From the Guidelines
The four pillars of heart failure treatment are ACE inhibitors (or ARBs/ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors, all of which have been shown to reduce mortality and hospitalizations in heart failure with reduced ejection fraction, as outlined in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
Key Medications and Doses
The following medications and doses are recommended:
- ACE inhibitors:
- Lisinopril 20-40mg daily
- Enalapril 10-20mg twice daily
- Ramipril 10mg once daily, as per the initial and target doses listed in the guideline 1
- ARBs:
- Valsartan 160mg twice daily
- Candesartan 32mg daily
- ARNI:
- Sacubitril/valsartan 97/103mg twice daily, which is preferred when possible, as it has been shown to have benefits in clinical trials 1
- Beta-blockers:
- Carvedilol 25-50mg twice daily
- Metoprolol succinate 200mg daily
- Bisoprolol 10mg daily, with the goal of achieving the target doses outlined in the guideline 1
- MRAs:
- Spironolactone 25-50mg daily
- Eplerenone 50mg daily, as these medications have been shown to block aldosterone effects and improve outcomes in heart failure patients 1
- SGLT2 inhibitors:
- Dapagliflozin 10mg daily
- Empagliflozin 10mg daily, which have been shown to improve cardiac energetics and reduce cardiac remodeling 1
Titration and Monitoring
Patients should be started on lower doses and titrated up gradually while monitoring blood pressure, heart rate, renal function, and potassium levels to achieve these target doses safely, as recommended in the guideline 1.
Mechanisms of Action
These medications work through different mechanisms:
- ACE inhibitors/ARBs block harmful neurohormonal activation
- Beta-blockers reduce cardiac workload
- MRAs block aldosterone effects
- SGLT2 inhibitors improve cardiac energetics and reduce cardiac remodeling, all of which contribute to reducing mortality and hospitalizations in heart failure with reduced ejection fraction, as supported by the evidence from the 2022 AHA/ACC/HFSA guideline 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Four Pillars of Heart Failure
The four pillars of medical therapy in heart failure with reduced ejection fraction (HFrEF) include:
- Sodium-glucose co-transporter-2 inhibitors
- Beta-blockers
- Mineralocorticoid receptor antagonists
- Angiotensin-converting enzyme inhibitors or angiotensin receptor-nephrilysin inhibitors 2, 3, 4, 5
Ideal Doses
The ideal doses of these medications are not explicitly stated in the provided studies, but it is recommended to start with low doses and titrate up as tolerated 6. The studies suggest that higher doses of ACE inhibitors, angiotensin-2 receptor blockers, and beta-blockers may reduce the risk of heart failure worsening and hospitalization, but may also increase the risk of adverse effects such as hypotension, dizziness, and hyperkalemia 6.
Key Findings
- The simultaneous initiation of the four pharmacological pillars at discharge after a decompensation event may provide prognostic advantages 4
- Renal dysfunction is a common condition that limits the use of the four-pillar approach 4
- The use of ≥2 drugs is associated with a lower risk of rehospitalization during the 30 days after discharge 4
- Higher doses of ACE inhibitors and ARBs reduce the risk of heart failure worsening compared to lower doses, but increase the risk of adverse effects 6