Starting Doses for Heart Failure with LVEF 20-25%
For a patient with severe HFrEF (LVEF 20-25%), initiate lisinopril 2.5-5 mg once daily, metoprolol succinate 12.5-25 mg once daily, spironolactone 25 mg once daily, and dapagliflozin 10 mg once daily, with careful monitoring and gradual uptitration at 2-week intervals. 1
Lisinopril (ACE Inhibitor)
- Start at 2.5-5 mg once daily 1
- Target dose is 20-35 mg once daily 1, 2
- Uptitrate by doubling the dose at minimum 2-week intervals 1
- Check renal function (creatinine, potassium) and blood pressure within 1-2 weeks after initiation and after each dose increase 1, 3
- An increase in creatinine up to 50% above baseline or to 265 μmol/L (3 mg/dL) is acceptable 1
- Potassium up to 5.5 mmol/L is acceptable; if >5.5 mmol/L, halve the dose 1
Metoprolol Succinate (Beta-Blocker)
- Start at 12.5-25 mg once daily 1, 4
- Target dose is 200 mg once daily 1, 4
- Uptitrate by doubling the dose at minimum 2-week intervals 1, 4
- Monitor heart rate, blood pressure, and signs of congestion 1, 5
- Temporary symptomatic deterioration occurs in 20-30% of patients during initiation but can usually be managed by adjusting diuretics 1
- Never stop beta-blockers suddenly due to risk of rebound myocardial ischemia and arrhythmias 1, 3
Spironolactone (Mineralocorticoid Receptor Antagonist)
- Start at 25 mg once daily 1
- Target dose is 25-50 mg once daily, though most patients remain on 25 mg 1, 6
- Critical prerequisite: Verify potassium <5.0 mmol/L and creatinine <221 μmol/L (2.5 mg/dL) before initiation 1, 6
- Check potassium and creatinine at 1 week, 4 weeks, then at 1,2,3, and 6 months 1, 6
- If potassium rises to 5.5-6.0 mmol/L, halve the dose; if >6.0 mmol/L, stop immediately 1, 6
- Spironolactone prevents 57 deaths per 1000 patient-years when added to ACE inhibitors and beta-blockers 1
Dapagliflozin (SGLT2 Inhibitor)
- Start at 10 mg once daily 7, 8, 9
- No titration required—this is both the starting and maintenance dose 7, 9
- Can be initiated regardless of diabetes status 7
- Safe to combine with ACE inhibitors, beta-blockers, and spironolactone 8, 9
- Minimal effect on blood pressure, making it ideal for patients with low BP 1
- Monitor renal function as dapagliflozin slows eGFR decline over time 7
Sequencing Strategy for Low Blood Pressure
Given the severe LVEF (20-25%), this patient may have borderline or low blood pressure. The 2025 ESC consensus recommends initiating SGLT2 inhibitors and MRAs first in patients with low BP, as these have minimal hypotensive effects, followed by beta-blockers, then ACE inhibitors. 1
Recommended initiation sequence for hypotensive patients:
- Start dapagliflozin 10 mg and spironolactone 25 mg simultaneously (minimal BP effect) 1, 8
- Add metoprolol succinate 12.5 mg after 1-2 weeks if heart rate >70 bpm 1
- Add lisinopril 2.5 mg after another 1-2 weeks once tolerating other medications 1, 3
Critical Monitoring Parameters
- Blood pressure and heart rate at each visit 1
- Renal function (creatinine, eGFR) and potassium at 1-2 weeks after any medication initiation or dose change 1, 3, 6
- Signs of congestion (weight gain, edema, dyspnea) requiring diuretic adjustment 1
- Asymptomatic hypotension does not require treatment modification, but symptomatic hypotension warrants reducing non-essential vasodilators or diuretics before reducing guideline-directed medical therapy 1, 3
Common Pitfalls to Avoid
- Do not delay beta-blocker initiation due to low LVEF—these patients benefit most from beta-blockade 4, 5
- Do not combine spironolactone with both an ACE inhibitor and ARB due to excessive hyperkalemia risk 6
- Do not stop uptitration prematurely—aim for target doses or highest tolerated doses, as "some is better than none" but target doses provide optimal mortality benefit 1, 2
- Do not withhold SGLT2 inhibitors in patients already on MRAs—the combination is safe and provides additive benefit 8, 9