Dosing of Entresto in Heart Failure Patients

Clinical Evidence and Guidelines

The American College of Cardiology/American Heart Association recommends sacubitril/valsartan to be administered twice daily in patients with heart failure with reduced ejection fraction (HFrEF), as evidenced by clinical trials demonstrating mortality benefit with twice-daily dosing 1, 2
Clinical trials, such as those published in Circulation and the Journal of the American College of Cardiology, have consistently used twice-daily dosing of sacubitril/valsartan, showing its efficacy in reducing cardiovascular mortality and HF hospitalizations 1, 2, 3
The American College of Cardiology/American Heart Association guidelines specifically list sacubitril/valsartan as requiring twice-daily administration in their tables of recommended medications for HFrEF, with a strength of evidence supporting this recommendation 1, 2, 3

Titration of sacubitril/valsartan should occur every 2-4 weeks in adults, with the goal of achieving target doses shown to be efficacious in reducing cardiovascular mortality and HF hospitalizations, as recommended by the American College of Cardiology 2, 3
Failure to uptitrate to target doses may result in suboptimal outcomes, with only about 27% of patients achieving the target dose within 6 months, according to data from the European Journal of Heart Failure 4, 5

The American College of Cardiology recommends that Entresto tablets should be swallowed whole and not broken, crushed, or split, to ensure proper absorption and efficacy, with absorption occurring primarily in the stomach and proximal small bowel 6

The American College of Cardiology suggests that if a lower dose is needed, commercially available lower-strength tablets should be used rather than splitting higher-strength tablets, with a starting dose of 49/51 mg twice daily and a target dose of 97/103 mg twice daily 7
The American College of Cardiology recommends monitoring blood pressure, heart rate, renal function, and potassium 1-2 weeks after initiation or dose changes, with dose adjustments made by switching to a lower commercially available strength rather than splitting tablets 7

The American College of Cardiology notes that only 27% of patients achieve target dose within 6 months in real-world practice, often due to side effects or slower titration, and recommends managing this by using appropriate tablet strengths, not by splitting 7