A major clinical trial has found that the use of exenatide, a glucagon-like peptide-1 (GLP-1) analog medication, during heart surgeries involving cardiopulmonary bypass did not provide significant benefits in reducing complications or improving patient outcomes. The GLORIOUS trial, presented at the American Heart Association's Scientific Sessions 2024 in Chicago, challenges previous assumptions about the potential protective effects of exenatide in cardiac surgical procedures.
The study, conducted at a heart center in Denmark between 2016 and 2021, involved approximately 1,400 adult patients undergoing coronary bypass grafting and/or surgical aortic valve replacement. Participants were randomly assigned to receive either a six-hour and 15-minute infusion of exenatide or a placebo prior to surgery. The trial's findings revealed no significant differences in outcomes between the two groups over an average follow-up period of nearly six years.
Specifically, the study found that 14% of patients who received exenatide died during the follow-up period, compared to 13% in the placebo group. The incidence of stroke was 5.8% in the exenatide group versus 4.8% in the placebo group. New or worsening heart failure after surgery occurred in 9.8% of exenatide recipients compared to 10% in the placebo group. Acute kidney injury during the initial hospital admission was observed in 4.8% of the exenatide group versus 5.3% in the placebo group.
These results are particularly significant given the widespread use of cardiopulmonary bypass in heart surgeries and the ongoing search for methods to reduce associated risks. Cardiopulmonary bypass, while essential for many cardiac procedures, carries inherent risks including death, stroke, kidney failure, and heart failure. The GLORIOUS trial's findings underscore the complexity of addressing these risks and the need for continued research in perioperative care for cardiac surgery patients.
Dr. Sebastian Wiberg, the study's lead investigator and an anesthesiologist at The Heart Centre, Copenhagen University Hospital Rigshospitalet, emphasized the importance of these findings in the context of limited evidence for perioperative treatment in cardiac surgery. He noted, '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 optimize patient health during and after bypass surgery.'
While the results may be disappointing for those hoping exenatide would offer protective benefits, they provide valuable insights into the limitations of current approaches. The study's outcomes suggest that the potential organ-protective effects of exenatide, previously indicated in some research, may not translate to significant clinical benefits in the context of cardiac surgery with cardiopulmonary bypass.
However, it's important to note the study's limitations. The trial assessed the effects of a single treatment with exenatide over a relatively brief administration period at one heart center in Denmark. As such, the results may not be generalizable to other medications, different patient populations, or alternative dosing regimens. Dr. Wiberg suggested that different GLP-1 analogs, longer administration periods, or larger doses might potentially yield different results.
The GLORIOUS trial's findings have significant implications for the field of cardiac surgery and highlight the ongoing challenges in improving outcomes for patients undergoing these complex procedures. As researchers continue to explore potential interventions, this study underscores the importance of rigorous clinical trials in evaluating the efficacy of proposed treatments.
For patients and healthcare providers, these results emphasize the need for continued vigilance and comprehensive care strategies in cardiac surgery. While the search for effective interventions to reduce complications continues, the focus remains on optimizing current best practices and individualized patient care to ensure the best possible outcomes for those undergoing cardiac surgical procedures.
