How to manage bradycardia in a patient with heart failure, impaired renal function, and atrial fibrillation on Entresto (sacubitril/valsartan) and metoprolol?

Management of Bradycardia in Heart Failure with Entresto and Metoprolol

Reduce the metoprolol dose by 50% (to 12.5 mg twice daily) rather than discontinuing it, while maintaining the current Entresto dose, and closely monitor for symptom improvement over 1-2 weeks. 1

Immediate Assessment

Before making medication adjustments, confirm the bradycardia is truly problematic:

• Assess for symptoms of poor perfusion: acute altered mental status, dizziness, lightheadedness, syncope, worsening dyspnea, or signs of shock 2
• Obtain a 12-lead ECG to identify the specific bradyarrhythmia (sinus bradycardia vs. AV block) and rule out second or third-degree heart block 3, 2
• Check blood pressure: symptomatic hypotension (systolic <100 mmHg with symptoms) requires more aggressive intervention 1
• Rule out other reversible causes: hypothyroidism, infection, electrolyte abnormalities, or medication interactions 1

The key distinction is whether the bradycardia is symptomatic or asymptomatic. Asymptomatic bradycardia alone may not require intervention if the patient is otherwise stable 2.

Medication Management Strategy

Why Reduce Metoprolol First (Not Entresto)

Beta-blocker dose reduction is the appropriate first step for several critical reasons:

• Metoprolol is the primary culprit for bradycardia, not Entresto 3, 1
• Entresto provides renal protection in this patient with CrCl 29 ml/min, with studies showing it slows eGFR decline more effectively than ARBs alone and may even improve renal function 4, 5, 6
• Maintaining beta-blockade at some level is crucial: complete discontinuation increases mortality risk 2.7-fold compared to continuous use 1
• Abrupt beta-blocker withdrawal is dangerous: it can cause severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias, with a 50% mortality rate reported in one study 1, 7

Specific Dosing Recommendations

Reduce metoprolol from 25 mg twice daily to 12.5 mg twice daily 1:

• This 50% dose reduction maintains some beta-blockade benefit while addressing the bradycardia 3, 1
• For heart rate <50 bpm with worsening symptoms, halve the beta-blocker dose 3
• ACC/AHA perioperative guidelines specify holding beta-blockers when heart rate is consistently below 45 bpm 1

Keep Entresto at 25 mg twice daily (already appropriately dose-reduced for renal function):

• The dose reduction from 50 mg to 25 mg twice daily was appropriate given CrCl 29 ml/min 5
• Entresto has shown significant improvements in eGFR in patients with renal dysfunction (mean increase 4.1 ml/min/1.73 m²) 5
• Long-term Entresto therapy provides renal protection and improved outcomes in HFrEF patients, with effects maintained even in CKD 6

Atrial Fibrillation Considerations

This patient's atrial fibrillation adds complexity but doesn't change the fundamental approach:

• Rate control targets: aim for resting heart rate 50-60 bpm unless limiting side effects occur 1
• Current heart rate <60 bpm is at the lower acceptable limit for AF rate control 1
• Consider that some bradycardia may be acceptable in AF if the patient is asymptomatic and adequately rate-controlled 2

Monitoring Protocol

After reducing metoprolol to 12.5 mg twice daily:

• Monitor heart rate, blood pressure, and symptoms within 1-2 weeks 3, 1
• Watch specifically for:
  • Symptomatic bradycardia (HR <60 bpm with dizziness or lightheadedness) 1
  • Hypotension (systolic BP <100 mmHg with symptoms) 1
  • Worsening heart failure symptoms (increased dyspnea, fatigue, edema, weight gain) 3
• Check renal function and potassium given the combination of Entresto and reduced renal function 5

When to Hold Metoprolol Completely

Temporarily hold metoprolol only if 1:

• Heart rate consistently <45 bpm 1
• Systolic blood pressure <100 mmHg with symptoms of hypoperfusion 1
• Severe symptomatic bradycardia with dizziness, syncope, or near-syncope 1
• Development of second or third-degree heart block 3, 7

Alternative Considerations if Bradycardia Persists

If bradycardia remains problematic after metoprolol dose reduction:

• Review other rate-lowering medications: digoxin, amiodarone, or any other drugs that may contribute 3, 2
• Consider switching beta-blockers: carvedilol has additional alpha-blocking effects that may worsen bradycardia; metoprolol or bisoprolol may be better tolerated 2
• Evaluate for device therapy: if the patient has QRS >120 ms or LVEF <35%, cardiac resynchronization therapy (CRT) may allow optimization of medical therapy by eliminating drug-induced bradycardia as a limiting factor 2

Critical Pitfalls to Avoid

• Never abruptly discontinue metoprolol without tapering, especially in patients with potential coronary artery disease 1, 7
• Don't assume all bradycardia requires intervention: asymptomatic bradycardia with adequate perfusion may be acceptable 2
• Don't reduce Entresto first: it provides crucial renal protection in this patient with impaired kidney function 4, 5, 6
• Don't forget to assess for reversible causes before attributing bradycardia solely to medications 1

Expected Outcomes

With appropriate metoprolol dose reduction:

• Heart rate should improve within days to 1-2 weeks 3
• Beta-blocker benefits are maintained even at lower doses: some beta-blocker is better than no beta-blocker 3
• Renal function should remain stable or improve with continued Entresto therapy 5, 6
• If symptoms don't improve, seek specialist cardiology consultation 3