At what point of serum creatinine elevation or hypotension should we hold or discontinue Angiotensin Receptor-Neprilysin Inhibitor (ARNI) therapy?

When to Hold or Discontinue ARNI Therapy Based on Serum Creatinine Elevation or Hypotension

ARNI therapy should be held if serum creatinine rises by more than 30% from baseline within 4 weeks of initiation or dose increase, and discontinued if creatinine rises to 310 μmol/L (3.5 mg/dL) or above. For hypotension, ARNI should be reduced or discontinued only if the patient experiences symptomatic hypotension that persists despite adjustment of other medications 1.

Renal Function Monitoring and Management

Creatinine Thresholds

• Initial rise: Some increase in serum creatinine is expected and acceptable after starting ARNI therapy
• Acceptable increase: Up to 30% rise from baseline 1
• Action thresholds:
  • If creatinine rises >30% within 4 weeks: Hold ARNI and investigate causes 1
  • If creatinine rises above 265 μmol/L (3.0 mg/dL) but below 310 μmol/L (3.5 mg/dL): Reduce ARNI dose by half and monitor closely 1
  • If creatinine rises to or above 310 μmol/L (3.5 mg/dL): Stop ARNI immediately 1

Monitoring Schedule

• Check renal function and electrolytes before starting ARNI
• Recheck within 1-2 weeks after initiation or dose increase 1
• After stabilization: Monitor at 1,3, and 6 months, then periodically thereafter 1

Hypotension Management

Blood Pressure Thresholds

• Asymptomatic hypotension: No intervention required 1
• Symptomatic hypotension (dizziness, lightheadedness):
  • First approach: Reduce diuretics and other hypotensive agents (except beta-blockers) 1
  • If symptoms persist despite adjustments: Consider reducing ARNI dose 1
  • If severe symptoms continue: Temporarily discontinue ARNI 1

Management Steps for Hypotension

1. Assess for and correct volume depletion
2. Review and adjust concurrent medications
3. Reduce diuretic dose if appropriate
4. If symptoms persist, reduce ARNI dose
5. If severe symptoms continue despite interventions, discontinue ARNI

Hyperkalemia Management

While not specifically mentioned in your question, hyperkalemia is an important consideration:

• If potassium rises above 5.5 mmol/L: Halve ARNI dose and monitor closely 1
• If potassium rises above 6.0 mmol/L: Stop ARNI immediately 1
• Before dose reduction, consider:
  • Reviewing concurrent medications causing hyperkalemia
  • Moderating potassium intake
  • Using diuretics or gastrointestinal cation exchangers 1

Special Considerations

Advanced CKD

• ARNI can be used with careful monitoring even in advanced CKD (eGFR <30 mL/min/1.73m²) 2
• More frequent monitoring is required in these patients
• Consider lower starting doses and slower titration

Common Pitfalls to Avoid

• Don't discontinue too quickly: Some rise in creatinine is expected and not clinically significant unless rapid and substantial 1
• Don't ignore other causes: Check for nephrotoxic drugs (especially NSAIDs), dehydration, or worsening heart failure 1
• Don't fail to monitor: Regular monitoring of renal function and electrolytes is essential, especially after initiation or dose changes 1
• Don't overlook volume status: Overly aggressive diuresis can precipitate renal dysfunction in patients on ARNI 1

Restarting ARNI After Holding

• Once the precipitating factor is addressed and renal function improves, consider restarting at a lower dose
• Resume careful monitoring after restarting
• Aim to achieve the highest tolerated dose for optimal cardiovascular benefit 1

Remember that ARNI therapy provides significant mortality and morbidity benefits for heart failure patients, so the goal should be to maintain therapy at the highest tolerated dose whenever possible while ensuring patient safety through appropriate monitoring and management of adverse effects.