From the Guidelines
The most effective new approved medications for heart failure with reduced ejection fraction (HFrEF) include SGLT2 inhibitors like dapagliflozin and empagliflozin, sacubitril/valsartan, vericiguat, and omecamtiv mecarbil, which should be integrated into the established quadruple therapy foundation of beta-blockers, ACE inhibitors/ARBs (or ARNI), mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as recommended by the 2022 AHA/ACC/HFSA guideline 1.
Key Medications for HFrEF
- SGLT2 inhibitors: dapagliflozin (10mg daily) and empagliflozin (10mg daily) reduce hospitalization and mortality by promoting glucose excretion, reducing cardiac workload, and offering cardioprotective effects 1.
- Sacubitril/valsartan (ARNI): started at 24/26mg twice daily and titrated to 97/103mg twice daily as tolerated, combining a neprilysin inhibitor with an ARB 1.
- Vericiguat (soluble guanylate cyclase stimulator): approved for high-risk HFrEF patients at 2.5mg daily, titrated to 10mg daily 1.
- Omecamtiv mecarbil (cardiac myosin activator): improves cardiac contractility at doses of 25-50mg twice daily 1.
Treatment Approach
- Medication selection should be individualized based on comorbidities, side effect profiles, and cost considerations, with gradual introduction and careful monitoring for side effects 1.
- The established quadruple therapy foundation of beta-blockers, ACE inhibitors/ARBs (or ARNI), mineralocorticoid receptor antagonists, and SGLT2 inhibitors should be used as the basis for treatment 1.
- The 2022 AHA/ACC/HFSA guideline provides recommendations for the use of these medications in patients with HFrEF, including starting and target doses, and considerations for individualizing treatment 1.
From the FDA Drug Label
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. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal 1.1 Heart Failure in Adult Patients Ivabradine tablets are indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. To reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with reduced left ventricular ejection fraction.
The new approved medications for heart failure, particularly for patients with Heart Failure with Reduced Ejection Fraction (HFrEF), are:
- Sacubitril-valsartan: indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure, with benefits most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal 2.
- Ivabradine: indicated to reduce the risk of hospitalization for worsening heart failure in adult patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35% 3 3.
From the Research
New Approved Medications for Heart Failure
- Sacubitril/valsartan is a newly approved medication for the treatment of chronic heart failure with reduced ejection fraction (HFrEF) 4, 5, 6, 7, 8.
- It is an angiotensin receptor-neprilysin inhibitor (ARNI) that acts by enhancing the natriuretic peptide system and suppressing the renin-angiotensin-aldosterone system (RAAS) 4, 7.
- The medication has been shown to improve outcomes compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with HFrEF 4, 5, 8.
Benefits of Sacubitril/Valsartan
- Reduces the risk of cardiovascular death or heart failure hospitalization 4, 8.
- Decreases the risk of all-cause death 4, 8.
- Limits the progression of heart failure 4.
- Has a good safety profile, with a comparable safety profile to enalapril 4.
- May exhibit antiarrhythmic properties and reduce the risk of ventricular arrhythmias and sudden cardiac death in patients with HFrEF 6.
Clinical Use of Sacubitril/Valsartan
- Approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction 7.
- Can be used in the acute heart failure setting, enabling a continuum of use in the patient's journey with HFrEF 5.
- Requires careful consideration of dosing and cautions, particularly in patients with hypotension, electrolyte imbalance, and renal insufficiency 5, 7.