Does Entresto Lower Blood Pressure More Than Valsartan?
Yes, Entresto (sacubitril/valsartan) lowers blood pressure more effectively than valsartan alone, with clinically meaningful reductions of approximately 3.9-8.8 mmHg greater systolic BP reduction, particularly in patients with resistant hypertension. 1
Blood Pressure Lowering Efficacy
The evidence demonstrates superior BP-lowering effects of sacubitril/valsartan compared to valsartan monotherapy:
In patients with apparent resistant hypertension and HFpEF, sacubitril/valsartan reduced systolic BP by an additional 4.8 mmHg at 4 weeks and 3.9 mmHg at 16 weeks compared to valsartan alone 1
In patients with apparent MRA-resistant hypertension (those failing valsartan, calcium channel blocker, diuretic, AND mineralocorticoid receptor antagonist), sacubitril/valsartan achieved even greater reductions of 8.8 mmHg at 4 weeks and 6.3 mmHg at 16 weeks versus valsartan 1
The proportion achieving BP control (systolic BP <140 mmHg or <135 mmHg if diabetic) by 16 weeks was 47.9% with sacubitril/valsartan versus only 34.3% with valsartan in resistant hypertension patients (adjusted OR 1.78) 1
Mechanism of Superior Blood Pressure Reduction
The enhanced BP-lowering effect stems from dual mechanisms:
Neprilysin inhibition increases endogenous natriuretic peptides while the valsartan component blocks the angiotensin II receptor, providing complementary pathways for BP reduction 2
Central aortic pressure reduction is superior with sacubitril/valsartan compared to ARB monotherapy, particularly affecting central aortic systolic pressure and nocturnal BP 3
Current Guideline Status and Clinical Context
Important caveat: While sacubitril/valsartan demonstrates superior BP-lowering, the 2024 ESC Guidelines note it "awaits supportive evidence from cardiovascular outcomes trials prior to guideline endorsement for routine use in hypertension" 4, 5
The drug is FDA-approved for heart failure with reduced ejection fraction, not specifically for hypertension treatment 5, 6
The 2022 ESC guidelines note sacubitril/valsartan causes "more symptomatic hypotension than valsartan," requiring careful BP monitoring 4
Cardiovascular Remodeling Benefits Beyond Blood Pressure
Sacubitril/valsartan provides additional benefits that may be partially independent of BP reduction:
Left ventricular mass reduction was significantly greater with sacubitril/valsartan (-6.83 g/m²) versus olmesartan (-3.55 g/m²) at 52 weeks, and this difference remained significant even after adjusting for systolic BP 7
Central pulse pressure showed larger reductions with sacubitril/valsartan compared to olmesartan, suggesting effects beyond peripheral BP lowering 7
Safety Considerations
Monitor closely for:
Symptomatic hypotension occurs more frequently than with valsartan alone 4, 6
Dose adjustment required in patients with creatinine clearance <30 mL/min or moderate hepatic impairment (starting dose 24/26 mg twice daily) 4
Never combine with ACE inhibitors or direct renin inhibitors due to increased risk of adverse events 5
Clinical Bottom Line
For patients with heart failure (particularly HFpEF) and concurrent resistant hypertension, sacubitril/valsartan provides superior BP reduction compared to valsartan alone, with the greatest benefit seen in those with difficult-to-control hypertension despite multiple agents. 1 However, for primary hypertension treatment without heart failure, valsartan or other guideline-recommended agents remain first-line until outcome trials specifically in hypertension populations are completed. 4