The pharmacologic therapies for heart failure with reduced ejection fraction (HFrEF) include several classes of medications, each with specific indications and guidelines for use:
Renin-angiotensin system (RAS) inhibitors
- Angiotensin-converting enzyme inhibitors (ACEIs): ACEIs should reduce morbidity and mortality in patients with previous or current symptoms of chronic HFrEF if the use of angiotensin receptor-neprilysin inhibitors is not feasible
- Angiotensin receptor blockers (ARBs): ARBs are recommended for patients with previous or current symptoms of chronic HFrEF who are intolerant to ACEIs because of cough or angioedema, and if the use of angiotensin receptor-neprilysin inhibitors is not feasible
- Angiotensin receptor-neprilysin inhibitors (ARNi): ARNi should reduce morbidity and mortality in patients with HFrEF and NYHA class II-III symptoms
Beta-blockers
- Beta-blockers: Beta-blockers are recommended for patients with HFrEF with current or previous symptoms, as they provide high economic value
Mineralocorticoid receptor antagonists (MRAs)
- Mineralocorticoid receptor antagonists (MRAs): MRAs should reduce sudden cardiac death and all-cause mortality in patients with HFrEF (LVEF ≤ 40%)
Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors)
- Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors): SGLT-2 inhibitors should reduce the risk of heart failure hospitalization and death in patients with NYHA class II-IV HFrEF (LVEF ≤ 40%)
Other therapies
- Ivabradine: Ivabradine is recommended to reduce the risk of heart failure hospitalization and cardiovascular death in symptomatic patients with LVEF ≤ 35%, in sinus rhythm, and a resting heart rate ≥ 70 bpm despite treatment with a β-blocker, ACEI or angiotensin receptor-neprilysin inhibitor, and a mineralocorticoid receptor antagonist
- Hydralazine and isosorbide dinitrate: This combination is recommended for self-identified Black patients with LVEF ≤ 35% or with an LVEF < 45% combined with a dilated left ventricle in NYHA class III-IV despite treatment with an ACEI (or angiotensin receptor-neprilysin inhibitor), a β-blocker, and a mineralocorticoid receptor antagonist
In summary, the pharmacologic management of heart failure with reduced ejection fraction involves a combination of medications that target different pathways to improve patient outcomes. Core therapies include RAS inhibitors (ACEIs, ARBs, ARNi), beta-blockers, MRAs, and SGLT-2 inhibitors. Additional therapies like ivabradine and the combination of hydralazine and isosorbide dinitrate are utilized in specific patient populations to further reduce morbidity and mortality.