From the Guidelines
Goal-directed medical therapy for heart failure differs significantly between HFpEF and HFrEF, with HFrEF having more established mortality benefits from medications such as ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as well as newer agents like sacubitril/valsartan, whereas HFpEF treatment focuses on symptom management, blood pressure control, and addressing underlying conditions, with fewer therapies having proven mortality benefits, as noted in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
Key Differences in Treatment
- For HFrEF, several medication classes have proven mortality benefits, including:
- ACE inhibitors/ARBs (like lisinopril 10-40 mg daily or valsartan 80-320 mg daily)
- Beta-blockers (carvedilol 3.125-25 mg twice daily, metoprolol succinate 25-200 mg daily, or bisoprolol 1.25-10 mg daily)
- Mineralocorticoid receptor antagonists (spironolactone 25-50 mg daily or eplerenone 25-50 mg daily)
- SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily)
- Newer agents like sacubitril/valsartan (24/26 mg to 97/103 mg twice daily) have further improved outcomes, as seen in the optimal background pharmacological therapy for heart failure patients in clinical trials 1
- In contrast, HFpEF has fewer therapies with proven mortality benefits, with treatment often focusing on:
- Symptom management
- Blood pressure control
- Addressing underlying conditions like atrial fibrillation and coronary disease
- SGLT2 inhibitors have shown reduction in heart failure hospitalizations in HFpEF, and spironolactone may benefit selected patients, as discussed in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1
Pathophysiological Differences
- HFpEF represents a more heterogeneous syndrome with multiple pathophysiological mechanisms
- HFrEF has a more uniform pathophysiology related to reduced contractility, making targeted therapies more effective in the latter, as explained in the 2020 international society of hypertension global hypertension practice guidelines 1
Clinical Implications
- The difference in treatment approaches between HFpEF and HFrEF highlights the importance of accurate diagnosis and tailored therapy to improve morbidity and mortality outcomes, as emphasized in the 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1
- Clinicians should prioritize the use of evidence-based therapies for HFrEF, while also addressing underlying conditions and symptoms in HFpEF patients, as recommended in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1
From the FDA Drug Label
1 INDICATIONS AND USAGE
1.1 Adult Heart Failure Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction.
The FDA drug label does not provide direct guidelines for Heart Failure with preserved Ejection Fraction (HFpEF). For Heart Failure with reduced Ejection Fraction (HFrEF), the goal-directed medical therapy is to reduce the risk of cardiovascular death and hospitalization for heart failure.
- The recommended treatment for HFrEF is sacubitril and valsartan tablets, which have been shown to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction 2.
- Valsartan has also been studied in the treatment of heart failure, and has been shown to reduce the risk of heart failure morbidity in patients not receiving an ACE inhibitor 3.
However, there is no direct information in the provided drug labels regarding the treatment of HFpEF.
From the Research
Goal-Directed Medical Therapy Guidelines for HFpEF and HFrEF
The goal-directed medical therapy guidelines for Heart Failure with preserved Ejection Fraction (HFpEF) and Heart Failure with reduced Ejection Fraction (HFrEF) differ in terms of morbidity and mortality.
- For HFpEF, the current therapeutic approaches are targeted towards alleviating the symptoms, treating the associated comorbid conditions, and reducing recurrent hospital admissions 4.
- There is a lack of evidence-based therapies that show a reduction in mortality amongst HFpEF patients; however, an improvement in exercise tolerance and quality of life is seen with few interventions 4.
- Control of blood pressure is widely regarded as central to the prevention and clinical care in HFpEF, with blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers providing the backbone of BP-lowering therapy in hypertensive patients 5.
- Sacubitril/valsartan may provide superior benefits in reducing heart failure hospitalization rates, NT-proBNP levels, and improving NYHA classification in patients with HFpEF compared to ACEIs and ARBs 6.
Comparison of HFpEF and HFrEF
- HFpEF is a heterogeneous syndrome likely borne from the interplay of genetic predisposition, lifestyle factors, and high burden of associated comorbidities, whereas HFrEF is characterized by a reduced ejection fraction 7.
- The proportion of HF patients with HFpEF varies by patient demographics, study settings, and cut points used to define preserved function, whereas HFrEF is typically defined by a reduced ejection fraction 4.
- The diagnosis of HFpEF relies on the integration of clinical information, laboratory data, and interpretation of cardiac imaging and hemodynamic findings at rest and during exercise, whereas HFrEF is typically diagnosed based on echocardiography 8.
Morbidity and Mortality
- HFpEF is associated with increased cardiovascular morbidity and mortality, with a lack of evidence-based therapies that show a reduction in mortality amongst HFpEF patients 5.
- Sacubitril/valsartan did not affect total mortality from all causes significantly, but it did enhance NYHA classification and reduce heart failure hospitalization rates in patients with HFpEF 6.
- The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action 5.