4. DISCUSSION
Our findings suggest that use of liraglutide in AF patients was associated with lower risk of all-cause mortality after controlling for comorbidities, cardiovascular medications, diabetic medications, and cardiovascular procedures. With liraglutide, there was a trend towards lower risk of ischemic stroke, hemorrhagic stroke, acute heart failure episode, and acute coronary syndrome episode in these patients, but did not reach statistical significance.
Liraglutide is one of the GLP-1 receptor agonists that has been utilized for treatment of diabetes mellitus and associated with a reduced risk of major cardiovascular outcomes. In the LEADER trial, diabetic patients with increased cardiovascular risk were randomized to liraglutide or placebo and were found to have significantly lower cardiovascular-related and all-cause mortality with liraglutide [1]. However, in patients with reduced ejection fraction, the data has been controversial. In the FIGHT trial there was no significant difference in the number of deaths or heart failure-related hospitalization in patients with reduced left ventricular function on the medication [3]. The LIVE trial found that in patients with reduced left ventricular ejection fraction, liraglutide use was associated with no major change in LVEF, increased heart rate variability, and serious cardiac events including cardiovascular related death, ventricular tachycardia, acute coronary syndrome, worsening heart failure, and atrial fibrillation [4]. There have been reports of increased heart rate with liraglutide possibly due to a direct effect on the sinoatrial node [5,6].
Furthermore, pooled data analysis of multiple trials demonstrated that in diabetic patients, GLP-1 agonists were not associated with increased incidence of atrial fibrillation when compared to placebo [7]. In addition, a meta-analysis of 34 trials found that GLP-1 receptor agonists did not increase the risk of atrial fibrillation [8]. Currently, there have been no studies examining the effect of liraglutide or GLP-1 agonists in atrial fibrillation patients and their outcomes.
Our study provides large retrospective data on the effect of liraglutide on AF patients and found that liraglutide use is associated with lower mortality risk (HR 0.67, 95% CI 0.631 – 0.711, p < 0.001). The mechanism of GLP-1 agonist benefits on atrial fibrillation is still not fully understood. In canine atrial fibrillation models, liraglutide had electrophysiologic effects such as suppressing atrial fibrillation inducibility and conduction velocity. This may contribute to the decreased mortality associated with these patients due to decreased burden of AF. Further studies are needed to examine the mechanism of liraglutide’s possible protective effect on atrial fibrillation patients.
There are several limitations to this study. First, these results are based on aggregate data of ICD and CPT codes. We attempted to address these issues by utilizing time constraints to ensure patients had diagnoses and medications for at least one month. In addition, the TriNetX data platform provided the aggregate data and statistical analysis. This limited our abilities to utilize other analytical methods. Lastly, we were unable to control for social factors. Liraglutide may not be as accessible for patients with lower socioeconomic status which may introduce a potential bias. Despite these limitations, this study provides a new potential benefit of liraglutide in AF patients by reducing mortality, as prospective trials on this cohort are lacking.
In 16,214 atrial fibrillation patients, use of liraglutide was associated with lower risk of all-cause mortality. Further studies should be conducted to provide additional evidence for the benefit of liraglutide in patients with atrial fibrillation.