Is it safe to prescribe Entresto (sacubitril/valsartan) to an elderly patient with heart failure, normal blood pressure, and bradycardia?

Can You Give Entresto to This Elderly Patient?

Yes, you can initiate Entresto in this elderly heart failure patient with BP 120/70 and HR 60, but you must start at the lowest dose (24/26 mg twice daily) and monitor closely for hypotension and bradycardia. 1

Dosing Strategy for This Patient

Start at 24/26 mg twice daily rather than the standard 49/51 mg starting dose. 1 The FDA label specifically recommends reducing the starting dose to half the usual dose for patients not currently taking an ACE inhibitor or ARB, or those previously on low doses of these agents. 1 This lower starting dose is particularly appropriate given:

• Baseline heart rate of 60 bpm - already at the lower end of normal, increasing risk for symptomatic bradycardia 2
• Elderly status - altered pharmacokinetics with reduced hepatic and renal clearance leading to higher drug exposure 2, 3
• Blood pressure of 120/70 - leaves limited room for the expected BP reduction with Entresto 2

Critical Monitoring Requirements

Before initiating therapy:

• Verify renal function (creatinine clearance) - if severe renal impairment (CrCl <30 mL/min), the 24/26 mg twice daily starting dose is mandatory 1
• Check serum potassium levels 2
• Obtain baseline ECG to assess for conduction abnormalities 4
• Document standing and supine blood pressure 2, 4

After initiation, monitor:

• Blood pressure (both supine and standing) to detect orthostatic hypotension, which is particularly pronounced in elderly patients 2, 4
• Heart rate and symptoms of bradycardia 2
• Renal function and serum potassium within 1-2 weeks 2, 1
• Signs of symptomatic hypotension (dizziness, lightheadedness, syncope) 1, 5

Titration Approach

Titrate slowly every 2-4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated. 1 However, in this elderly patient with borderline vital signs:

• Advance to 49/51 mg twice daily only if BP remains >110/60 mmHg and HR >55 bpm without symptoms 1
• Real-world data shows that over 63% of patients remain on the lowest dose, particularly elderly patients who are more symptomatic than trial populations 6
• The 2025 meta-analysis demonstrated that while higher doses reduce NT-proBNP more significantly, lower doses still provide clinical benefit without the same hypotension risk 7

Key Safety Considerations in the Elderly

Symptomatic hypotension is the most common adverse effect and occurs significantly more frequently with sacubitril/valsartan than with ACE inhibitors. 1, 5 Elderly patients are particularly vulnerable because:

• Age-related decreased baroreceptor response makes them less able to compensate for BP drops 2, 3
• Orthostatic hypotension risk is substantially elevated, especially if the patient is on diuretics or other vasodilators 2
• Falls risk increases dramatically with postural BP changes 2

Bradycardia is listed as a cause of worsening heart failure in elderly patients and should be monitored closely. 2 While Entresto itself doesn't directly cause bradycardia, the combination with beta-blockers (which this patient likely takes) requires vigilance.

Drug Interactions to Verify

Before prescribing, confirm the patient is NOT taking:

• ACE inhibitors - absolute contraindication; must wait 36 hours after last ACE inhibitor dose 1
• Aliskiren (if diabetic) - contraindicated 1
• Potassium-sparing diuretics - may lead to dangerous hyperkalemia 2, 1
• NSAIDs - increase renal impairment risk 2, 1

Evidence Supporting Use Despite Concerns

The PARADIGM-HF trial demonstrated superior outcomes with sacubitril/valsartan compared to enalapril, reducing cardiovascular death and heart failure hospitalization. 5 Importantly:

• The drug was generally well tolerated with no increase in life-threatening adverse events 5
• Real-world Irish data showed patients actually prescribed Entresto were older and more symptomatic than PARADIGM-HF participants, yet still benefited 6
• Angioedema incidence was low 5

The mortality and morbidity benefits outweigh the hypotension risk when appropriate precautions are taken. 5, 8 This represents a paradigm shift in heart failure management, making it a more effective replacement for ACE inhibitors or ARBs. 5

Common Pitfalls to Avoid

• Do not start at standard dose (49/51 mg) in this patient - the combination of elderly age, borderline HR, and modest BP mandates the 24/26 mg starting dose 1
• Do not assume the patient can tolerate rapid titration - elderly patients require slower advancement with careful monitoring 2
• Do not overlook standing BP measurements - supine BP alone misses orthostatic hypotension, which is the primary safety concern 2, 4
• Do not continue if symptomatic hypotension develops - temporary dose reduction or discontinuation may be necessary 1

When to Reconsider or Avoid

Absolute contraindications:

• History of angioedema with ACE inhibitors or ARBs 1
• Current ACE inhibitor use (within 36 hours) 1
• Hypersensitivity to any component 1

Relative contraindications requiring extreme caution:

• Severe hepatic impairment (use not recommended) 1
• Symptomatic hypotension at baseline 1
• Severe bradycardia (<50 bpm) or high-degree AV block 2