In a man over 65 years old with heart failure with preserved ejection fraction, mild concentric left ventricular hypertrophy, low stroke‑volume index, hypertension, type 2 diabetes, hyperlipidemia, chronic kidney disease, coronary artery disease, and currently on eplerenone 25 mg daily, is continuing eplerenone appropriate or should an SGLT2 inhibitor (dapagliflozin or empagliflozin) be started now before his cardiovascular specialty appointment?

SGLT2 Inhibitor Should Be Started Now

In this patient with HFpEF, type 2 diabetes, and multiple comorbidities, an SGLT2 inhibitor (empagliflozin 10 mg or dapagliflozin 10 mg daily) should be initiated immediately rather than waiting for the cardiovascular specialty appointment, while continuing the eplerenone 25 mg. Both medications address different therapeutic targets and should be used together as complementary guideline-directed medical therapy.

Rationale for Adding SGLT2 Inhibitor Now

SGLT2 inhibitors are Class 2a recommended therapy for HFpEF and represent the first pharmacological class proven to reduce HF hospitalizations and cardiovascular mortality in patients with preserved ejection fraction 1. The 2022 AHA/ACC/HFSA guidelines specifically recommend SGLT2 inhibitors for symptomatic HFpEF patients with LVEF ≥40% and elevated natriuretic peptides 1.

Evidence Supporting Immediate Initiation

• Empagliflozin reduced the composite endpoint of HF hospitalization or cardiovascular death by 21% (HR 0.79; 95% CI 0.69-0.90) in EMPEROR-Preserved, driven primarily by a 29% reduction in HF hospitalizations 1, 2
• The benefit occurs regardless of diabetes status, making this patient with type 2 diabetes an ideal candidate 3
• Dapagliflozin demonstrated a 27% reduction in the composite outcome of HF hospitalization plus cardiovascular mortality in DELIVER 4
• Benefits extend across the entire LVEF spectrum in HFpEF, though effects may be slightly greater at lower EF ranges (closer to 50% vs >60%) 1, 2

Why Eplerenone Should Be Continued

The eplerenone 25 mg should be maintained because mineralocorticoid receptor antagonists (MRAs) and SGLT2 inhibitors work through different mechanisms and can be safely combined 1.

Complementary Mechanisms

• SGLT2 inhibitors reduce hyperkalemia risk when used with RAAS inhibitors and MRAs (hazard ratio 0.84; 95% CI 0.76-0.93), actually facilitating continuation of MRA therapy 1
• MRAs address neurohormonal activation while SGLT2 inhibitors provide hemodynamic benefits, improved cardiac metabolism, and anti-inflammatory effects 5
• The combination allows optimization of guideline-directed medical therapy without requiring withdrawal of either agent 1

Specific Dosing Recommendations

Start empagliflozin 10 mg once daily OR dapagliflozin 10 mg once daily 2. Both have equivalent Class I evidence in HFpEF.

Drug Selection Considerations

• Empagliflozin 10 mg daily is supported by EMPEROR-Preserved data showing consistent benefit across diabetes status 3
• Dapagliflozin 10 mg daily is supported by DELIVER trial data and may have more consistent effects across the full LVEF spectrum including >60% 4
• Either agent is appropriate; choice can be based on formulary availability, cost, or patient preference 1

Safety Monitoring Requirements

Check baseline eGFR before initiation - SGLT2 inhibitors are contraindicated if eGFR <20 mL/min/1.73 m² 2. This patient with CKD requires particular attention.

Key Monitoring Parameters

• Assess volume status as SGLT2 inhibitors cause osmotic diuresis; may need to adjust loop diuretic dose 1
• Monitor potassium levels within 1-2 weeks, as the combination of MRA and SGLT2 inhibitor typically reduces hyperkalemia risk but requires verification 1
• Check renal function at 2-4 weeks, expecting initial small decline in eGFR (hemodynamic effect) followed by long-term preservation 1
• Educate on genital mycotic infection risk and diabetic ketoacidosis warning signs (though risk is low in type 2 diabetes) 2

Why Not Wait for Specialty Appointment

Delaying SGLT2 inhibitor initiation means missing immediate therapeutic benefit in a patient at high risk for HF hospitalization 1.

Time-Sensitive Considerations

• Benefits begin within weeks - DELIVER showed separation of event curves within the first month 4
• The patient has multiple high-risk features: diabetes, CKD, CAD, hypertension, and low stroke volume index 1
• SGLT2 inhibitors are safe to initiate in primary care with appropriate monitoring and do not require specialty oversight for initiation 1
• The cardiovascular specialist will likely recommend this anyway, so starting now provides earlier protection 1, 2

Addressing the Low Eplerenone Dose

The eplerenone 25 mg daily is a reasonable starting dose but may be suboptimal long-term. However, this should be addressed separately from the SGLT2 inhibitor decision.

MRA Optimization Strategy

• Target eplerenone dose is typically 50 mg daily for HF, but 25 mg may be appropriate given CKD and need to avoid hyperkalemia 1
• Adding SGLT2 inhibitor may actually facilitate MRA uptitration by reducing hyperkalemia risk 1
• Reassess MRA dosing at 2-4 weeks after SGLT2 inhibitor initiation when potassium levels are rechecked 1

Common Pitfalls to Avoid

• Do not discontinue eplerenone to start SGLT2 inhibitor - they are complementary, not alternatives 1, 6
• Do not wait for "perfect" volume status - SGLT2 inhibitors can be initiated in euvolemic or mildly congested patients 1
• Do not withhold due to CKD unless eGFR <20 mL/min/1.73 m² - renal protection is actually a benefit 1
• Do not reduce SGLT2 inhibitor dose below recommended 10 mg unless specific contraindications exist 2