Sacubitril + Valsartan is a medicine prescribed for the treatment of chronic heart failure. It combines Sacubitril, which enhances the body’s natural peptides to relax blood vessels and reduce fluid buildup, with Valsartan, which blocks the effects of angiotensin II to lower blood pressure and protect the heart. Working together, these ingredients improve the heart’s ability to pump blood, ease symptoms such as breathlessness and swelling, and reduce the risk of hospitalisation or serious heart-related complications.

Sacubitril + Valsartan is a prescription medicine used in the treatment of chronic heart failure, a condition in which the heart cannot pump blood efficiently enough to supply the body with oxygen and nutrients. It combines two active substances, Sacubitril and Valsartan, which work together to improve heart function and reduce the risk of worsening heart failure.

Sacubitril increases the levels of specific natural peptides in the body. These peptides help relax blood vessels, promote the excretion of sodium and water, and reduce strain on the heart. Valsartan is an angiotensin II receptor blocker (ARB) that prevents the effects of angiotensin II, a hormone that causes blood vessels to tighten and retain fluid. By blocking this hormone, Valsartan lowers blood pressure and protects the heart from further damage. Together, Sacubitril and Valsartan make it easier for the heart to pump blood, relieve symptoms such as swelling and shortness of breath, and lower the risk of hospitalisation or serious cardiovascular events.

The medicine is usually taken twice daily, and it is important to follow your doctor’s instructions carefully. Regular monitoring is required while on this treatment. Your doctor will check blood pressure, kidney function, and potassium levels to ensure the medicine is safe and effective for you. You should promptly report any unusual symptoms such as dizziness, swelling of the face or legs, or extreme tiredness. This medicine must not be taken at the same time as an angiotensin-converting enzyme (ACE) inhibitor, as combining them can increase the risk of serious side effects, including angioedema.

Sacubitril + Valsartan is most effective when used alongside lifestyle measures recommended by your doctor. These include following a low-salt diet, engaging in regular physical activity appropriate for your condition, and taking other prescribed heart medications consistently. Together, these measures help improve quality of life and reduce the risk of further heart problems.

Sacubitril + Valsartan is indicated for:

• Chronic Heart Failure with Reduced Ejection Fraction (HFrEF): Used to reduce the risk of cardiovascular death and heart failure hospitalisation.

• Pediatric Heart Failure: Used in children one year of age and older with symptomatic systemic left ventricular systolic dysfunction (use is highly specialised).

• Replacement Therapy: Used as a replacement for an ACE inhibitor or ARB in appropriate chronic heart failure patients.

• Superior Mortality Reduction: Studies have shown that Sacubitril + Valsartan is more effective than the standard ACE inhibitor, enalapril, at reducing cardiovascular death and hospitalisation rates in HFrEF patients.
• Reduces Cardiac Strain: The combination of vasodilation, salt excretion, and reduced Angiotensin II activity decreases the workload on the heart (reduced preload and afterload).
• Reverse Cardiac Remodelling: By blocking pathological neurohormones and enhancing protective ones, it helps slow or potentially reverse the process of ventricular hypertrophy (thickening) and fibrosis (scarring) that occurs in chronic heart failure.
• Improved Quality of Life: Patients often experience improvements in symptoms such as shortness of breath and fatigue, leading to a better quality of life and improved functional capacity.

When taken as directed, Sacubitril + Valsartan is generally safe. Side effects are usually rare, mild, and temporary.

Common Side Effects (Rare):

• Nausea and Vomiting
• Constipation
• Stomach upset
• Slight drowsiness
• Symptomatic Hypotension: Low blood pressure, causing dizziness or lightheadedness, especially when standing up quickly.
• Hyperkalemia: Elevated potassium levels in the blood, which require regular blood tests.
• Dizziness or Vertigo.
• Cough.

Serious Side Effects (Stop taking the medicine and seek urgent medical attention if you experience):

• Severe Allergic Reaction (Angioedema): Rash, swelling of the face, throat, or tongue, difficulty breathing, or dizziness.
• Serious Skin Reactions (Very Rare): Redness, blistering, peeling of the skin (e.g., Stevens-Johnson Syndrome).
• Signs of Liver Damage (Overdose Risk): Yellowing of the skin or eyes (jaundice), persistent nausea, unexplained fatigue, or pain in the upper right abdomen.
• Signs of Severe Hypotension: Profound lightheadedness, fainting, or inability to stand.
• Acute Kidney Injury: Sudden or severe deterioration in kidney function, often with reduced urination or fatigue.

