What are the risks of Glucagon-like peptide-1 (GLP-1) in a person with atrial fibrillation (AFib) and hypovolemia, who also has cardiomyopathy?

From the Guidelines

GLP-1 receptor agonists should be used with extreme caution in patients with atrial fibrillation, volume depletion, and cardiomyopathy, as they may worsen volume depletion and potentially compromise cardiac output. These medications (including semaglutide, liraglutide, dulaglutide, and others) carry several specific risks in this patient population. Volume depletion can be worsened by the gastrointestinal side effects of GLP-1 agonists, which include nausea, vomiting, and diarrhea, potentially exacerbating hypotension and compromising cardiac output in someone with cardiomyopathy, as noted in a study published in Circulation 1. For patients with atrial fibrillation, the potential heart rate effects of GLP-1 agonists could theoretically impact rhythm control, though this is less established.

Key Considerations

• The FIGHT study, which randomized 300 patients with chronic HFrEF and recent HF hospitalization to liraglutide or placebo for 6 months, found that liraglutide had no effect on posthospitalization clinical stability and tended to increase the risk of HF readmission 1.
• A scientific statement from the American Heart Association and the Heart Failure Society of America suggests that GLP-1 receptor agonists may reduce the risk of major adverse cardiovascular events and mortality in the general population of patients with DM, but have had no impact on the risk of HF hospitalization in large RCTs 1.
• Given the lack of evidence of benefit and a trend toward worse outcomes in small RCTs, GLP-1 receptor agonists should be used with caution in patients with established HFrEF and recent decompensation.

Recommendations

• If GLP-1 therapy is deemed necessary, start with the lowest possible dose (e.g., semaglutide 0.25mg weekly or liraglutide 0.6mg daily) and titrate very slowly while monitoring fluid status, blood pressure, and heart rate.
• Ensure the patient maintains adequate hydration and electrolyte balance.
• Consider temporarily suspending the medication during acute illness or periods of reduced oral intake.
• While some GLP-1 agonists have shown cardiovascular benefits in certain populations, the specific combination of atrial fibrillation, volume depletion, and cardiomyopathy represents a higher-risk scenario requiring individualized assessment of benefit versus risk, as suggested by studies published in Circulation 1.

From the Research

Risks of GLP-1 in a Person with Atrial Fibrillation, Volume Depletion, and Cardiomyopathy

• The use of GLP-1 receptor agonists in patients with atrial fibrillation (AF) has been studied, and the results suggest that these agents may improve myocardial metabolism in the presence of various risk factors, potentially lowering the incidence of AF 2.
• Atrial fibrillation is a common cardiac arrhythmia that increases with age and presents with a wide spectrum of symptoms and severity, requiring individualized approaches to management 3.
• The treatment of AF mainly includes drug therapy, catheter ablation, cryoballoon ablation, left atrial appendage closure, and the maze procedure, with the goal of preventing and controlling AF 4.
• Meta-analyses have shown that GLP-1 receptor agonists are associated with a reduction in major cardiovascular events, cardiovascular and all-cause mortality, stroke, and possibly myocardial infarction, with no significant increase in the risk of atrial fibrillation 5, 6.
• However, one study suggested that albiglutide, a GLP-1 receptor agonist, may be associated with an increased risk of atrial fibrillation, although this finding was not consistent across all studies 6.
• In patients with volume depletion and cardiomyopathy, the use of GLP-1 receptor agonists may need to be carefully considered, as these conditions may affect the cardiovascular system and potentially interact with the effects of GLP-1 receptor agonists on the heart 2, 5.