Immediate Initiation of SGLT2‑Inhibitors in Patients with HFpEF

Guideline Recommendation

The 2022 AHA/ACC/HFSA guideline gives a Class 2a recommendation for adding an SGLT2‑inhibitor to guideline‑directed medical therapy in symptomatic HFpEF patients with LVEF ≥ 40 % and elevated natriuretic peptides. 1

In the EMPEROR‑Preserved trial, empagliflozin reduced the composite of HF hospitalization or cardiovascular death by 21 % (HR 0.79; 95 % CI 0.69‑0.90), driven mainly by a 29 % reduction in HF hospitalizations. This benefit was observed across the entire HFpEF population. 1
The therapeutic effect of SGLT2‑inhibitors is consistent across the full LVEF spectrum in HFpEF, with slightly larger absolute reductions when LVEF is nearer 50 % compared with >60 %. 1

MRAs (e.g., eplerenone) and SGLT2‑inhibitors act via distinct mechanisms and can be safely co‑prescribed in HFpEF. 2
When combined with RAAS inhibitors or MRAs, SGLT2‑inhibitors lower the risk of hyperkalaemia (HR 0.84; 95 % CI 0.76‑0.93), facilitating continued MRA therapy. 2
The combination allows optimization of GDMT without needing to discontinue either agent. 2

Either empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily is appropriate for HFpEF; the choice may be based on formulary availability, cost, or patient preference. Both agents have Class I evidence for benefit in this setting. [3][1]

Volume status should be assessed at initiation; dose adjustments of loop diuretics may be required because SGLT2‑inhibitors cause osmotic diuresis. 2
Serum potassium should be checked 1–2 weeks after starting therapy; the combination typically reduces hyperkalaemia risk but verification is essential. 2
Renal function (eGFR) should be re‑checked at 2–4 weeks; a modest early decline is expected, followed by long‑term preservation of kidney function. 1

Deferring SGLT2‑inhibitor initiation deprives high‑risk patients of immediate therapeutic benefit, increasing the likelihood of HF hospitalization. 1
Patients with multiple risk factors—type 2 diabetes, chronic kidney disease, coronary artery disease, hypertension, and low stroke‑volume index—derive particular urgency for early treatment. 1
Initiation can safely occur in primary‑care settings with appropriate monitoring; specialist referral is not required before starting the agent. 3

The usual target dose of eplerenone for HF is 50 mg daily, but a 25 mg dose may be reasonable in CKD to mitigate hyperkalaemia risk. 2
Adding an SGLT2‑inhibitor may facilitate uptitration of the MRA by reducing hyperkalaemia incidence. 2
Re‑assessment of MRA dosing should occur 2–4 weeks after SGLT2‑inhibitor initiation, when potassium levels have been re‑checked. 2

Do not discontinue eplerenone when starting an SGLT2‑inhibitor; the drugs are complementary. 2
Do not wait for a perfectly euvolemic state; initiation is acceptable in euvolemic or mildly congested patients. 3
Do not withhold therapy because of CKD unless eGFR is < 20 mL/min/1.73 m²; SGLT2‑inhibitors provide renal protection. [2][1]

The American Heart Association, American College of Cardiology, and Heart Failure Society of America recommend SGLT2 inhibitors as a class for HFpEF (LVEF ≥50%) with a Class 2a recommendation, stating they "can be beneficial in decreasing HF hospitalizations and cardiovascular mortality" 4, 5
The American College of Cardiology Expert Consensus specifically identifies dapagliflozin and empagliflozin as the SGLT2 inhibitors with demonstrated benefit in HFpEF, with recommended dosing of dapagliflozin 10 mg once daily or empagliflozin 10 mg once daily 6

The EMPEROR-Preserved trial demonstrated a 21% reduction in the composite endpoint of HF hospitalization or cardiovascular death (HR 0.79; 95% CI 0.69-0.90) with empagliflozin, driven primarily by a 29% reduction in HF hospitalizations 4
The American College of Cardiology recommends initiating empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily as guideline-directed medical therapy for patients with HFpEF (LVEF ≥50%), symptomatic heart failure, and elevated natriuretic peptides 6, 7

The benefit of SGLT2 inhibitors in HFpEF appears greater in patients with LVEF on the lower end of the spectrum (closer to 50% rather than >60%) 4, 5
Contraindications for SGLT2 inhibitors include eGFR <20 mL/min/1.73 m² and type 1 diabetes due to diabetic ketoacidosis risk 6, 7