• Dosage: The starting dose is usually low (e.g., 24mg/26mg twice daily) and gradually titrated upwards by the physician every 2 to 4 weeks, based on the patient's tolerability and blood pressure response, up to the maximum maintenance dose.
• Administration: The tablet should be swallowed whole, with or without food, twice daily (e.g., once in the morning and once in the evening).
• Crucial Washout Period: If a patient is currently taking an ACE inhibitor (e.g., Enalapril, Lisinopril), they MUST stop the ACE inhibitor for a 36-hour washout period before starting Sacubitril + Valsartan to prevent the risk of angioedema. This step is critical.

Sacubitril + Valsartan acts by simultaneously modulating two major neurohormonal systems involved in the progression of heart failure:

1. RAAS Blockade (Valsartan): Valsartan competitively blocks Angiotensin II from binding to its AT1 receptor. This prevents Angiotensin II from causing vasoconstriction, fluid retention, and adverse cardiac remodelling (fibrosis). [Image illustrating Angiotensin II receptor blockade leading to vasodilation]
2. Neprilysin Inhibition (Sacubitrilat): Sacubitrilat inhibits the Neprilysin enzyme. Neprilysin's job is to degrade beneficial vasodilators, primarily the Natriuretic Peptides (NPs). By stopping this degradation, NPs (like BNP) accumulate, leading to enhanced beneficial effects: vasodilation, reduced sympathetic tone, natriuresis (salt excretion), and diuresis (water excretion). [Image illustrating Neprilysin inhibition leading to increased Natriuretic Peptides (NPs)]

The net effect is a powerful counter-regulation of the harmful neurohormonal activation that drives heart failure progression.

• Dose Titration: Be patient during the dose titration (upward adjustment) phase. Your doctor will slowly increase the dose to ensure your blood pressure remains safe and stable.
• Hypotension Watch: Get up slowly when moving from a sitting or lying position to avoid dizziness or fainting caused by low blood pressure.
• No ACE Inhibitors: It is essential to understand and respect the 36-hour gap if you are switching from an ACE inhibitor. Inform every healthcare provider that you are on this specific medication.
• Monitor Potassium: You will need regular blood tests to check your potassium and kidney function, especially when starting the medication or changing the dose.

• Store the tablets in the original blister packaging at room temperature (typically below 30 °C / 86 °F), away from moisture and heat.
• Do not divide, crush, or chew the tablets.

• Potassium-Rich Foods: Caution is advised. Due to the risk of hyperkalemia (high potassium) associated with the ARB component (Valsartan), large quantities of potassium-rich foods (e.g., bananas, spinach, citrus juices, potassium-containing salt substitutes) should be consumed only with medical guidance.
• Grapefruit Juice: No known major interaction.

• ACE Inhibitors: CONTRAINDICATED. Requires a 36-hour washout period between the last dose of an ACE inhibitor and the first dose of Sacubitril + Valsartan.
• Other Angiotensin Receptor Blockers (ARBs): Should not be co-administered.
• Potassium-Sparing Diuretics (e.g., Spironolactone, Amiloride) and Potassium Supplements: Increases the risk of severe hyperkalemia (high potassium). Frequent monitoring is essential.
• NSAIDs (e.g., Ibuprofen, Naproxen) and COX-2 Inhibitors: Concurrent use, especially in elderly or volume-depleted patients, may worsen kidney function, including possible acute renal failure.
• Lithium: Concurrent use may increase serum lithium concentrations and toxicity.

• Angioedema History: CONTRAINDICATED in patients with a history of angioedema related to previous ACE inhibitor or ARB use.
• Severe Renal Impairment: Requires dose adjustment and frequent monitoring.
• Hepatic Impairment: Requires dose adjustment.
• Bilateral Renal Artery Stenosis: Should be used with extreme caution, as RAAS inhibitors can severely worsen kidney function.

The target maintenance dose is typically 97mg/103mg (one tablet twice daily). However, the initial dose is often 24mg/26mg (one tablet twice daily) and is increased gradually under strict medical supervision.

The most likely manifestation of overdose is severe hypotension (profoundly low blood pressure) and possibly hyperkalemia.

Action Required: If an overdose is suspected, immediately seek emergency medical assistance. Management typically involves supportive care, lying the patient down with legs elevated, and potentially IV fluid administration.

If you miss a dose, take it as soon as you remember. However, if it is more than 6 hours past your scheduled time, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time to make up for the missed one.