What are the recommended dosages for Angiotensin-Converting Enzyme (ACE) inhibitors, beta-blockers, Mineralocorticoid Receptor Antagonists (MRAs), and Sodium-Glucose Cotransporter 2 inhibitors (SGLT2is) in the treatment of Heart Failure with reduced Ejection Fraction (HFrEF)?

Recommended Dosages for HFrEF Medications

The recommended dosages for ACE inhibitors, beta-blockers, MRAs, and SGLT2 inhibitors in HFrEF treatment include starting with low doses and titrating to target doses that have demonstrated mortality benefits in clinical trials. 1

ACE Inhibitors

Medication	Initial Daily Dose	Target Dose	Mean Dose in Trials
Captopril	6.25 mg TID	50 mg TID	122.7 mg/day
Enalapril	2.5 mg BID	10-20 mg BID	16.6 mg/day
Lisinopril	2.5-5 mg QD	20-40 mg QD	32.5-35.0 mg/day
Ramipril	1.25-2.5 mg QD	10 mg QD	N/A
Trandolapril	1 mg QD	4 mg QD	N/A

Angiotensin Receptor Blockers (ARBs)

For patients intolerant to ACE inhibitors due to cough or angioedema

Medication	Initial Daily Dose	Target Dose	Mean Dose in Trials
Candesartan	4-8 mg QD	32 mg QD	24 mg/day
Losartan	25-50 mg QD	50-150 mg QD	129 mg/day
Valsartan	20-40 mg BID	160 mg BID	254 mg/day

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

Preferred over ACE inhibitors/ARBs in NYHA class II-III

Medication	Initial Daily Dose	Target Dose	Mean Dose in Trials
Sacubitril/valsartan	49/51 mg BID	97/103 mg BID	182/193 mg/day

Beta-Blockers

Medication	Initial Daily Dose	Target Dose	Mean Dose in Trials
Bisoprolol	1.25 mg QD	10 mg QD	8.6 mg/day
Carvedilol	3.125 mg BID	25-50 mg BID	37 mg/day
Metoprolol succinate	12.5-25 mg QD	200 mg QD	159 mg/day

Mineralocorticoid Receptor Antagonists (MRAs)

Medication	Initial Daily Dose	Target Dose	Mean Dose in Trials
Spironolactone	12.5-25 mg QD	25-50 mg QD	26 mg/day
Eplerenone	25 mg QD	50 mg QD	42.6 mg/day

SGLT2 Inhibitors

Medication	Initial Daily Dose	Target Dose	Mean Dose in Trials
Dapagliflozin	10 mg QD	10 mg QD	9.8 mg/day
Empagliflozin	10 mg QD	10 mg QD	N/A

Medication Initiation and Titration Algorithm

1. Start with low doses of all medications as indicated in the tables above 1
2. Uptitrate gradually every 2-4 weeks as tolerated toward target doses 1
3. Monitor closely for adverse effects during titration:
   • Blood pressure and postural changes
   • Renal function (creatinine, eGFR)
   • Electrolytes (particularly potassium)
   • Heart rate (especially with beta-blockers)

Important Clinical Considerations

• Target doses matter: Clinical trials demonstrating mortality benefits used specific target doses. Higher doses of ACEIs and ARBs reduce the risk of HF worsening compared to lower doses 2
• Prioritize tolerance over speed: If a patient cannot tolerate target doses, maintain the highest tolerated dose rather than discontinuing therapy
• MRA precautions: Only use if eGFR >30 mL/min/1.73m² and serum potassium <5.0 mEq/L 1
• SGLT2i dosing simplicity: Unlike other medication classes, SGLT2 inhibitors typically start and remain at the same dose without titration 1

Common Pitfalls to Avoid

1. Underdosing: Many patients in clinical practice receive lower doses than those proven effective in clinical trials
2. Premature discontinuation: Temporary side effects during uptitration often resolve with time
3. Inadequate monitoring: Failure to check renal function and electrolytes during titration
4. Neglecting combination therapy: The 2022 AHA/ACC/HFSA guidelines recommend using all four medication classes (ARNI/ACEi/ARB, beta-blocker, MRA, and SGLT2i) for optimal outcomes 1
5. Excessive hypotension: Starting multiple agents simultaneously at high doses can cause symptomatic hypotension

By following these dosing recommendations and titration strategies, clinicians can optimize GDMT for patients with HFrEF to reduce mortality, hospitalizations, and improve quality of life.