Can a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor and an Angiotensin-Converting Enzyme (ACE) inhibitor be added to the treatment regimen of a patient with Heart Failure with Preserved Ejection Fraction (HFpEF) and impaired renal function, with an estimated Glomerular Filtration Rate (eGFR) of 38?

SGLT2 Inhibitor and ACE Inhibitor in HFpEF with eGFR 38

Yes, both an SGLT2 inhibitor and an ACE inhibitor can and should be added to this patient's regimen, with the SGLT2 inhibitor being particularly important as it represents guideline-directed medical therapy for HFpEF regardless of the eGFR of 38 mL/min/1.73 m².

SGLT2 Inhibitor Recommendation

An SGLT2 inhibitor (empagliflozin or dapagliflozin) is strongly recommended for this patient with HFpEF, as it reduces heart failure hospitalizations and cardiovascular mortality. 1

Specific Agent Selection Based on eGFR 38:

• Empagliflozin is the preferred choice at this eGFR level, as it can be initiated down to eGFR ≥20 mL/min/1.73 m² 1, 2
• Dapagliflozin can also be used, though it is approved down to eGFR ≥25 mL/min/1.73 m² for heart failure 1
• Empagliflozin should NOT be initiated if eGFR is <20 mL/min/1.73 m², but can be continued if eGFR falls below this threshold after initiation 2

Evidence Supporting SGLT2 Inhibitors in HFpEF:

• The 2024 ESC guidelines give a Class I, Level A recommendation for SGLT2 inhibitors (dapagliflozin or empagliflozin) in HFpEF to reduce heart failure hospitalization and cardiovascular death 1
• The 2024 ACC/AHA quality measures specifically recommend SGLT2 inhibitors for patients with LVEF >40% (Class 2a, Level B-R) 1
• SGLT2 inhibitors reduce cardiovascular hospitalization by 21-29% in HFpEF patients 3, 4
• These benefits occur regardless of diabetes status, baseline eGFR, blood pressure, or other comorbidities 4, 5

Key Advantages at This eGFR:

• SGLT2 inhibitors do not affect blood pressure, heart rate, or potassium levels, making them easier to initiate 1
• They require no dose titration—start at target dose 1
• They provide long-term kidney protection despite a mild, transient drop in eGFR after initiation 1
• Benefits occur within weeks of initiation 1

ACE Inhibitor Recommendation

An ACE inhibitor can be added for this patient, though the primary indication in HFpEF is less robust than in HFrEF.

Considerations for ACE Inhibitor Use:

• The 2024 ESC guidelines recommend ACE inhibitors primarily for patients with HFrEF (Class I, Level A), not specifically for HFpEF 1
• However, ACE inhibitors are recommended for chronic coronary syndrome patients with heart failure 1
• If this patient has hypertension, diabetes with proteinuria, or coronary artery disease, an ACE inhibitor provides additional cardiovascular and renal protection 1

Dosing with eGFR 38:

• ACE inhibitors can be safely used at eGFR 38 mL/min/1.73 m² 6
• Monitor renal function and potassium closely after initiation, as eGFR may transiently decrease 6
• Dose adjustment is generally not required until eGFR falls below 30 mL/min/1.73 m² 6

Implementation Strategy

Initiation Sequence:

1. Start with the SGLT2 inhibitor first (empagliflozin 10 mg daily), as it has the strongest evidence in HFpEF and does not affect blood pressure or electrolytes 1, 2
2. After 1-2 weeks, assess tolerance and check renal function 1
3. Then add the ACE inhibitor if indicated for comorbid conditions (hypertension, CAD, diabetes with proteinuria) 1
4. Start ACE inhibitor at low dose and titrate gradually while monitoring blood pressure, renal function, and potassium 6

Monitoring Parameters:

• Check eGFR and potassium within 1-2 weeks after initiating each medication 1, 6
• Expect a mild, transient decrease in eGFR (5-10%) with SGLT2 inhibitor—this is not a reason to discontinue 1
• Monitor for hyperkalemia, especially if adding an ACE inhibitor to other RAAS blockers 1
• Assess blood pressure if adding ACE inhibitor, though SGLT2 inhibitor alone should not cause hypotension 1

Important Caveats

SGLT2 Inhibitor Contraindications/Cautions:

• Temporarily discontinue before scheduled surgery (3-4 days) to reduce diabetic ketoacidosis risk 1
• Educate on genital hygiene to prevent mycotic infections 1
• Ensure adequate hydration, especially during illness or with concurrent diuretic use 1
• Monitor for rare but serious Fournier's gangrene 1

ACE Inhibitor Contraindications:

• Do not combine ACE inhibitor with ARB and MRA (triple RAAS blockade) due to hyperkalemia and renal dysfunction risk 1
• Avoid in pregnancy 6
• Monitor for angioedema 6

Common Pitfall to Avoid:

Do not withhold SGLT2 inhibitors due to the eGFR of 38—this is well above the threshold for initiation and the patient will derive significant benefit. The glucose-lowering effect diminishes below eGFR 45, but the cardiovascular and renal protective effects persist down to eGFR 20-25 mL/min/1.73 m² 1, 2