From the Guidelines
The recommended starting dose of Entresto (sacubitril/valsartan) is 49/51 mg taken twice daily, but for patients with certain conditions such as severe renal impairment (CrCl <30 mL/min) or moderate hepatic impairment, a lower starting dose of 24/26 mg twice daily is recommended. This is based on the most recent and highest quality study available, which emphasizes the importance of careful dosing in patients with specific health conditions 1.
When initiating Entresto, it is crucial to consider the patient's medical history, including previous use of ACE inhibitors or ARBs, as well as their renal function and hepatic status. For patients who have not previously taken an ACE inhibitor or ARB, or those taking low doses of these medications, a lower starting dose may be appropriate. The goal is to balance the benefits of Entresto in reducing morbidity and mortality in heart failure patients with the potential risks, such as hypotension and renal insufficiency 1.
Key considerations for the use of Entresto include:
- Starting dose: 49/51 mg twice daily for most patients, but 24/26 mg twice daily for those with severe renal impairment or moderate hepatic impairment.
- Dose adjustments: Should be made every 2-4 weeks as tolerated, with a target dose of 97/103 mg twice daily.
- Patient monitoring: Regular monitoring of blood pressure, renal function, and potassium levels is essential after initiation of Entresto.
- Concomitant medications: ACE inhibitors should be discontinued at least 36 hours before starting Entresto to avoid the risk of angioedema.
By carefully selecting the starting dose and monitoring patients appropriately, healthcare providers can optimize the benefits of Entresto while minimizing its risks, ultimately improving outcomes for patients with heart failure.
From the Research
Starting Dose of Entresto
The recommended starting dose of Entresto (sacubitril/valsartan) is not explicitly stated in the provided studies. However, the following information can be gathered:
- In the study 2, it is mentioned that the physician may consider starting low-dose atorvastatin at 20 mg daily in combination with sacubitril/valsartan 24 mg/26 mg twice daily and titrating accordingly to optimal doses.
- In the study 3, the initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments.
- Key points to consider when initiating Entresto include:
- The initial dose and titration regimen may vary depending on the patient's condition and tolerability.
- The target dose of sacubitril/valsartan is often 200 mg twice daily, but this may not be achievable for all patients due to various factors such as side effects and medication noncompliance.
- A more gradual initiation/uptitration regimen may maximize attainment of the target dose, especially in patients with low-dose ACEI/ARB.
- Studies 4, 5, and 6 provide additional information on the efficacy and safety of sacubitril/valsartan, but do not specifically address the starting dose.