What medication should be started for a patient with heart failure with preserved ejection fraction (HFpEF), type 2 diabetes mellitus, hypertension, and obesity, who is currently asymptomatic and euvolemic after diuresis?

Recommendation for Hospital Discharge Medication

You should recommend starting canagliflozin (Option B) for this patient with HFpEF, type 2 diabetes mellitus, hypertension, and obesity who is now euvolemic and asymptomatic after diuresis.

Rationale Based on Guideline-Directed Medical Therapy

SGLT2 Inhibitors as Class I Recommendation for HFpEF

• SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are recommended in patients with T2DM and CVD, or at very high/high CV risk, to reduce CV events 1
• SGLT2 inhibitors are specifically recommended to lower risk of HF hospitalization in patients with diabetes 1
• The 2024 ESC guidelines provide a Class I, Level A recommendation for SGLT2 inhibitors (dapagliflozin or empagliflozin) in patients with HFpEF to reduce the risk of HF hospitalization or cardiovascular death 1

Why Canagliflozin is the Optimal Choice

• This patient has multiple indications for SGLT2 inhibitor therapy: HFpEF with recent decompensation, type 2 diabetes mellitus, obesity, and established cardiovascular disease (atrial fibrillation) 1
• Canagliflozin has demonstrated cardiovascular benefits in the CANVAS program, reducing the composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke (HR 0.86,95% CI 0.75-0.97) 2
• In the CREDENCE trial, canagliflozin 100 mg significantly reduced hospitalization for heart failure (HR 0.61,95% CI 0.47-0.80, p<0.001) in patients with diabetic nephropathy 2

Timing of Initiation

• ACC/AHA HF guidelines have an explicit Class I recommendation for in-hospital or before hospital discharge initiation of guideline-directed medical therapy if not previously established, in absence of contraindications 1
• The patient is now euvolemic and asymptomatic, making this the ideal time to initiate SGLT2 inhibitor therapy before discharge 1

Why Other Options Are Not Preferred

Amiodarone (Option A) - Not Indicated

• Amiodarone is not recommended for this patient because adequate rate control of atrial fibrillation was already achieved by restarting metoprolol succinate 1
• The patient is asymptomatic with controlled atrial fibrillation, so rhythm control with amiodarone is not necessary and would expose the patient to unnecessary toxicity risks 1

Isosorbide Dinitrate and Hydralazine (Option C) - Wrong Population

• This combination is not indicated for HFpEF patients 1
• Isosorbide dinitrate and hydralazine have evidence primarily in HFrEF, particularly in African American patients, not in HFpEF 1
• The patient has preserved ejection fraction, making this combination inappropriate 1

Practical Implementation Algorithm

Starting Canagliflozin

• Initiate canagliflozin 100 mg once daily, which can be uptitrated to 300 mg once daily if needed for glycemic control 2
• The 100 mg dose has demonstrated significant cardiovascular and heart failure benefits 2

Monitoring Parameters

• Monitor renal function before initiation and periodically thereafter, as SGLT2 inhibitors are contraindicated with eGFR <30 mL/min/1.73 m² 1
• Assess volume status regularly due to the osmotic diuretic effect of SGLT2 inhibitors 3, 4
• Monitor for genital and urinary tract infections, which are the most common adverse events consistent with the mechanism of action 5

Additional Considerations for This Patient

Comprehensive Diabetes Management

• The patient is already on metformin and glipizide, which should be continued 1
• Consider discontinuing glipizide if adequate glycemic control is achieved with metformin and canagliflozin, as sulfonylureas should only be used if unable to achieve adequate control with alternative options 1

Common Pitfalls to Avoid

• Do not withhold SGLT2 inhibitor therapy simply because the patient has HFpEF rather than HFrEF - the evidence now supports use in both populations 1, 3
• Do not delay initiation until outpatient follow-up - in-hospital initiation before discharge is recommended and improves adherence 1
• Be aware of the increased amputation and fracture risk observed with canagliflozin in some studies, though these require further investigation 5

Expected Benefits

• Reduction in HF hospitalizations, which is particularly important given this patient's recent acute decompensation 1, 2
• Cardiovascular mortality reduction 1, 2
• Weight loss of 2-4 kg, beneficial for this obese patient 4
• Blood pressure reduction through osmotic diuresis and natriuresis 4
• Improved glycemic control with low hypoglycemia risk 6, 5