What is the role of Sodium-Glucose Linked Transporter (SGLT) inhibitors, such as empagliflozin (Jardiance) or canagliflozin (Invokana), in patients with acute myocardial infarction (MI) and diabetes?

SGLT2 Inhibitors in Acute Myocardial Infarction with Diabetes

SGLT2 inhibitors should be initiated in patients with acute myocardial infarction and type 2 diabetes when clinically stable before discharge to reduce the risk of cardiovascular death, heart failure hospitalizations, and improve survival. 1, 2, 3

Mechanism of Action and Benefits

SGLT2 inhibitors work by:

• Inhibiting sodium-glucose cotransporter 2 in proximal renal tubules
• Reducing reabsorption of filtered glucose
• Increasing urinary glucose excretion
• Restoring tubuloglomerular feedback and reducing intraglomerular pressure 1, 2

The cardiovascular benefits of SGLT2 inhibitors in acute MI patients with diabetes include:

• Mortality reduction: Early use of SGLT2 inhibitors after acute MI in patients with diabetes is associated with a 32% reduction in all-cause mortality (adjusted HR 0.68; 95% CI 0.54-0.87) 3
• Heart failure prevention: Significantly lower risk of hospitalizations for heart failure 3
• Metabolic improvements: Modification of cardiac energy metabolism and increased myocardial ATP production 4, 5
• Antioxidant effects: Increased myocardial levels of antioxidant proteins (Sirt3 and superoxide dismutase 2) 4
• Renoprotection: Prevention of acute kidney injury that often complicates MI in diabetic patients 6, 7

Patient Selection

SGLT2 inhibitors are recommended for:

• Patients with type 2 diabetes and established cardiovascular disease, including recent MI 1, 2
• Patients with heart failure (regardless of ejection fraction) 1, 2
• Patients with chronic kidney disease (eGFR ≥45 mL/min/1.73 m²) 1, 2

Specific SGLT2 Inhibitor Options

1. Empagliflozin (Jardiance):

   • FDA-approved to reduce cardiovascular death in adults with type 2 diabetes and established cardiovascular disease 8
   • Demonstrated 38% reduction in cardiovascular death (HR 0.62; 95% CI 0.49-0.77) 2
   • Dosage: 10 mg PO daily 1

2. Dapagliflozin:

   • Reduces risk of CV death and hospitalization for heart failure in adults with HFrEF 1
   • Dosage: 10 mg PO daily 1

3. Canagliflozin:

   • Reduces risk of MI, stroke, or CV death in adults with T2D and CV disease 1
   • Dosage: 100 mg PO daily 1

Timing of Initiation

• Initiate SGLT2 inhibitors when patients are clinically stable before discharge from the hospital 2
• In-hospital initiation improves post-discharge medication adherence and reduces early post-discharge events 2
• Failure to initiate during hospitalization results in >75% chance of therapy never being started within the next year 2

Contraindications and Precautions

Contraindications:

• History of serious hypersensitivity to the drug
• Pregnancy or breastfeeding
• Severe renal impairment (eGFR <30 mL/min/1.73 m²) for dapagliflozin
• End-stage renal disease or dialysis 1

Precautions:

• Discontinue at least 3 days before planned surgery (including CABG) to prevent postoperative ketoacidosis 1
• Use with caution in patients with prior amputation, severe peripheral neuropathy, or peripheral vascular disease 1
• Consider reducing diuretic dose if patient is on diuretic therapy to prevent volume depletion 1

Monitoring

• Renal function
• Signs of genital mycotic infections
• Volume status
• Symptoms of diabetic ketoacidosis (even with normal blood glucose levels)
• Lower limb ulcerations 1, 2

Potential Adverse Effects

• Genital fungal infections
• Urinary tract infections
• Euglycemic diabetic ketoacidosis
• Volume depletion
• Lower limb amputations (primarily with canagliflozin) 1, 2

Clinical Implementation Algorithm

1. Identify eligible patients: Type 2 diabetes with acute MI
2. Assess renal function: Ensure eGFR ≥30 mL/min/1.73 m²
3. Rule out contraindications: Check for hypersensitivity, pregnancy
4. Initiate therapy: Start empagliflozin 10 mg daily when clinically stable before discharge
5. Adjust concomitant medications: Consider reducing diuretic dose if applicable
6. Patient education: Explain benefits, potential side effects, and importance of adherence
7. Schedule follow-up: Within 1-2 weeks post-discharge to assess tolerance and adherence

By implementing SGLT2 inhibitors early after acute MI in patients with diabetes, clinicians can significantly improve cardiovascular outcomes and survival while providing renoprotection during this high-risk period.