HFpEF Treatment Options

As a clinical pharmacy specialist, you will get questions about managing heart failure with PRESERVED ejection fraction (HFpEF), based on new guidance. Over half of HF patients have HFpEF, with an ejection fraction of 50% or higher. But treatment of HFpEF is still less clear-cut than heart failure with REDUCED ejection fraction (HFrEF), since HFpEF data are less robust and medications aren’t shown to reduce mortality so far.

     Continue to emphasize BP control, it may slow HFpEF progression. Optimize management of common conditions that may worsen HFpEF, such as atrial fibrillation, COPD, and obesity. And use loop diuretics if needed for fluid overload. But keep in mind, reducing preload too much can worsen HFpEF symptoms. Then consider key medications that may improve HFpEF outcomes, weighing the strength of evidence, side effects, cost, etc. Add one of SGLT2 inhibitors if practical. For example, Forxiga (dapagliflozin) or Jardiance (empagliflozin) prevents HF hospitalization in about 1 in 35 patients with HFpEF over about 2 years. New Inpefa (sotagliflozin) ã…¡ NOT available in Egypt ã…¡ is also an option, but has less data. These medications may be started with eGFR down to 20 mL/min/1.73 m². And all 3 are now approved for HF, including HFpEF, regardless of diabetes. But weigh downsides, such as genital yeast infections, volume depletion, and cost. Also consider adding spironolactone (aldosterone antagonists). Limited evidence suggests it may reduce HFpEF hospitalizations, but only after a reanalysis of data.

Table (1). Starting and Target Doses of Select GDMTs for HFpEF
Drug Class Starting Dose Target Dose
SGLT2is
Dapagliflozin 10 mg daily 10 mg daily
Empagliflozin 10 mg daily 10 mg daily
Aldosterone antagonists
Spironolactone 25 mg daily 50 mg daily
ARNIs
Sacubitril/valsartan 24 mg/26 mg twice daily 97 mg/103 mg twice daily
ARBs
Candesartan 4 mg to 8 mg daily 32 mg daily
ARB = angiotensin receptor blocker; ARNI = angiotensin receptor–neprilysin inhibitor; GDMT = guideline-directed medical therapy; HFpEF = heart failure with preserved ejection fraction; SGLT2 = sodium-glucose cotransporter-2.

ACEIs, ARBs, or Entresto (sacubitril/valsartan), some evidence suggests any of these medications might reduce HFpEF hospitalizations. But this relies on secondary endpoints or subgroups to find benefit. Think of Entresto as having stronger data than ACEIs or ARBs. But Entresto isn’t always practical. For example, it may cause low BP, even in HFpEF, and it is expensive. If Entresto isn’t an option, generally choose an ARB over an ACEI. Either is reasonable for patients with other indications (hypertension, etc), but ACEIs have the least data suggesting benefit in HFpEF. Ensure close monitoring, such as electrolytes, kidney function, and volume status, especially when adding or titrating medications. Get our notes, "Managing diastolic or preserved ejection fraction heart failure (HFpEF)" AND "Know the role of empagliflozin (JARDIANCE) in heart failure with preserved ejection fraction" for more information.

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Figure 1. Treatment Algorithm for Guideline-Directed Medical Therapy in HFpEF.

AF = atrial fibrillation; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor-neprilysin inhibitor; EF = ejection fraction; HFpEF = heart failure with preserved ejection fraction; LVEF = left ventricular ejection fraction; MRA = mineralocorticoid antagonist; NYHA = New York Heart Association; SGLT2i = sodium-glucose cotransporter 2 inhibitor.

REFERENCES

  • Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M, Lund LH, Komajda M, Testani JM, Wilcox CS, Ponikowski P, Lopes RD, Verma S, Lapuerta P, Pitt B; SOLOIST-WHF Trial Investigators. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2030183

    Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Inzucchi SE, Kosiborod MN, Cherney DZI, Dwyer JP, Scirica BM, Bailey CJ, Díaz R, Ray KK, Udell JA, Lopes RD, Lapuerta P, Steg PG; SCORED Investigators. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021 Jan 14;384(2):129-139. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2030186

    Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW. 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. Circulation. 2022 May 3;145(18):e895-e1032. Available at: https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063

    Kittleson MM, Panjrath GS, Amancherla K, Davis LL, Deswal A, Dixon DL, Januzzi JL Jr, Yancy CW. 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 May 9;81(18):1835-1878. Available at: https://www.sciencedirect.com/science/article/pii/S0735109723050982?via%3Dihub

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