HFrEF

Evidence-based doses of disease-modifying drugs in key randomized trials in patients with heart failure

Drug Class

Starting Dose

Target Dose

ACE-Is

Captopril

6.25 mg t.i.d.

50 mg t.i.d.

Enalapril

2.5 mg b.i.d.

10-20 mg b.i.d.

Lisinopril

2.5-5 mg o.d.

20-35 mg o.d.

Ramipril

1.25-2.5 mg b.i.d.

5 mg b.i.d.

Trandolapril

0.5 mg o.d.

4 mg o.d.

ARNIs

Sacubitril-valsartan

49/51 mg b.i.d.

97/103 mg b.i.d.

ARBs

Candesartan

4 mg o.d.

32 mg o.d.

Losartan

(12.5) 25-50 mg o.d.

150 mg o.d.

Valsartan

40 mg b.i.d.

160 mg b.i.d.

Beta-blockers

Bisoprolol

1.25 mg o.d.

10 mg o.d.

Carvedilol

3.125 mg b.i.d.

25 mg b.i.d.

Metoprolol succinate (CR/XL)

12.5-25 mg o.d.

200 mg o.d.

Nebivolol

1.25 mg o.d.

10 mg o.d.

MRAs

Steroidal

Eplerenone

25 mg o.d.

50 mg o.d.

Spironolactone

12.5-25 mg o.d.

50 mg o.d.

Non-steroidal

Finerenone

10-20 mg o.d.

20-40 mg o.d.

SGLT2-Is

Dapagliflozin

10 mg o.d.

Empagliflozin

10 mg o.d.

Other agents

Digoxin

62.5 µg o.d.

250 µg o.d.

Digitoxin

0.07 mg o.d.

0.1 mg o.d.

Ivabradine

5 mg b.i.d.

7.5 mg b.i.d.

Vericiguat

2.5 mg o.d.

10 mg o.d.

Hydralazine/isosorbide dinitrate

37.5 mg t.i.d./20 mg t.i.d.

75 mg t.i.d./40 mg t.i.d.

Criteria for high risk of advanced heart failure

Rule of three criteria (at least 1):

HFH (≥2 or ≥1 requiring inotropes within the last year)

Diuretic resistance

Intolerance to neurohormonal drugs with onset of cardiorenal syndrome

I NEED HELP criteria (at least 1):

Inotropes

NYHA class III/IV or persistently high natriuretic peptides

End-organ dysfunction (liver, kidney)

EF <20% or poor RV function

Defibrillator shocks

Heart failure hospitalization >1

Escalating diuretics

Low blood pressure, high heart rate

Prognostic medication intolerance or the need to downtitrate

References

1) Køber L, Adamo M, Ruwald AC, Tomasoni D, Anderson LJ, Andersson C, Brugts JJ, Chioncel O, Donal E, Ferdinandy P, Jhund PS, Leyva F, Lorusso R, Madigan M, Mullens W, Paolillo S, Ryan N, Simpson M, Thiele H, Thune JJ, Van Craenenbroeck EM, Van Laake LW, Verbakel M; ESC Guidelines Advisory Group. 2026 ESC Guidelines for the management of heart failure. Eur Heart J. 2026 Aug 28:ehag100. doi: 10.1093/eurheartj/ehag100. Epub ahead of print. PMID: 42661420.