Presented at AHA Scientific Sessions 2024 as a Research Abstract.This summary does not represent the original research, nor is it intended to replace the original research. Content Disclaimer

 

The study included 1,389 adults scheduled for elective or subacute cardiopulmonary bypass-assisted CABG and, or a surgical aortic valve replacement.
 

The average age was 68 years & 17% were female.
 

30% had pre-existing heart disease, 16% with heart failure, 20% had a history of myocardial infarction, and 9% had had a prior stroke.

Study Design
 

The GLORIOUS trial was a multicenter, randomised, double-masked, placebo-controlled study conducted at a single heart centre in Denmark between February 2016 and December 2021. 

The participants were randomised to receive either a six-hour, 15-minute infusion of exenatide (17.4 µg) or a placebo initiated at the time of anaesthesia before surgery. 

• Renal failure requiring replacement therapy

• Stroke (neurological dysfunction >24 hours)

• New or worsening heart failure requiring mechanical circulatory support, prolonged inotropic support, or reoperation
   

Secondary outcomes included the incidence of complications including:

• Surgical site infections requiring prolonged antibiotics or surgical debridement

• Significant reductions in left ventricular ejection fraction (LVEF)

• Post-surgical myocardial infarction (type 5)

• Cardiovascular-related hospital readmissions.

Over an average follow-up period of 5.9 years, no significant differences were observed between the exenatide and placebo groups across key outcomes:

The following were recorded:

Mortality: there was a 14% mortality rate in the exenatide group vs. 13% in the placebo group

Stroke: 5.8%  of the participants in the exenatide group vs. 4.8% in the placebo group experienced a stroke

Heart Failure: 9.8% of the exenatide group experienced new or worsening heart failure vs. 10% in the placebo group

Acute Kidney Injury: 4.8% in the exenatide group vs. 5.3% in the placebo group were diagnosed with AKI

In the separate arm of the study, a restrictive oxygenation strategy during cardiopulmonary bypass-assisted coronary bypass grafting and/or SAVR and weaning of cardiopulmonary bypass in adult patients did not reduce mortality or morbidity from renal failure, stroke or heart failure.
 

Participants were followed for a median of 5.9 years until a total of 323 events had occurred 

No significant difference between the two treatment groups was recorded.

The GLORIOUS trial demonstrated that a single, short-duration infusion of exenatide did not significantly reduce mortality or prevent complications such as ischemic injury, renal failure, or heart failure in patients undergoing cardiopulmonary bypass. These findings underscore the limitations of GLP-1 agonists in this setting and the necessity for further research into alternative treatment strategies.

The study also highlights the need for trials evaluating different GLP-1 analogues, extended treatment durations, or higher dosing regimens to determine their potential protective effects during open-heart surgery.

In an interview conducted by AHA Newsroom, investigator Sebastian Wiberg, M.D., PhD, an anaesthesiologist at The Heart Centre, Copenhagen University Hospital Rigshospitalet in Copenhagen, Denmark, commented:
 

"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. Of note, these findings provide important insights into what does and doesn't work in the complex setting of cardiac surgery. There is still a big gap in knowledge about how to best support patients on bypass during surgery, and there is an urgent need for more clinical trials to find ways to optimise patient health during and after bypass surgery."

AHA Scientific Sessions 2024 News Release
 

16 Nov 2024 | AHA Newsroom | Exenatide, a GLP-1 analog, by IV during cardiac surgery did not reduce organ injury or death American Heart Association Scientific Sessions 2024, Abstract 4170664

Funding