Question of the Day
Wednesday, November 11, 2026
A 72-year-old man with heart failure with preserved ejection fraction (ejection fraction 58%) presents for management. He does not have diabetes mellitus. His medications are lisinopril, carvedilol, and furosemide. He is euvolemic on examination, with a blood pressure of 132/78 mm Hg, a serum potassium level of 4.3 mEq/L, and an eGFR of 60 mL/min/1.73 m2. He has exertional dyspnea and has been hospitalized twice in the past year for heart failure exacerbations. Which one of the following is the most appropriate addition to reduce his risk of heart failure hospitalization?
Answer: D. Empagliflozin
The correct answer is D (Empagliflozin). In EMPEROR-Preserved, empagliflozin reduced the composite of cardiovascular death or heart failure hospitalization by about 21% in patients with an ejection fraction above 40%, driven by fewer hospitalizations and independent of diabetes; dapagliflozin showed similar benefit in DELIVER. The 2022 AHA/ACC/HFSA guideline gives SGLT2 inhibitors the strongest recommendation of any drug class for HFpEF, and later expert consensus places them first.
Why not A (Sacubitril-valsartan in place of lisinopril): PARAGON-HF narrowly missed its primary endpoint, so ARNI therapy carries only a weak (2b) recommendation in HFpEF, with any benefit concentrated at an ejection fraction near the lower end of normal, not 58%.
Why not B (Digoxin): Digoxin has not been shown to reduce hospitalization or mortality in HFpEF and has a narrow therapeutic window in older adults.
Why not C (Ivabradine): Ivabradine reduces hospitalization only in HFrEF with sinus rhythm and a resting heart rate of 70 beats/min or more on a beta-blocker; it has no role in HFpEF.
Why not E (Metolazone): Adding a thiazide-type diuretic helps diuretic-resistant congestion, but he is euvolemic, and metolazone causes electrolyte disturbances without outcome benefit.
Clinical Pearl: For symptomatic HFpEF, add an SGLT2 inhibitor to reduce heart failure hospitalizations, with or without diabetes.
Just show me the answer
Answer: D. Empagliflozin
The correct answer is D (Empagliflozin). In EMPEROR-Preserved, empagliflozin reduced the composite of cardiovascular death or heart failure hospitalization by about 21% in patients with an ejection fraction above 40%, driven by fewer hospitalizations and independent of diabetes; dapagliflozin showed similar benefit in DELIVER. The 2022 AHA/ACC/HFSA guideline gives SGLT2 inhibitors the strongest recommendation of any drug class for HFpEF, and later expert consensus places them first.
Why not A (Sacubitril-valsartan in place of lisinopril): PARAGON-HF narrowly missed its primary endpoint, so ARNI therapy carries only a weak (2b) recommendation in HFpEF, with any benefit concentrated at an ejection fraction near the lower end of normal, not 58%.
Why not B (Digoxin): Digoxin has not been shown to reduce hospitalization or mortality in HFpEF and has a narrow therapeutic window in older adults.
Why not C (Ivabradine): Ivabradine reduces hospitalization only in HFrEF with sinus rhythm and a resting heart rate of 70 beats/min or more on a beta-blocker; it has no role in HFpEF.
Why not E (Metolazone): Adding a thiazide-type diuretic helps diuretic-resistant congestion, but he is euvolemic, and metolazone causes electrolyte disturbances without outcome benefit.
Clinical Pearl: For symptomatic HFpEF, add an SGLT2 inhibitor to reduce heart failure hospitalizations, with or without diabetes.
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