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Sacubitril + Valsartan

Angiotensin receptor-neprilysin inhibitor (ARNI)

ATC code: C09DX04(Sacubitril and valsartan)

Updated · Methodology

Indications

A

Heart failure with reduced ejection fraction

First line

Heart failure with reduced ejection fraction (≤40%) in adults. Per HF 2021 and //HFSA 2022, ARNI is part of foundational quadruple therapy with a beta-blocker, MRA, and SGLT2 inhibitor. ACEi/ARB-naïve patients start at 49/51 mg twice daily; patients switching from enalapril require a 36-hour washout (angioedema risk). Up-titrate to 97/103 mg twice daily over 2–4 weeks with BP and K+ monitoring.

Sources

  1. AEMPS: Ficha técnica de Sacubitrilo + Valsartán (2024)
  2. ESC: 2021 ESC Guidelines for heart failure (2021)

ICD-10: I50.1 · ICD-11: BD11.2

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Hypertension

Not recommended

Sacubitril/valsartan is frequently marketed as a blood-pressure drug and prescribed for essential hypertension without heart failure. Per AEMPS, , and , the licensed indication is only HFrEF; for isolated hypertension the drug is not approved. The Spanish cost is €80–120/month, whereas enalapril + amlodipine + indapamide give comparable BP control for €5-10. If it was prescribed for high blood pressure without a documented HFrEF diagnosis (echocardiogram with EF ≤40%, or ≤50% with symptoms), consider getting a second opinion and an echocardiogram.

Sources

  1. AEMPS: Ficha técnica de Sacubitrilo + Valsartán (2024)
  2. ESC: 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. (2024)

ICD-10: I10 · ICD-11: BA00

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Sacubitril is a prodrug; the active metabolite LBQ657 blocks neprilysin, raising natriuretic peptide levels (BNP, ANP, CNP), enhancing natriuresis, diuresis, and vasodilation. Valsartan blocks AT1 receptors of angiotensin II in parallel and offsets the angiotensin II rise from neprilysin blockade. PARADIGM-HF (NEJM 2014): in HFrEF, a 20% reduction in the composite of death and hospitalizations vs enalapril.

Safety

Contraindications

  • Hypersensitivity
  • History of ACEi or ARB angioedema
  • Concomitant ACE inhibitor
  • Pregnancy (2nd-3rd trimester)
  • Severe hepatic impairment, biliary cirrhosis, cholestasis
  • Concomitant aliskiren in diabetes or CrCl <60

Serious adverse effects

  • Angioedema (higher risk in Black patients)
  • Severe hypotension with AKI
  • Severe hyperkalemia

Common adverse effects

  • Hypotension (especially at initiation)
  • Hyperkalemia
  • Elevated creatinine
  • Dizziness
  • Cough

Pregnancy: can you take Sacubitril + Valsartan?

Contraindicated from the 2nd trimester (fetopathy). When pregnancy is planned, discontinue in advance and switch to a beta-blocker or hydralazine under cardiology supervision.

Breastfeeding: can you take Sacubitril + Valsartan?

Milk excretion data are unavailable. During breastfeeding switch to a beta-blocker (metoprolol) or short-acting ACE inhibitor (captopril, enalapril) that are safe during lactation.

Calculate RIDFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Monitoring

Creatinine, K+, and BP at 1–2 weeks after start and each titration, then every 6 months. NT-proBNP is no longer reliable (rises with neprilysin blockade) – follow BNP, echocardiogram, and symptoms instead.

Drug interactions

Do not combine with an ACE inhibitor – 36-hour washout required. Do not combine with another ARB or with aliskiren in diabetes or CrCl <60.

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Frequently asked

What is Sacubitril + Valsartan used for?

Sacubitril + Valsartan is evaluated for the following indications with varying evidence strength: Heart failure with reduced ejection fraction (evidence tier A), Hypertension (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Sacubitril + Valsartan?

Common side effects of Sacubitril + Valsartan (≥ 1 in 100): Hypotension (especially at initiation), Hyperkalemia, Elevated creatinine, Dizziness, Cough. See the Safety section for uncommon and serious reactions.

Is Sacubitril + Valsartan safe during pregnancy?

Contraindicated from the 2nd trimester (fetopathy). When pregnancy is planned, discontinue in advance and switch to a beta-blocker or hydralazine under cardiology supervision.

Is Sacubitril + Valsartan compatible with breastfeeding?

Milk excretion data are unavailable. During breastfeeding switch to a beta-blocker (metoprolol) or short-acting ACE inhibitor (captopril, enalapril) that are safe during lactation.

Who should not take Sacubitril + Valsartan?

Sacubitril + Valsartan is contraindicated in: Hypersensitivity; History of ACEi or ARB angioedema; Concomitant ACE inhibitor; Pregnancy (2nd-3rd trimester); Severe hepatic impairment, biliary cirrhosis, cholestasis. Full list in the Safety section.

Other drugs in this group

Telmisartan, Telmisartan + Hydrochlorothiazide, Valsartan, Valsartan + Hydrochlorothiazide, Amlodipine + Olmesartan, Azilsartan medoxomil + chlorthalidone, Enalapril, Losartan