Angiotensin receptor-neprilysin inhibitor (ARNI)
ATC code: C09DX04 (Sacubitril and valsartan)
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.
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.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
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.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Contraindicated from the 2nd trimester (fetopathy). When pregnancy is planned, discontinue in advance and switch to a beta-blocker or hydralazine under cardiology supervision.
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.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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.
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.
FDA category D. Contraindicated from the 2nd trimester (fetopathy). When pregnancy is planned, discontinue in advance and switch to a beta-blocker or hydralazine under cardiology supervision.
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.
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.