Does Entresto (sacubitril/valsartan) lower blood pressure?

Does Entresto (Sacubitril/Valsartan) Lower Blood Pressure?

Yes, Entresto (sacubitril/valsartan) effectively lowers blood pressure through its dual mechanism of action as an angiotensin receptor-neprilysin inhibitor (ARNI). 1, 2

Mechanism and Blood Pressure Lowering Effects

• Entresto combines neprilysin inhibition (sacubitril) with angiotensin II receptor antagonism (valsartan), which increases endogenous natriuretic peptides while simultaneously inhibiting the renin-angiotensin-aldosterone system 2
• The valsartan component in Entresto provides significant blood pressure reduction through angiotensin II receptor blockade, with FDA data showing that valsartan alone produces dose-related decreases in systolic and diastolic blood pressure of approximately 6-9/3-5 mmHg at 80-160 mg doses and 9/6 mmHg at 320 mg 1
• Clinical studies have demonstrated that sacubitril/valsartan produces greater blood pressure reduction than valsartan alone, particularly in patients with resistant hypertension 3

Clinical Evidence in Different Populations

• In patients with heart failure and preserved ejection fraction (HFpEF) who had resistant hypertension, sacubitril/valsartan reduced systolic blood pressure by 4.8 mmHg at 4 weeks and 3.9 mmHg at 16 weeks compared to valsartan alone 3
• For patients with apparent mineralocorticoid receptor antagonist (MRA)-resistant hypertension, the blood pressure reduction was even more pronounced: 8.8 mmHg at 4 weeks and 6.3 mmHg at 16 weeks compared to valsartan alone 3
• In maintenance hemodialysis patients with chronic heart failure, sacubitril/valsartan effectively reduced both systolic and diastolic blood pressure before dialysis 4
• Real-world data from hypertensive heart failure patients showed significant reductions in blood pressure (systolic: 12.8 ± 21.2 mmHg, diastolic: 7.1 ± 16.5 mmHg) following sacubitril/valsartan treatment 5

Regulatory Status and Clinical Applications

• While sacubitril/valsartan was initially developed for hypertension, it is currently FDA-approved primarily for reducing hospitalization and risk of cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF) in the United States and Europe 2, 6
• However, it has been approved as an antihypertensive agent in some countries including China and Japan 5
• The 2024 European Society of Cardiology guidelines acknowledge that sacubitril/valsartan has BP-lowering properties but note that it awaits supportive evidence from cardiovascular outcomes trials prior to guideline endorsement for routine use in hypertension 6

Potential Benefits in Specific Hypertension Phenotypes

• Sacubitril/valsartan may be particularly effective for age-related hypertension phenotypes such as resistant hypertension characterized by systolic (central) hypertension and/or nocturnal hypertension 7
• In patients with apparent resistant hypertension, 47.9% achieved controlled systolic blood pressure by Week 16 with sacubitril/valsartan compared to 34.3% with valsartan alone 3
• For those with apparent MRA-resistant hypertension, blood pressure control rates were 43.6% with sacubitril/valsartan versus 28.4% with valsartan alone 3

Safety Considerations

• The most common side effect of sacubitril/valsartan is hypotension, which requires monitoring, particularly when initiating therapy 2
• In hemodialysis patients, there was an increased incidence of hyperkalemia during sacubitril/valsartan treatment, highlighting the need for electrolyte monitoring in certain populations 4
• Like other agents affecting the renin-angiotensin system, sacubitril/valsartan should not be combined with ACE inhibitors or direct renin inhibitors due to increased risk of adverse events 8

In conclusion, Entresto (sacubitril/valsartan) demonstrates significant blood pressure-lowering effects through its dual mechanism of action, with evidence showing superior blood pressure reduction compared to valsartan alone, particularly in patients with resistant hypertension.