What are the considerations before starting someone on Entresto (sacubitril/valsartan) for hypertension?

Considerations Before Starting Entresto for Hypertension

Entresto (sacubitril/valsartan) is not FDA-approved or recommended as a first-line agent for hypertension alone, and should primarily be reserved for patients with heart failure with reduced ejection fraction (HFrEF) who may also have hypertension. 1

Primary Indications and Contraindications

Entresto is primarily indicated for:

• Heart failure with reduced ejection fraction (HFrEF) to reduce cardiovascular mortality and hospitalization 2
• Not a first-line agent for hypertension without heart failure

Absolute contraindications include:

• Hypersensitivity to any component of the medication
• History of angioedema related to previous ACE inhibitor or ARB therapy
• Concomitant use of ACE inhibitors (requires 36-hour washout period)
• Concomitant use of aliskiren in patients with diabetes
• Pregnancy (due to fetal toxicity) 1

Pre-Initiation Assessment

Blood Pressure Evaluation

• Confirm baseline blood pressure and assess for hypotension risk (SBP <100 mmHg)
• Patients with activated renin-angiotensin system (volume/salt-depleted) are at higher risk for hypotension 1
• Correct volume or salt depletion prior to administration 1

Renal Function Assessment

• Check baseline renal function (eGFR)
• For severe renal impairment (eGFR <30 mL/min/1.73m²), start at half the recommended dose 1
• Monitor renal function closely, especially in patients with bilateral or unilateral renal artery stenosis 1

Electrolyte Monitoring

• Check baseline potassium levels
• Higher risk of hyperkalemia in patients with:
  • Severe renal impairment
  • Diabetes
  • Hypoaldosteronism
  • High potassium diet 1

Dosing Considerations

Transitioning from Current Therapy

• When switching from ACE inhibitor to Entresto:
  • Mandatory 36-hour washout period to avoid angioedema 2, 1
• When switching from ARB to Entresto:
  • No washout period required 2

Initial Dosing

• For hypertensive patients with HFrEF:
  • If previously on high-dose ACEI/ARB: Start at 49/51 mg twice daily
  • If previously on low/medium-dose ACEI/ARB: Start at 24/26 mg twice daily
  • If ACEI/ARB naïve, severe renal impairment, moderate hepatic impairment, or elderly (≥75 years): Start at 24/26 mg twice daily 2

Titration Strategy

• Gradual titration approach maximizes attainment of target dose
• Up-titrate every 2-4 weeks as tolerated 2
• Target maintenance dose: 97/103 mg twice daily 1

Monitoring After Initiation

Short-term Monitoring

• Blood pressure: Watch for symptomatic hypotension
• Renal function: Monitor for decline in renal function
• Potassium: Watch for hyperkalemia
• Angioedema: Higher risk in Black patients and those with prior history 1

Management of Side Effects

• If hypotension occurs:
  • Consider dose adjustment of diuretics
  • Adjust concomitant antihypertensive drugs
  • Treat other causes of hypotension (e.g., hypovolemia)
  • If persistent, reduce dosage or temporarily discontinue 1
• If hyperkalemia occurs:
  • Treat appropriately
  • Consider dose reduction or interruption 1

Special Population Considerations

• Black patients: Higher risk of angioedema 1
• Elderly patients (≥75 years): Start at lower dose 2
• Patients with heart failure: May benefit from empiric modest lowering of loop diuretic dose to mitigate hypotensive effects 2
• Patients with borderline BP (≤100 mmHg): Careful administration and follow-up advised 2

Practical Tips

• For patients with borderline blood pressure, consider reducing diuretic dose in non-congested patients to mitigate hypotensive effects 2
• In patients with heart failure, Entresto may exert a more notable effect on blood pressure compared to ACEIs/ARBs 2
• Achievement of target doses may be modest in clinical practice due to side effects and patient compliance 3

While there is some emerging evidence for Entresto's potential benefits in hypertension 4, 5, 6, current guidelines do not recommend it as a primary antihypertensive agent in the absence of heart failure with reduced ejection fraction.