Recommended Doses for Heart Failure Medications
Start all four foundational therapies (ACE inhibitor/ARB/ARNI, beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor) within 2-4 weeks at low doses, then uptitrate every 2 weeks to target doses as tolerated.
ACE Inhibitors / ARBs / ARNI
ACE Inhibitors 1, 2
| Drug | Starting Dose | Target Dose |
|---|---|---|
| Captopril | 6.25 mg three times daily | 50-100 mg three times daily |
| Enalapril | 2.5 mg twice daily | 10-20 mg twice daily |
| Lisinopril | 2.5-5.0 mg once daily | 30-35 mg once daily |
| Ramipril | 2.5 mg once daily | 5 mg twice daily or 10 mg once daily |
| Trandolapril | 1.0 mg once daily | 4 mg once daily |
ARBs 2
| Drug | Starting Dose | Target Dose |
|---|---|---|
| Candesartan | 4-8 mg once daily | 32 mg once daily |
| Losartan | 25-50 mg once daily | 50-150 mg once daily |
| Valsartan | 20-40 mg once daily | 160 mg twice daily |
ARNI (Sacubitril/Valsartan) 2, 3
| Starting Dose | Target Dose |
|---|---|
| 49/51 mg twice daily | 97/103 mg twice daily |
- If previously on ACE inhibitor: Allow 36-hour washout before starting ARNI 3
- If ACE inhibitor-naïve or on low-dose ACE/ARB: Start at 24/26 mg twice daily, then uptitrate 3
- Uptitration schedule: Double dose every 2-4 weeks as tolerated 2, 3
Key point: ARNIs are preferred over ACE inhibitors/ARBs when possible, as they provide incremental mortality benefit 2.
Beta-Blockers 1, 2
Only use evidence-based beta-blockers (bisoprolol, carvedilol, or metoprolol succinate) - benefits are NOT a class effect 1.
| Drug | Starting Dose | Target Dose |
|---|---|---|
| Bisoprolol | 1.25 mg once daily | 10 mg once daily |
| Carvedilol | 3.125 mg twice daily | 25-50 mg twice daily |
| Metoprolol succinate (CR/XL) | 12.5-25 mg once daily | 200 mg once daily |
- Uptitration: Double dose at minimum 2-week intervals 1
- Initiate when patient is "dry" (less congested) with adequate heart rate 4
- Do not start in decompensated patients with active signs of congestion 1
Mineralocorticoid Receptor Antagonists 2
| Drug | Starting Dose | Target Dose |
|---|---|---|
| Spironolactone | 12.5-25 mg once daily | 25-50 mg once daily |
| Eplerenone | 25 mg once daily | 50 mg once daily |
- For NYHA class III-IV patients with persistent symptoms despite ACE inhibitor/ARB and beta-blocker 1
- Monitor potassium and creatinine at 2-3 days, then monthly for 3 months 4
- Contraindicated if: K+ >5.0 mmol/L or creatinine >2.5 mg/dL (>221 μmol/L) 1
SGLT2 Inhibitors 4, 2
| Drug | Dose |
|---|---|
| Dapagliflozin | 10 mg once daily |
| Empagliflozin | 10 mg once daily |
- No titration required - single dose 2
- Can be started simultaneously with other foundational therapies 4
- Benefits independent of diabetes status 4
Loop Diuretics 4
- Initial dose depends on: Renal function, prior diuretic exposure, degree of congestion 4
- Titrate to relief of congestion over days to weeks 4
- If requiring high doses (≥80 mg furosemide twice daily): Consider switching loop diuretics, adding thiazide (hydrochlorothiazide/metolazone), or continuous IV infusion 5
Practical Implementation Strategy
Rapid Sequencing Approach 4, 6
Week 0-1: Start beta-blocker + SGLT2 inhibitor simultaneously
Week 1-2: Add ARNI (or ACE inhibitor if ARNI not feasible)
Week 2-4: Add mineralocorticoid receptor antagonist
- ARNIs often better tolerated when patient still "wet" (congested) 4
- Beta-blockers better tolerated when "dry" 4
- All four drugs should be initiated within 2-4 weeks 4
Uptitration Protocol 1, 2
- Double doses every 2 weeks for ACE/ARB/ARNI and beta-blockers 1
- Aim for target doses used in clinical trials 2
- If target not tolerated: Use highest tolerated dose - some drug is better than no drug 1
- Low doses have substantial benefit - achieving low doses of all four classes takes precedence over uptitrating one class to target 4, 6
Monitoring 1, 4
- Blood pressure, heart rate, clinical status at each visit
- Electrolytes and renal function:
- Acceptable creatinine increase: Up to 50% above baseline or to 3 mg/dL (266 μmol/L), whichever is greater 1
- Acceptable potassium: Up to 6.0 mmol/L may be acceptable 1
Common Pitfalls
Asymptomatic hypotension does NOT require dose reduction 1 - only treat if symptomatic (dizziness, lightheadedness, confusion).
Never stop beta-blockers abruptly - risk of rebound ischemia/infarction and arrhythmias 1.
Sequential rather than simultaneous initiation is outdated - modern evidence supports rapid initiation of all four foundational drugs within 2-4 weeks 4, 6.
Waiting months to start all therapies leads to treatment gaps - the conventional 6+ month approach is not evidence-based 6.
Target dosing matters for mortality reduction 2, 7, 8 - higher doses of ACE/ARB/ARNI and beta-blockers reduce all-cause mortality compared to lower doses, though lower doses still provide benefit.