Sacubitril with Valsartan 💊
Related Subjects: Chronic Heart Failure
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Heart Failure and Pulmonary Oedema
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Loop Diuretics
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Entresto Sacubitril with Valsartan
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Angiotensin Converting Enzyme Inhibitors
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Cardiac Resynchronisation Therapy (CRT) Pacemaker
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📖 About
- Always check the BNF for latest prescribing advice ✅
- Fixed-dose combination of sacubitril (neprilysin inhibitor) + valsartan (angiotensin receptor blocker, ARB).
- Recommended for symptomatic HFrEF (LVEF ≤ 35%) with NYHA class II–IV symptoms, already on an ACEI/ARB.
⚙️ Mode of Action
- Sacubitril: inhibits neprilysin → prevents breakdown of natriuretic peptides (ANP, BNP, bradykinin).
- Increased natriuresis, diuresis, vasodilation, ↓ fibrosis & remodelling.
- Valsartan: selectively blocks AT1 receptor → ↓ vasoconstriction, ↓ aldosterone secretion, ↓ afterload.
- Dual action = “ARNI” (Angiotensin Receptor–Neprilysin Inhibitor).
💊 Indication
- Symptomatic chronic HFrEF (NYHA II–IV, LVEF ≤ 35%).
- Patient must be stable on ACEI or ARB before switching.
📈 Dosing (must confirm with BNF/datasheet)
| Formulation | Starting Dose | Frequency | Notes |
|---|
| Entresto | 24/26 mg | BD | Low dose (renal/hepatic impairment, low BP, elderly) |
| Entresto | 49/51 mg | BD | Standard starting dose in most adults |
| Entresto | 97/103 mg | BD | Target dose after 3–4 weeks if tolerated |
🔄 Interactions
- See BNF. Key concern = ACEI overlap (↑ risk of angioedema).
- Monitor with potassium-sparing diuretics, lithium, and NSAIDs.
⚠️ Cautions
- Hypotension (SBP < 100 mmHg) → monitor closely.
- Renal impairment, hyperkalaemia.
- History of angioedema.
🚫 Contraindications
- ACEI use within 36 hrs (must be stopped >36h before starting).
- Concomitant ARB use.
- Severe hepatic impairment.
💥 Side Effects
- Hypotension (common).
- Hyperkalaemia.
- Renal impairment.
- Angioedema (rare but serious).
📚 Key References
📝 Clinical Teaching Pearl
- Switching from ACEI to sacubitril/valsartan requires a washout period of ≥36 hours to avoid angioedema.
- Monitor U&Es, creatinine, BP, and potassium after initiation and titration.
- Now first-line in HFrEF alongside beta-blocker, MRA, and SGLT2 inhibitor in most guidelines.
