When should I switch a patient with uncontrolled hypertension from benazapril (Angiotensin-Converting Enzyme (ACE) inhibitor) to Entresto (sacubitril/valsartan)?

Switching from Benazepril to Entresto for Uncontrolled Hypertension

Do not switch from benazepril to Entresto (sacubitril/valsartan) for the primary indication of uncontrolled hypertension alone—Entresto is indicated specifically for heart failure with reduced ejection fraction (HFrEF), not as a first-line or alternative treatment for hypertension. 1, 2

When Entresto IS Indicated

Switch to Entresto only if your patient has both:

• Heart failure with reduced ejection fraction (HFrEF) with NYHA class II-IV symptoms 1, 2
• Current treatment with an ACE inhibitor or ARB that needs optimization for heart failure outcomes 1, 3

In this specific scenario, Entresto is indicated as a replacement for ACE inhibitors or ARBs because it reduces cardiovascular death and heart failure hospitalization more effectively than enalapril in HFrEF patients 2, 3. The 2020 International Society of Hypertension guidelines explicitly state that sacubitril-valsartan (ARNI) is indicated for treatment of HFrEF as an alternative to ACE inhibitors or ARBs, including in hypertensive populations 4.

Critical Switching Requirements

If switching from benazepril to Entresto is appropriate (i.e., patient has HFrEF):

• Mandatory 36-hour washout period between stopping benazepril and starting Entresto to avoid angioedema risk 1
• Starting dose: 49/51 mg twice daily, titrating to target 97/103 mg twice daily after 2-4 weeks as tolerated 1
• Contraindications: History of angioedema with ACE inhibitors, concomitant ACE inhibitor use, hypersensitivity 1

What to Do for Uncontrolled Hypertension Instead

For uncontrolled hypertension on benazepril alone, the evidence-based approach is:

• Add a calcium channel blocker (amlodipine 5-10 mg daily) as the second agent, providing complementary vasodilation to RAS blockade 4
• Alternative: Add a thiazide-like diuretic (chlorthalidone 12.5-25 mg or hydrochlorothiazide 25 mg daily) for volume-dependent hypertension 4
• Target blood pressure: <130/80 mmHg for most patients, minimum <140/90 mmHg 4

If blood pressure remains uncontrolled on dual therapy:

• Add a third agent to create the guideline-recommended triple therapy: ACE inhibitor + calcium channel blocker + thiazide diuretic 4
• Preferably use single-pill combinations to improve adherence 4

If blood pressure remains uncontrolled on optimized triple therapy (resistant hypertension):

• Add spironolactone 25-50 mg daily as the preferred fourth-line agent 4
• Rule out secondary hypertension (primary aldosteronism, renal artery stenosis, obstructive sleep apnea) and medication non-adherence before adding further agents 4

Common Pitfalls to Avoid

• Do not use Entresto for hypertension management alone—it lacks FDA approval and guideline support for this indication, and exposes patients to unnecessary costs and risks 1, 2, 3
• Do not combine benazepril with an ARB (including the valsartan component of Entresto) as dual RAS blockade increases adverse events without benefit 4
• Do not skip the 36-hour washout if switching to Entresto for HFrEF, as concurrent ACE inhibitor use dramatically increases angioedema risk 1
• Do not add beta-blockers as third-line agents for uncomplicated hypertension unless there are compelling indications (post-MI, HFrEF, angina, rate control) 4

Special Populations

For Black patients with hypertension:

• Prefer calcium channel blocker + thiazide diuretic combination over ACE inhibitor/ARB-based regimens, as this provides superior blood pressure control in this population 4

For patients with chronic kidney disease:

• ACE inhibitors like benazepril remain first-line due to albuminuria reduction benefits; add calcium channel blockers and diuretics as needed 4