From the Guidelines
Heart failure with reduced ejection fraction (HFrEF) should be treated with a combination of medications that improve survival and symptoms, including an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor-neprilysin inhibitor (ARNI), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor, as recommended by the most recent guidelines 1. The cornerstone of therapy includes these four main drug classes, which should be initiated at low doses and gradually titrated to target doses as tolerated.
- An ACEi like lisinopril or enalapril, or an ARNI such as sacubitril/valsartan, is recommended to reduce the risk of HF hospitalization and death 1.
- A beta-blocker such as carvedilol, metoprolol succinate, or bisoprolol is recommended to reduce the risk of HF hospitalization and death 1.
- An MRA like spironolactone or eplerenone is recommended for patients who remain symptomatic despite treatment with an ACEi and a beta-blocker, to reduce the risk of HF hospitalization and death 1.
- An SGLT2 inhibitor such as dapagliflozin or empagliflozin may be considered to reduce the risk of cardiovascular hospitalization and cardiovascular death 1. Diuretics like furosemide are also commonly used to manage fluid overload and symptoms but do not improve mortality.
- For patients with persistent symptoms despite optimal therapy, additional medications such as ivabradine (for those with heart rates ≥70 bpm in sinus rhythm) or hydralazine with isosorbide dinitrate (particularly beneficial in African American patients) may be added 1. These medications work through different mechanisms to reduce cardiac workload, prevent adverse remodeling, decrease neurohormonal activation, and improve cardiac efficiency, collectively leading to improved symptoms, quality of life, and survival in patients with HFrEF.
From the FDA Drug Label
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. Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure.
The medications that can be used to treat Heart Failure with Reduced Ejection Fraction (HFREF) are:
From the Research
Medication Options for HFREF
The following medications have been studied for the treatment of Heart Failure with Reduced Ejection Fraction (HFREF):
- Angiotensin-Converting Enzyme Inhibitors (ACEi) and Angiotensin-Receptor Blockers (ARB) are cornerstones in the treatment of HFREF, as they have been shown to reduce mortality and readmissions 4, 5
- Combined angiotensin receptor antagonists and neprilysin inhibitors have been introduced recently and have further improved the prognosis of patients with HFREF 6
- Beta-receptor blockers and diuretics are also part of the standard treatment for HFREF, although the optimal dosing and timing of these medications are still being studied 7, 8
- Other medications such as ivabradine, levosimendan, omega-3, tolvaptan, recombinant human B-type natriuretic peptide (rhBNP), isosorbide dinitrate and hydralazine (ISDN/HYD) have been investigated, but their effectiveness and optimal use are still being researched 8
Key Considerations
When selecting medications for HFREF, the following factors should be considered:
- The patient's individual characteristics, such as kidney function and blood pressure, which can affect the choice and dosing of medications 7, 4
- The potential benefits and risks of each medication, including the risk of adverse effects and interactions with other medications 8, 5
- The importance of titrating medications to the optimal dose, while also considering the patient's tolerability and potential side effects 7, 6