How do GLP-1 (Glucagon-like peptide-1) agonists help in the management of heart failure?

GLP-1 Receptor Agonists in Heart Failure Management

GLP-1 receptor agonists should be used with caution in heart failure, with different recommendations based on ejection fraction status, as they may reduce atherosclerotic events but have uncertain or potentially harmful effects in established heart failure with reduced ejection fraction. 1, 2

Cardiovascular Effects of GLP-1 Receptor Agonists

GLP-1 receptor agonists (GLP-1 RAs) have several mechanisms that potentially benefit cardiovascular health:

• Reduction in major adverse cardiovascular events (MACE) by 13-26% in patients with type 2 diabetes and established cardiovascular disease 2
• Significant cardiovascular death reduction with liraglutide (22% reduction, HR 0.78) 2
• FDA-approved indications for reducing cardiovascular risk in adults with type 2 diabetes and established cardiovascular disease 3, 4

Differential Effects Based on Heart Failure Status

In Patients Without Heart Failure

• GLP-1 RAs reduce the risk of atherosclerotic events regardless of heart failure history (HR 0.88,95% CI: 0.83-0.93) 5
• May prevent new-onset heart failure and reduce mortality in patients with type 2 diabetes without existing heart failure 5
• Reduce the composite of heart failure hospitalization or cardiovascular death in patients without heart failure history (HR 0.84,95% CI: 0.76-0.92) 5

In Heart Failure with Preserved Ejection Fraction (HFpEF)

• May improve functional capacity as measured by 6-minute walk test distance (MD: 19.74, p=0.002) 6
• Associated with lower incidence of heart failure exacerbation events (HR 0.60) and all-cause emergency room visits or hospitalizations (HR 0.67) in non-obese patients with type 2 diabetes and HFpEF 7
• Do not reduce heart failure hospitalizations but may reduce atherosclerotic events 8

In Heart Failure with Reduced Ejection Fraction (HFrEF)

• Use warrants caution due to potential risk of worsening heart failure events and arrhythmias 8
• American Heart Association recommends using GLP-1 RAs with caution in patients with HFrEF due to potential worsening of outcomes 2
• Do not reduce the composite of heart failure hospitalization or cardiovascular death in patients with heart failure history (HR 0.96,95% CI: 0.84-1.08) 5

Current Guideline Recommendations

Multiple guidelines provide recommendations for GLP-1 RAs in heart failure:

• American Heart Association/Heart Failure Society of America (2019): GLP-1 RAs have no effect on heart failure hospitalization risk, suggesting they are safe but not beneficial in preventing heart failure in at-risk patients 1
• European Society of Cardiology Guidelines on Diabetes (2019): GLP-1 RAs may be considered in patients with type 2 diabetes and heart failure 1
• European Association for the Study of Diabetes (2019): If heart failure predominates, prefer SGLT-2 inhibitors; if SGLT-2 inhibitors are not tolerated or contraindicated, use GLP-1 RAs 1

Clinical Decision Algorithm for GLP-1 RA Use in Heart Failure

1. Screen for heart failure before initiating GLP-1 RAs:

   • Directed clinical history and physical examination
   • Echocardiogram
   • Natriuretic peptide measurement 8

2. Based on heart failure status:

   • No heart failure: GLP-1 RAs recommended for reducing risk of myocardial infarction, stroke, and possibly heart failure hospitalizations
   • HFpEF: Consider individualized use; may improve functional capacity and reduce atherosclerotic events
   • HFrEF: Use with caution due to potential risk of worsening heart failure events 8

Important Caveats and Monitoring

• Monitor for gastrointestinal side effects, which are typically dose-dependent and transient 2
• Evaluate renal function when initiating or escalating doses 2
• Regular retinal examinations are recommended, especially in patients with pre-existing diabetic retinopathy 2
• Contraindicated in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 2, 3

Conclusion

The evidence suggests that GLP-1 RAs have different effects across the heart failure spectrum. While they reduce atherosclerotic events in patients with type 2 diabetes regardless of heart failure status, their effects on heart failure outcomes vary based on ejection fraction. Careful patient selection and monitoring are essential when considering GLP-1 RAs in patients with heart failure.