinical outcomes for patients undergoing cardiopulmonary bypass-assisted heart surgery. Unfortunately, we found that exenatide did not significantly reduce the rates of death, stroke, heart failure, or renal failure when compared to a placebo. Moreover, our study showed that both restrictive and liberal oxygenation strategies resulted in similar clinical outcomes, indicating no major advantages of one approach over the other.
**Interviewer:** That’s interesting. You mentioned the study enrolled 1,389 patients. What was the demographic profile of these participants?
**Dr. Wiberg:** The participants had an average age of about 68 years, with 17% being women and around 15% having a diagnosis of type 2 diabetes. This diverse cohort allowed us to examine the effects of exenatide across a fairly representative sample of the population typically undergoing such surgeries.
**Interviewer:** It seems the rationale for using exenatide was based on earlier animal studies. Could you elaborate on those findings?
**Dr. Wiberg:** Certainly. Prior to our trial, animal studies indicated that GLP-1 agonists like exenatide could mitigate strokes and myocardial infarctions by reducing infarct size. These promising preclinical results led us to hypothesize that exenatide could similarly lower mortality and severe organ injury rates during high-risk cardiac procedures in humans.
**Interviewer:** Did you observe any unexpected outcomes during the trial?
**Dr. Wiberg:** One notable observation was that while patients treated with exenatide did experience lower blood glucose levels during surgery, there were no significant differences in adverse events across the groups. The rates of hypoglycemia were extremely low, with only two cases in the exenatide group and none in the placebo group. Additionally, there was a slight preference for exenatide in patients with a history of stroke, but the main endpoints did not show significant benefits.
**Interviewer:** If you were to conduct this trial today, how might your approach differ?
**Dr. Wiberg:** If we were to redesign the trial now, I would consider using a more contemporary GLP-1 receptor agonist, such as semaglutide, which may have different pharmacological properties and potentially better outcomes. The ongoing advancements in pharmacotherapy could provide fresh insights that we couldn’t leverage back in 2014 when we initiated the original trial.
**Interviewer:** Thank you for your insights, Dr. Wiberg. It seems this research has paved the way for further exploration in improving outcomes for patients undergoing heart surgery.
**Dr. Wiberg:** Thank you for having me. It certainly has raised new questions and directions for future research that could enhance recovery processes in this patient demographic.