On November 18, at the American Heart Association (AHA) 100th Annual Meeting 2024, the safety of glucagon-like peptide-1 receptor (GLP-1R) agonists in heart failure and chronic kidney disease (CKD) patients was discussed. GLP-1R agonists are cardioprotective in type 2 diabetes (T2D) patients, but data on other patient populations is still limited. According to GlobalData, label expansions for the use of GLP-1R agonists in cardiovascular comorbidities may open up the possibility of partial reimbursement.
Real-world data on GLP-1R agonists’ safety in heart failure and CKD patients was investigated using the TriNetX Research Network. TriNetX is a global, collaborative, real-world database for life science and healthcare where drug developers and researchers can download and analyse data sets. For the purpose of the presented study, two cohorts of patients from January 2005 to April 2023 were examined for 12 months. The first cohort included patients with heart failure and CKD who were taking GLP-1R agonist medications, while the control cohort included patients with heart failure and CKD who were taking a placebo. More than one million patients were analysed in total, with the average age being around 68.4 years.
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The propensity score-matched (PSM) analysis took into account age, gender, race, hypertension, diabetes mellitus, CKD, smoking status, haemoglobin level, low-density lipoprotein (LDL) level, left ventricular ejection fraction, and various drugs including angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), beta-blockers, aldosterone receptor antagonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and statins. The analysis showed that at one year of follow-up, heart failure and CKD patients taking GLP-1R agonists had a significantly lower risk of all-cause mortality, major adverse cardiovascular events, acute myocardial infarction, and ischemic and hemorrhagic stroke compared to control. This suggests that the cardioprotective properties of GLP-1R agonists are transferrable to the heart failure and CKD patient population, as well as the T2D population.
Another presentation from November 18 adds to the evidence of using GLP-1R agonists for cardiovascular health benefits, suggesting a reduction in atrial fibrillation incidence in obese patients. At one year from hospitalization following a primary diagnosis of heart failure exacerbation, a Cox regression analysis revealed that GLP-1R agonist-treated patients with obesity had a significantly lower incidence of atrial fibrillation compared to untreated patients (9.3% versus 16% incidence, respectively). Thus, GLP-1R agonists lower the incidence of atrial fibrillation at one year in obese patients who have been hospitalized for heart failure. However, the results differed in non-obese individuals and patients with diabetes without obesity. In those populations, GLP-1R agonist use was not associated with a statistically significant reduction in the incidence of atrial fibrillation (14.5% incidence was observed in the treated group versus 19.5% in the untreated group).
Key opinion leaders (KOLs) interviewed by GlobalData noted: “We have trials demonstrating that the use of GLP-1R agonists in patients with very high cardiovascular risk reduces cardiovascular events. This is a strong argument for reimbursement…I think that the GLP-1R agonists, or tirzepatide, will soon enter the guidelines for the treatment of heart failure or sleep apnoea. So the increase in trials showing an impact on the prognosis and the outcomes of these important comorbidities will produce increased attention to the problem of obesity in patients with these comorbidities. The inclusion of the GLP-1R agonists or other drugs in the treatment algorithm of heart failure, of sleep apnoea, will increase the demand for these drugs, the importance of the cardiometabolic aspects of these drugs, and maybe open the door for partial reimbursement…for a particular fraction of the patients, those with comorbidities.”
Companies developing GLP-1R agonists will likely continue to explore new therapeutic areas in which this class of drugs may have some potential for market approval and label expansion. Consequently, as interest in GLP-1R agonists increases and their benefits become even more apparent, they may be granted partial reimbursement for specific patient populations.
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