ARNI — Angiotensin Receptor–Neprilysin Inhibitor Pregnancy: Contraindicated in second/third trimester — fetal renal toxicity (ARB component). First trimester: avoid.

Sacubitril/Valsartan (Elderly HFrEF)

Brand names: Entresto

Adult dose

Dose: Starting dose (elderly/ACEi-naive): 24/26 mg twice daily; target dose: 97/103 mg twice daily (double every 2–4 weeks as tolerated)

Route: Oral

Frequency: Twice daily

Max: 97/103 mg twice daily

Geriatric-specific: start at lower dose (24/26 mg BD) — elderly are more susceptible to hypotension and renal impairment. Must stop ACE inhibitor 36 hours before starting (angioedema risk if combined). Recommended over ACEi/ARB in HFrEF (EF ≤40%) by ESC 2021 and NICE NG106.

Paediatric dose

Route:

Not licensed in paediatrics.

Dose adjustments

Renal

No dose adjustment for eGFR >30 mL/min. Avoid if eGFR <30. Monitor creatinine and potassium closely in elderly with CKD.

Hepatic

Avoid in severe hepatic impairment (Child-Pugh C). Moderate impairment: start at 24/26 mg BD.

Clinical pearls

PARADIGM-HF (McMurray et al. NEJM 2014): sacubitril/valsartan vs enalapril — 20% relative risk reduction in CV death or HF hospitalisation; ARNI was superior. Elderly subgroup analysis confirmed similar benefits in those ≥65 years, though hypotension more common
TRANSITION trial (2018): initiation of sacubitril/valsartan in-hospital (post-acute HF) vs after stabilisation — in-hospital start safe and feasible; MHRA guidance supports early initiation after acute decompensation once haemodynamically stable
Key geriatric consideration: start at 24/26 mg BD in elderly, frail, or eGFR 30–60 patients — slower uptitration tolerated; many elderly achieve 49/51 mg BD as maximum tolerated dose (acceptable if 97/103 mg not tolerated)

Contraindications

Within 36 hours of ACE inhibitor use (angioedema risk)
History of hereditary angioedema
eGFR <30 mL/min
Severe hepatic impairment
Second/third trimester of pregnancy

Side effects

Hypotension (particularly first doses in elderly — take with sitting/lying position)
Hyperkalaemia (monitor K+ in CKD)
Renal impairment
Cough (less than ACEi — valsartan component)
Angioedema (rare but increased vs ARB alone — neprilysin inhibition)
Dizziness

Interactions

ACE inhibitors (NEVER combine — 36-hour washout mandatory; angioedema risk)
Potassium-sparing diuretics and supplements (hyperkalaemia)
NSAIDs (worsens renal function and fluid retention in elderly HF)

Monitoring

BP (before and 2 hours after each dose increase)
Serum creatinine and eGFR (at 1–2 weeks after each increase)
Serum potassium (hyperkalaemia risk — target K+ <5.5 mmol/L)
Symptoms of angioedema (facial swelling, lip swelling, tongue — emergency)

Reference: BNFc; BNF 90; PARADIGM-HF Trial (NEJM 2014); NICE NG106 (Chronic Heart Failure); ESC Heart Failure Guidelines 2021; MHRA SPC Entresto. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways