Sacubitril+valsartan

ATC code

C09DX04

Therapeutic class

Angiotensin Receptor-Neprilysin Inhibitor (ARNI) · Angiotensin II receptor antagonists, other combinations

Forms

film-coated tablet

Brand names

Entresto (EU)

Overall confidence

high

Regulatory sources consulted

Approved indications

Treatment of symptomatic chronic heart failure with reduced ejection fraction in adult patients.
Treatment of symptomatic chronic heart failure with left ventricular systolic dysfunction in children and adolescents aged one year or older.
First-line therapy for heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality.

Contraindications

Absolute

Concomitant use with ACE inhibitors (ACEi). A 36-hour washout period is required.
History of angioedema related to previous ACEi or ARB therapy.
Pregnancy.
Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (eGFR < 60 ml/min/1.73 m²).

Clinical warnings

Major warning · Risk of angioedema. Higher risk in Black patients. If it occurs, discontinue immediately and do not re-administer. — EMA
Major warning · Hypotension. Risk is greater at treatment initiation or during dose titration. Monitor blood pressure. — EMA
Major warning · Hyperkalemia. Monitor serum potassium, especially in patients with risk factors (renal impairment, diabetes). — EMA

Drug interactions

HighACE Inhibitors (ACEi)C09A
Mechanism: Increased risk of angioedema due to concomitant inhibition of neprilysin (by sacubitril) and increased bradykinin (by ACEi).
Recommendation: Contraindicated. A 36-hour washout period is required between stopping the ACEi and starting sacubitril/valsartan.
EMA SPC
HighAliskirenC09XA02
Mechanism: Dual blockade of the RAAS, increasing the risk of hypotension, hyperkalemia, and renal function deterioration.
Recommendation: Contraindicated in patients with diabetes mellitus or renal impairment (eGFR < 60 ml/min/1.73 m²).
EMA SPC
ModeratePotassium-sparing diureticsC03D
Mechanism: Increased risk of hyperkalemia due to angiotensin II receptor blockade by valsartan and the diuretic's action.
Recommendation: Monitor serum potassium levels frequently, especially at initiation or with dose changes.
EMA SPC

Adverse events

Common (≥1%)

hypotension · hyperkalemia · renal impairment · dizziness · cough

Rare but serious

angioedema · severe hypotension

Pregnancy and lactation

FDA category: Contraindicated

Contraindicated during pregnancy. Can cause fetal harm. Discontinue as soon as pregnancy is detected. Not recommended during lactation.

Recent literature (PubMed)

2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Heidenreich PA, et al. · Circulation · 2022 · Relevance 5/5
Guía clínica de referencia que establece a los inhibidores del receptor de angiotensina y neprilisina (ARNI), como sacubitrilo/valsartán, como terapia fundamental y de primera línea para pacientes con insuficiencia cardíaca con fracción de eyección reducida (ICFEr) para reducir la morbilidad y mortalidad.
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Heidenreich PA, et al. · J Am Coll Cardiol · 2022 · Relevance 5/5
Publicación paralela de la guía de 2022 en JACC, reforzando la recomendación de clase 1 para el uso de ARNI (sacubitrilo/valsartán) en lugar de un IECA o ARA II en pacientes elegibles con ICFEr para mejorar los resultados clínicos.
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Heidenreich PA, et al. · Circulation · 2022 · Relevance 5/5
Resumen ejecutivo de la guía de 2022, que subraya la recomendación central de utilizar sacubitrilo/valsartán como tratamiento de base en la insuficiencia cardíaca con fracción de eyección reducida.
Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.
Shaddy R, et al. · Circulation · 2024 · Relevance 4/5
El ensayo PANORAMA-HF evaluó sacubitrilo/valsartán frente a enalapril en niños con insuficiencia cardíaca. No se encontró una diferencia significativa en el criterio de valoración principal global a las 52 semanas, aunque es el estudio fundamental que respalda su uso en la población pediátrica.
Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression.
Naaman SC, et al. · Diabetes Care · 2023 · Relevance 3/5
Revisión que discute el enfoque de 'pilares terapéuticos' para la nefropatía diabética, haciendo una analogía con el tratamiento de la insuficiencia cardíaca donde sacubitrilo/valsartán es un pilar fundamental. Destaca el rol del fármaco en el continuo cardiorrenal.