From the Guidelines
Guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) should include four medication classes: angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i), as recommended by the 2022 AHA/ACC/HFSA guideline 1. The cornerstone medications are ACE inhibitors (such as lisinopril, enalapril) or angiotensin receptor blockers (ARBs, like losartan, valsartan) if ACE inhibitors aren't tolerated, or preferably angiotensin receptor-neprilysin inhibitors (ARNIs) like sacubitril/valsartan.
- Beta-blockers (carvedilol, metoprolol succinate, bisoprolol) are equally important and should be initiated at low doses and gradually titrated up.
- Mineralocorticoid receptor antagonists (spironolactone, eplerenone) should be added for patients who remain symptomatic.
- SGLT2 inhibitors (dapagliflozin, empagliflozin) are now recommended regardless of diabetes status, as they have been shown to reduce the risk of hospitalization and death in patients with HFrEF 1. For symptomatic patients, loop diuretics (furosemide, torsemide) help manage fluid overload.
- In select patients, additional therapies may include ivabradine for those with heart rates ≥70 bpm despite maximized beta-blocker therapy, or hydralazine with isosorbide dinitrate, particularly beneficial in Black patients. These medications work by reducing cardiac workload, inhibiting harmful neurohormonal activation, promoting beneficial remodeling of the heart, and improving cardiac efficiency. Medication doses should be gradually increased to target doses as tolerated, with regular monitoring of blood pressure, heart rate, renal function, and electrolytes. The 2022 AHA/ACC/HFSA guideline provides the most recent and highest quality evidence for the management of HFrEF, and its recommendations should be followed to improve patient outcomes 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.
1 INDICATIONS AND USAGE
1.1 Heart Failure 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 considered guideline-directed medical therapy for heart failure with reduced ejection fraction are:
- Sacubitril and valsartan tablets to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction 2
- Spironolactone tablets to increase survival, manage edema, and reduce the need for hospitalization for heart failure in patients with NYHA Class III-IV heart failure and reduced ejection fraction 3
From the Research
Guideline-Directed Medical Therapy for Heart Failure with Reduced Ejection Fraction
The medications considered guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) include:
- Renin-angiotensin system inhibitors, such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and angiotensin receptor-neprilysin inhibitors (ARNi) 4, 5, 6, 7, 8
- Evidence-based β-blockers (BB) 4, 5, 7
- Mineralocorticoid inhibitors, such as mineralocorticoid receptor antagonists (MRA) 4, 5, 7
- Sodium glucose cotransporter 2 inhibitors (SGLT2i) 4, 5
- Vasodilators, prescribed primarily to Black patients 5
Use of GDMT in HFrEF Patients
The use of GDMT in patients with HFrEF has been associated with improved clinical outcomes, including reduced mortality and hospitalization rates 4, 5, 6, 7, 8. However, there is an underutilization of GDMT in real-world populations, with gaps in use among older patients and those with more comorbidities 5. The initiation and titration of GDMT can be challenging, with hypotension, bradycardia, kidney dysfunction, and hyperkalemia being common causes of underprescription and underdosing 7.
Benefits of GDMT
The benefits of GDMT in patients with HFrEF include: