Dapagliflozin would be the best next step. The results of two randomized controlled trials—DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) and EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients with chrOnic heaRt Failure)—have demonstrated the benefit of the sodium-glucose cotransporter-2 inhibitors (SGLT2is) dapagliflozin and empagliflozin in the reduction of the composite endpoint of cardiovascular (CV) death and heart failure hospitalizations (HFH). SGLT2is have a Class 2a indication for treating HFpEF in the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) Guideline for the Management of Heart Failure (HF).

In the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction) trial, sacubitril/valsartan did not reduce a composite of a reduction in CV death and HFH, nor a secondary endpoint of HFH. Subgroup analyses indicated potential benefit in women or those with EF ≤57%, which this patient does not have. Additionally, as her BP is controlled, there is no indication to switch valsartan to sacubitril/valsartan. Sacubitril/valsartan has a Class 2b indication in the 2022 AHA/ACC/HFSA guideline on HF.

In the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, the steroidal mineralocorticoid antagonist (MRA) spironolactone did not meet its composite primary endpoint of a reduction in CV death and HFH, although it did meet its secondary endpoint of a reduction in HFH and a geographical subgroup analysis confirmed benefit. In the FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure), the nonsteroidal MRA met its primary endpoint, although it is not clear whether this is a class effect. Because MRAs have a Class 2b indication in the 2022 AHA/ACC/HFSA guideline on HF, spironolactone would not be the best next step.

In the SUMMIT (A Study of Tirzepatide [LY3298176] in Participants With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity), tirzepatide reduced the composite of CV death and worsening HF in patients with HFpEF and BMI ≥30.0, although event rates were low and tirzepatide is not approved solely for a HFpEF indication. In the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity) trial, semaglutide reduced the incidence of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke in patients with prior CAD and BMI ≥27.0. However, she does not have BMI ≥27.0 and therefore would not be a candidate for incretin-based therapies.

This patient case quiz is part of the larger Managing HF Across the Spectrum: From Recognizing Symptoms to Implementing Appropriate Treatment initiative, supported by Bayer. To visit the Managing HF Across the Spectrum page and access additional educational activities on this topic, click here.

References

1. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038
2. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089-1098. doi:10.1056/NEJMoa2206286
3. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381(17):1609-1620. doi:10.1056/NEJMoa1908655
4. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392. doi:10.1056/NEJMoa1313731
5. Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2015;131(1):34-42. doi:10.1161/CIRCULATIONAHA.114.013255
6. Solomon SD, McMurray JJV, Vaduganathan M, et al. Finerenone in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2024;391(16):1475-1485. doi:10.1056/NEJMoa2407107
7. Packer M, Zile MR, Kramer CM, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med. 2025;392(5):427-437. doi:10.1056/NEJMoa2410027
8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
9. Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2023;81:1835-78.
10. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2023 Apr 18;81(15):1551. doi: 10.1016/j.jacc.2023.03.002.]. J Am Coll Cardiol. 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012