What is goal-directed medical therapy for Heart Failure with Preserved Ejection Fraction (HFpEF)?

From the Guidelines

Goal-directed medical therapy for Heart Failure with Preserved Ejection Fraction (HFpEF) should prioritize the use of SGLT2 inhibitors, such as empagliflozin or dapagliflozin, to reduce heart failure hospitalizations and improve symptoms, as evidenced by the recent EMPEROR PRESERVED and DELIVER trials 1.

Key Components of Therapy

• Diuretics like furosemide (20-80 mg daily) or hydrochlorothiazide (12.5-50 mg daily) to manage fluid overload and relieve symptoms such as dyspnea and edema.
• Blood pressure control with a target below 130/80 mmHg, using medications like ACE inhibitors, ARBs, or calcium channel blockers.
• Mineralocorticoid receptor antagonists like spironolactone (25-50 mg daily) may help certain patients, particularly those with elevated natriuretic peptide levels.
• Rate control for patients with atrial fibrillation, using beta-blockers or calcium channel blockers to maintain a resting heart rate of 60-80 beats per minute.

Lifestyle Modifications

• Sodium restriction (<2-3 g/day)
• Regular physical activity
• Weight management

Rationale

The choice of therapy is guided by the most recent and highest quality evidence, which supports the use of SGLT2 inhibitors in HFpEF patients, as shown in the EMPEROR PRESERVED and DELIVER trials 1. These trials demonstrated a reduction in the combined risk of HF hospitalizations or cardiovascular death with empagliflozin and dapagliflozin treatment. While other medications and lifestyle modifications are important, the use of SGLT2 inhibitors is a key component of goal-directed medical therapy for HFpEF. The 2022 AHA/ACC/HFSA guideline for the management of heart failure also supports the use of SGLT2 inhibitors in HFpEF patients, with a Class of Recommendation 2a 1.

From the FDA Drug Label

The efficacy of sacubitril and valsartan was evaluated in a multinational, randomized, double-blind trial PARAGON-HF comparing sacubitril and valsartan (n = 2,407) and valsartan (n = 2,389) in adult patients with heart failure with preserved ejection fraction (HFpEF).

PARAGON-HF demonstrated that sacubitril and valsartan tablets had a numerical reduction in the rate of the composite endpoint of total (first and recurrent) HF hospitalizations and CV death, based on an analysis using a proportional rates model (rate ratio [RR] 0.87; 95% CI [0.75,1.01], p = 0.06);

The treatment effect was primarily driven by the reduction in total HF hospitalizations in patients randomized to sacubitril and valsartan tablets (RR 0.85; 95% CI [0.72,1.00]).

Goal-directed medical therapy for Heart Failure with Preserved Ejection Fraction (HFpEF) may include the use of sacubitril and valsartan tablets, which have been shown to have a numerical reduction in the rate of composite endpoint of total HF hospitalizations and CV death 2.

• The treatment effect is primarily driven by the reduction in total HF hospitalizations.
• Key considerations for the use of sacubitril and valsartan tablets in HFpEF include:
  • Starting dosage: 49 mg/51 mg orally twice daily
  • Target maintenance dose: 97 mg/103mg orally twice daily
  • Adjust doses every 2 to 4 weeks to the target maintenance dose, as tolerated by the patient 2

From the Research

Definition and Overview of Goal-Directed Medical Therapy for HFpEF

• Goal-directed medical therapy for Heart Failure with Preserved Ejection Fraction (HFpEF) involves a personalized approach to managing the condition, taking into account the individual patient's symptoms, comorbidities, and underlying pathophysiological mechanisms 3, 4, 5, 6.
• HFpEF is a heterogeneous syndrome characterized by impaired diastolic function, and its management is complicated by the presence of various comorbidities, such as hypertension, diabetes, and renal dysfunction 3, 4, 5, 6.

Pharmacological Therapies for HFpEF

• Currently available pharmacologic therapies for HFpEF include diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers, and beta-blockers 3, 4, 5, 6.
• These therapies can be tailored to individual patient needs, based on their specific symptoms and comorbidities, and can help to improve symptoms, reduce hospitalizations, and enhance quality of life 3, 4, 5, 6.
• Newer therapies, such as mineralocorticoid receptor antagonists, soluble guanylate cyclase stimulators, and angiotensin receptor-neprilysin inhibitors, are being developed and tested in clinical trials, and may offer additional benefits for patients with HFpEF 4, 6.

Importance of Addressing Comorbidities

• Addressing comorbidities, such as hypertension, diabetes, and renal dysfunction, is crucial in the management of HFpEF, as these conditions can contribute to the development and progression of the disease 3, 4, 5, 6.
• Lifestyle modifications, such as sodium and fluid restriction, exercise, and weight loss, can also play an important role in managing HFpEF and reducing the risk of complications 3, 5, 6.

Ongoing Research and Future Directions

• Ongoing research is focused on developing a better understanding of the pathophysiological mechanisms underlying HFpEF, and identifying new therapeutic targets and strategies 3, 4, 6.
• The use of computational statistics and machine learning may help to clarify the pathophysiological substrates of HFpEF and identify potential therapeutic targets 3.
• Future studies will be needed to fully elucidate the benefits and risks of newer therapies for HFpEF, and to determine the optimal approach to managing this complex and heterogeneous condition 4, 6.