Glucagon-like Peptide-1 Agonists Reduce Cardiovascular Events in Cancer Patients on Immune Checkpoint Inhibitors

Cho-Han Chiang; Junmin Song; Kuan-Yu Chi; Yu-Cheng Chang; Nutchapon Xanthavanij; Yu Chang; Yuan Ping Hsia; Cho-Hung Chiang; Azin Ghamari; Kerry L Reynolds; Shuwen Lin; Xiaocao Haze Xu; Tomas G Neilan

doi:10.1016/j.ejca.2024.115170

Glucagon-like Peptide-1 Agonists Reduce Cardiovascular Events in Cancer Patients on Immune Checkpoint Inhibitors

Eur J Cancer. 2024 Dec 11:216:115170. doi: 10.1016/j.ejca.2024.115170. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, USA. Electronic address: chohan.chiang@mah.harvard.edu.
² Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
³ Department of Medicine, Danbury Hospital, Danbury, CT, USA.
⁴ Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, USA.
⁵ Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁶ Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan. Electronic address: ustwhealth.datascience.group@gmail.com.
⁷ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁸ Cardiovascular Imaging Research Center, Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Department of Oncology, Montefiore Medical Center, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA.
¹¹ Division of Hematology and Oncology, Department of Medicine, University of Vermont Medical Center, Burlington, VT, USA.

PMID: 39709670
DOI: 10.1016/j.ejca.2024.115170

Abstract

Background: Immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE). Glucagon-like peptide-1 agonists (GLP1a), initially developed for type 2 diabetes mellitus (T2DM), have shown promising results in reducing cardiovascular events. We aimed to investigate the effect of GLP1a on cardiovascular events in patients receiving ICIs.

Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX database. We identified adults with cancer and T2DM who received ICIs between April 2013 and May 2023. The primary efficacy outcome was incident MACE, defined as a composite of myocardial infarction, need for coronary revascularization, heart failure, ischemic stroke, and cardiac arrest. The secondary efficacy outcomes were the individual components of MACE as well as myocarditis and pericarditis. Safety outcomes included the occurrence of immune-related adverse events, serious adverse events related to GLP1a use, and all-cause mortality.

Results: We identified 7651 patients eligible for inclusion, among which 479 received GLP1a and 7172 received non-GLP1a diabetes medications. After matching (469 patients each), baseline characteristics were well-balanced. Over a median 12-month follow-up, the GLP1a cohort had a significantly lower MACE incidence than the non-GLP1a cohort (9.0 vs. 17.1 events per 100 patient-years) with a 54 % lower risk of MACE (Hazard ratio (HR),0.46 [95 % CI: 0.32-0.67]). There were reductions in myocardial infarction or need for coronary revascularization, heart failure, and all-cause mortality, with no differences in other cardiovascular events. GLP1a use did not increase risk of adverse events, including pancreatitis, biliary disease, bowel obstruction, gastroparesis, and immune-related adverse events.

Conclusion: GLP1a use in cancer patients with T2DM receiving ICIs was associated with reduced MACE and all-cause mortality without an increased risk in serious adverse events.

Keywords: Cardiovascular event; Glucagon-like peptide-1 agonists; Immune checkpoint inhibitor; Immune-related adverse event.