Do GLP-1 (Glucagon-like peptide-1) receptor agonists have cardiovascular benefits in patients with a history of myocardial infarction (MI) and depressed ejection fraction (EF)?

GLP-1 Receptor Agonists Have Cardiovascular Benefits After MI in Patients with Depressed EF

GLP-1 receptor agonists are recommended for patients with a history of MI and depressed ejection fraction to reduce cardiovascular events, particularly in those with type 2 diabetes. 1

Cardiovascular Benefits in Post-MI Patients with Depressed EF

Evidence for Cardiovascular Protection

• GLP-1 receptor agonists provide cardioprotective effects through multiple mechanisms:

  • Improved myocardial substrate utilization
  • Anti-inflammatory and anti-atherosclerotic effects
  • Reduced myocardial ischemia injury
  • Lower systemic and pulmonary vascular resistance
  • Improved lipid profiles 1

• Major cardiovascular outcome trials have demonstrated significant benefits:

  • The LEADER trial showed liraglutide reduced the primary composite outcome of cardiovascular death, non-fatal MI, or stroke by 13% compared to placebo (HR 0.87,95% CI 0.78-0.97) 1, 2
  • SUSTAIN-6 demonstrated semaglutide reduced the primary outcome of cardiovascular death, non-fatal MI, or stroke by 26% compared to placebo (HR 0.74,95% CI 0.58-0.95) 1

Benefits in Patients with Depressed EF

• In patients with cardiac surgery, liraglutide was associated with improved left ventricular systolic function postoperatively (68% vs 53% with normal function, p=0.049) 1
• GLP-1 receptor agonists can improve systolic function measured by circumferential strain and diastolic function measured by E/A ratio in patients with type 2 diabetes 3
• Liraglutide specifically has shown improved systolic function by increasing left ventricular ejection fraction and reducing left ventricular end-systolic volume 3

Clinical Recommendations Based on Patient Profile

For Patients with Type 2 Diabetes

• The 2024 ESC Guidelines for Chronic Coronary Syndromes strongly recommend GLP-1 receptor agonists with proven CV benefit in patients with type 2 diabetes and coronary syndromes (including post-MI) to reduce cardiovascular events (Class I, Level A recommendation) 1
• These benefits are independent of baseline HbA1c or concomitant glucose-lowering medication 1

For Non-Diabetic Patients

• The GLP-1 receptor agonist semaglutide should be considered in overweight (BMI >27 kg/m²) or obese patients with chronic coronary syndrome without diabetes to reduce CV mortality, MI, or stroke (Class IIa, Level B recommendation) 1
• A recent randomized double-blind study showed semaglutide 2.4 mg weekly reduced the primary cardiovascular endpoint in non-diabetic patients with pre-existing cardiovascular disease and BMI >27 (6.5% vs 8.2%, p=0.001) 1

Important Considerations and Cautions

Heart Failure Considerations

• Caution is warranted in patients with established heart failure with reduced ejection fraction (HFrEF) 4, 5
• GLP-1 receptor agonists did not reduce the composite of HF hospitalization or cardiovascular death in patients with a history of HF (HR 0.96,95% CI: 0.84-1.08) 6
• For patients with HFrEF, SGLT2 inhibitors may be a preferred option 1, 4

Monitoring and Management

• Common adverse effects include:
  • Gastrointestinal effects (nausea, vomiting, diarrhea)
  • Potential for cardiac arrhythmia/tachycardia 1
• Start GLP-1 receptor agonist at a low dose and titrate upward slowly to minimize side effects 1
• If cardiac symptoms occur, monitor and consider beta blockers for tachycardia 1

Specific Agent Selection

• Liraglutide has FDA approval specifically for reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease 2
• Semaglutide is also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease 7
• For patients with both diabetes and depressed EF post-MI, the evidence is strongest for liraglutide and semaglutide 1

In conclusion, GLP-1 receptor agonists provide significant cardiovascular benefits in patients with a history of MI and depressed EF, particularly those with type 2 diabetes. However, careful monitoring is needed in patients with established HFrEF, where SGLT2 inhibitors may be a preferred option.