What is the best approach for managing hypertension in patients taking Entresto (sacubitril/valsartan)?

Management of Hypertension in Patients on Entresto (Sacubitril/Valsartan)

For patients taking Entresto (sacubitril/valsartan), blood pressure management should focus on adding a calcium channel blocker and/or diuretic when additional antihypertensive therapy is needed, while avoiding ACE inhibitors and additional ARBs. 1

Understanding Entresto's Role in Blood Pressure Control

• Entresto (sacubitril/valsartan) is an angiotensin receptor-neprilysin inhibitor (ARNI) that already contains the ARB valsartan, which provides baseline blood pressure lowering effects 2
• Entresto is primarily indicated for heart failure with reduced ejection fraction (HFrEF) but has demonstrated efficacy in blood pressure reduction in hypertensive patients 3, 4
• In some countries (China and Japan), Entresto has been approved specifically as an antihypertensive agent, though this is not the case in Europe or the USA 4

Blood Pressure Targets for Patients on Entresto

• For most adults on Entresto with hypertension, the recommended blood pressure target is 120-129 mmHg systolic, provided the treatment is well tolerated 1
• In patients with heart failure, blood pressure should be lowered if ≥140/90 mmHg and treated to a target of <130/80 mmHg but >120/70 mmHg to avoid hypotension 1
• For elderly patients (≥85 years), those with frailty, or those with orthostatic hypotension, less aggressive targets may be appropriate 1

Recommended Antihypertensive Combinations with Entresto

First-line additions when BP is not controlled on Entresto:

• Dihydropyridine calcium channel blockers (CCBs) are recommended as the preferred add-on therapy 1
• Thiazide or thiazide-like diuretics (such as chlorthalidone or indapamide) are also appropriate first-line additions 1

Second-line additions:

• If BP remains uncontrolled with Entresto plus a CCB or diuretic, adding the other agent (creating a three-drug regimen) is recommended 1
• For resistant hypertension, spironolactone should be considered as a fourth agent 1

Important Contraindications and Precautions

• Never combine Entresto with ACE inhibitors due to increased risk of angioedema; maintain a 36-hour washout period when switching between these medications 2
• Avoid combining Entresto with additional ARBs, as this provides no additional benefit and increases risk of adverse effects 1
• Monitor for hypotension, which is a common side effect of Entresto, especially when combined with other antihypertensive medications 2, 5
• Assess renal function regularly, as Entresto can affect kidney function, particularly in patients with bilateral renal artery stenosis 2
• Monitor serum potassium levels, especially when combining with potassium-sparing diuretics 2

Special Considerations for Different Patient Populations

Patients with Heart Failure:

• Entresto is specifically indicated for HFrEF and may be beneficial in HFpEF 1
• Beta-blockers may be added to the regimen for patients with compelling indications (e.g., coronary artery disease, HFrEF) 1
• In patients with low blood pressure (<100 mmHg systolic) and heart failure, prioritize Entresto over other antihypertensives and adjust diuretics to avoid symptomatic hypotension 1

Patients with Chronic Kidney Disease:

• Monitor renal function closely when using Entresto in patients with CKD 2
• Loop diuretics are preferred over thiazides if eGFR <30 ml/min/1.73m² 1
• Entresto has shown benefit in patients with HFrEF and coexisting end-stage renal disease, but requires careful monitoring 6

Elderly Patients:

• Start with lower doses and titrate more gradually in elderly patients 1
• Be vigilant for orthostatic hypotension, which is more common in this population 1

Practical Approach to Hypertension Management with Entresto

1. Confirm that blood pressure is truly elevated using out-of-office measurements when possible 1
2. Ensure optimal dosing of Entresto before adding additional agents 4
3. Implement lifestyle modifications (sodium restriction, weight management, physical activity) 1
4. If BP remains elevated:
   • Add a dihydropyridine CCB or thiazide/thiazide-like diuretic 1
   • Consider using single-pill combinations (not including Entresto) to improve adherence 1
   • Monitor for hypotension, especially when initiating new medications 2
5. If BP remains uncontrolled on a three-drug regimen (Entresto + CCB + diuretic), consider adding spironolactone 1

Common Pitfalls to Avoid

• Combining Entresto with ACE inhibitors (absolute contraindication) 2
• Adding another ARB to a regimen that already includes Entresto 1
• Failing to monitor renal function and potassium levels 2
• Overlooking the potential for symptomatic hypotension, especially in volume-depleted patients 2, 5
• Discontinuing Entresto due to mild hypotension in heart failure patients when the medication provides mortality benefit 1