Entresto (Sacubitril/Valsartan) is NOT Recommended for Hypertension Alone
Entresto should not be used as first-line treatment for patients with hypertension alone without heart failure. The drug is specifically indicated for heart failure with reduced ejection fraction (HFrEF), not isolated hypertension, despite its blood pressure-lowering properties 1.
Current Guideline-Directed Indications
Heart Failure, Not Hypertension Alone
Sacubitril/valsartan is indicated for treatment of HFrEF as an alternative to ACE inhibitors or ARBs in hypertensive populations who have established heart failure 1.
The 2022 AHA/ACC/HFSA guidelines clearly state that sacubitril/valsartan is approved for symptomatic heart failure (NYHA class II-IV) with reduced ejection fraction, not for hypertension alone 1.
The 2024 ESC guidelines acknowledge that sacubitril/valsartan was initially developed for hypertension and has BP-lowering properties, but explicitly state it "awaits supportive evidence from cardiovascular outcomes trials prior to guideline endorsement and routine use in hypertension" 1.
First-Line Treatment for Hypertension Alone
What You Should Use Instead
For uncomplicated hypertension, the first-line agents are: ACE inhibitors, ARBs, dihydropyridine calcium channel blockers, and thiazide/thiazide-like diuretics 1.
Combination therapy with two of these major drug classes (preferably as single-pill combinations) is recommended for most patients with confirmed hypertension (BP ≥140/90 mmHg) 1.
The preferred initial combinations are: RAS blocker (ACE inhibitor or ARB) with either a calcium channel blocker or a thiazide/thiazide-like diuretic 1.
Why Entresto Is Not Appropriate for Hypertension Alone
Evidence Gap
While sacubitril/valsartan demonstrates BP-lowering efficacy in clinical trials 2, 3, there are no cardiovascular outcomes data from prospective trials proving benefit in isolated hypertension 1.
The landmark PARADIGM-HF trial that established sacubitril/valsartan's superiority was conducted in patients with HFrEF, not hypertension alone 1, 4.
Regulatory Status
Sacubitril/valsartan has been approved as an antihypertensive agent only in China and Japan, but not in Europe or the USA for treating hypertension 3.
Current FDA labeling restricts its use to heart failure with reduced ejection fraction 1.
When Entresto Becomes Appropriate
Specific Clinical Scenarios
Use sacubitril/valsartan when a patient has both hypertension AND heart failure with reduced ejection fraction (LVEF typically ≤40%) 1.
The patient should remain symptomatic (NYHA class II-IV) despite guideline-directed medical therapy 1, 4.
In real-world practice, approximately 38% of HFrEF patients on optimized therapy remain eligible for sacubitril/valsartan introduction 5.
Practical Algorithm for Your Patient
If Hypertension Alone (No Heart Failure):
- Start with combination therapy: ACE inhibitor or ARB + calcium channel blocker OR thiazide/thiazide-like diuretic 1
- Target BP <130/80 mmHg (or <140/80 in elderly) 1
- Use single-pill combinations to improve adherence 1
- If uncontrolled, escalate to triple therapy (RAS blocker + CCB + diuretic) 1
If Hypertension WITH Heart Failure:
- Confirm HFrEF (LVEF ≤40%) and symptomatic status (NYHA ≥II) 1
- Replace ACE inhibitor or ARB with sacubitril/valsartan 1
- Start at low dose (24/26 mg or 49/51 mg twice daily) and titrate to target dose (97/103 mg twice daily) 1
- Monitor for hypotension, especially if systolic BP ≤100 mmHg at baseline 1
Critical Caveats
Do not use sacubitril/valsartan simply because a patient has difficult-to-control hypertension without documented heart failure 1.
The drug's cost is substantially higher than standard antihypertensive agents, and insurance coverage for hypertension alone would likely be denied 2.
While research shows BP-lowering effects 2, 3, 6, guidelines prioritize morbidity and mortality outcomes, which have only been demonstrated in heart failure populations 1, 4.