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.