What medication reduces mortality in Heart Failure with preserved Ejection Fraction (HFpEF)?

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Last updated: March 24, 2025View editorial policy

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From the Guidelines

Sacubitril-valsartan is the only medication that has shown a potential reduction in mortality in a specific subgroup of patients with Heart Failure with preserved Ejection Fraction (HFpEF), particularly in women, as evidenced by the PARAGON-HF trial 1.

Medication Overview

The management of HFpEF is primarily focused on symptom relief and the aggressive treatment of risk factors and cardiovascular/noncardiovascular comorbidities according to clinical guidelines 1.

  • Sacubitril-valsartan has been studied in the PARAGON-HF trial, which compared it to valsartan in patients with HFpEF, elevated baseline levels of natriuretic peptides, and structural heart disease 1.
  • The trial found that sacubitril-valsartan did not reduce the primary composite outcome of total HFH and cardiovascular death compared to valsartan, but a prespecified subgroup analysis showed a potential benefit in women, with a relative risk of 0.73 for the primary outcome 1.

Clinical Considerations

  • The use of sacubitril-valsartan in HFpEF patients, particularly women, may be considered based on the results of the PARAGON-HF trial, but more research is needed to confirm these findings 1.
  • Other medications, such as beta-blockers and ARBs, may provide symptomatic benefit in HFpEF but have not conclusively shown mortality reduction 1.
  • The choice of antihypertensive therapy in HFpEF should be guided by a shared decision-making discussion with the patient, influenced by clinician judgment, and consideration of the patient's individual characteristics and comorbidities 1.

Monitoring and Side Effects

  • When initiating sacubitril-valsartan, patients should be monitored for potential side effects, including hypotension, renal dysfunction, and hyperkalemia 1.
  • Dose adjustments may be necessary based on the patient's renal function and blood pressure response 1.

From the Research

Medication for Heart Failure with Preserved Ejection Fraction (HFpEF)

  • There is evidence to suggest that beta-blockers may reduce mortality in HFpEF, with a meta-analysis of observational cohort and randomized controlled studies showing a 21% reduction in risk of mortality [ 2 ].
  • SGLT2 inhibitors, such as empagliflozin, have also shown promise in reducing hospitalization for heart failure in HFpEF patients, although their effect on cardiovascular mortality is unclear [ 3 ].
  • Other studies have highlighted the complexity and heterogeneity of HFpEF, suggesting that therapeutic strategies may need to be tailored to individual patient phenotypes [ 4, 5 ].
  • However, it is worth noting that some studies have focused on heart failure with reduced ejection fraction (HFrEF) rather than HFpEF, and may not be directly applicable to HFpEF patients [ 6 ].

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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