What is the best course of action for a patient with hypertension who is currently taking Entresto (sacubitril/valsartan)?

Management of Hypertension in a Patient on Entresto

Add a dihydropyridine calcium channel blocker (e.g., amlodipine) as first-line therapy for uncontrolled hypertension in patients already taking Entresto. 1

Understanding the Clinical Context

Entresto (sacubitril/valsartan) already contains an ARB component (valsartan), which means the patient is receiving renin-angiotensin system blockade as part of their heart failure therapy 2. Since you cannot add another ACE inhibitor or ARB (contraindicated with Entresto), and the patient already has RAS blockade covered, the next logical step follows standard hypertension algorithms but excludes RAS blockers 3.

Blood Pressure Targets

• Target BP <130/80 mmHg but maintain >120/70 mmHg to avoid symptomatic hypotension, which is a known risk with Entresto 1, 3
• For elderly patients (≥85 years) or those with frailty, less aggressive targets may be appropriate 1
• Confirm elevated BP with out-of-office measurements (home BP monitoring or ambulatory BP monitoring) before intensifying therapy 1

Stepwise Medication Algorithm

Step 1: Add Dihydropyridine Calcium Channel Blocker

• Amlodipine, nifedipine, or other DHP-CCB is the preferred first addition 4, 1
• This combination (Entresto + CCB) is explicitly recommended by the 2024 ESC guidelines 4

Step 2: Add Thiazide or Thiazide-Like Diuretic

• If BP remains uncontrolled on Entresto + CCB, add chlorthalidone or indapamide 4, 1
• Use loop diuretics instead if eGFR <30 ml/min/1.73m² 1
• Thiazide-like diuretics (chlorthalidone, indapamide) are preferred over hydrochlorothiazide 4

Step 3: Consider Spironolactone for Resistant Hypertension

• If BP remains >140/90 mmHg on Entresto + CCB + diuretic, add spironolactone 25-50 mg daily 4, 5
• Only use if serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 4
• Alternatives if spironolactone contraindicated: eplerenone (50-200 mg, may need twice daily dosing), amiloride, doxazosin, or beta-blockers 4, 5

Step 4: Beta-Blockers (If Compelling Indication)

• Add beta-blockers if patient has coronary artery disease, post-MI, or needs heart rate control 4, 1
• Prefer vasodilating beta-blockers (carvedilol, nebivolol, labetalol) over traditional agents 4

Critical Safety Monitoring

Hypotension Management

• Entresto commonly causes hypotension; monitor closely especially when adding additional BP medications 3, 6
• If symptomatic hypotension occurs: reduce diuretic dose first, then consider dose adjustment of other antihypertensives 3
• Do not discontinue Entresto unless absolutely necessary, as it provides mortality benefit in heart failure 1

Renal Function and Electrolytes

• Monitor serum creatinine and potassium closely, especially when adding spironolactone 3
• Expect modest increases in creatinine; down-titrate medications if clinically significant decline in renal function occurs 3
• Risk of hyperkalemia increases with combination of Entresto + spironolactone + reduced renal function 3

Angioedema Risk

• Black patients have higher angioedema risk with Entresto; counsel patients on symptoms 3
• If angioedema occurs, discontinue Entresto immediately and do not rechallenge 3

Common Pitfalls to Avoid

• Never add an ACE inhibitor to Entresto - contraindicated due to increased angioedema risk; must wait 36 hours between switching 3
• Never add another ARB to Entresto - dual RAS blockade is not recommended 4
• Do not use aliskiren with Entresto in diabetic patients - contraindicated 3
• Avoid aggressive diuresis that causes volume depletion - increases hypotension risk with Entresto 3
• Do not assume BP control without out-of-office measurements - white coat effect is common 1

Lifestyle Modifications

• Sodium restriction (<2 g/day), weight loss if overweight, regular aerobic exercise, and alcohol moderation are essential adjuncts 1
• These interventions may reduce medication burden and improve BP control 1

When to Refer

• Refer to hypertension specialist if BP remains uncontrolled on triple therapy (Entresto + CCB + diuretic) after confirming adherence and excluding secondary causes 4
• Consider screening for secondary hypertension if resistant pattern emerges, particularly primary aldosteronism, renal artery stenosis, or sleep apnea 4