What is the recommended dosage of sacubitril/valsartan (Angiotensin Receptor-Neprilysin Inhibitor) for a 71-year-old patient with Impaired renal function?

Sacubitril/Valsartan Dosing for a 71-Year-Old Patient with Impaired Renal Function

For a 71-year-old patient with impaired renal function, sacubitril/valsartan should be started at a reduced dose of 24/26 mg twice daily and titrated gradually to the target dose of 97/103 mg twice daily as tolerated. 1

Initial Dosing Considerations

When initiating sacubitril/valsartan in elderly patients with impaired renal function, several factors must be considered:

• Age-related considerations: Patients ≥75 years require more frequent monitoring of renal function, but a 71-year-old patient doesn't automatically require dose reduction based on age alone 2

• Renal impairment severity:

  • For severe renal impairment (eGFR <30 mL/min/1.73 m²): Start at half the usual dose (24/26 mg twice daily) 1
  • For mild to moderate renal impairment: No initial dose adjustment is needed, but closer monitoring is recommended 1

• Previous ACEi/ARB therapy:

  • If switching from an ARB: No washout period required 2
  • If switching from an ACEi: 36-hour washout period required to avoid angioedema 2
  • If patient was on low doses of ACEi/ARB: Start at half the usual dose 1

Titration Protocol

For a 71-year-old patient with impaired renal function:

1. Initial dose: Start with 24/26 mg twice daily 1
2. Titration schedule: Increase dose every 2-4 weeks as tolerated 1
3. Target dose: Aim for 97/103 mg twice daily if tolerated 2
4. Monitoring: Check blood pressure, renal function, and potassium levels within 1-2 weeks after starting or increasing the dose 2

Special Considerations for Impaired Renal Function

• Severe renal impairment (eGFR <30 mL/min/1.73 m²):

  • Recent evidence suggests sacubitril/valsartan can be continued even when eGFR declines below 30 mL/min/1.73 m² 3
  • The UK HARP-III trial showed that sacubitril/valsartan had similar effects on kidney function compared to irbesartan in patients with CKD, while providing additional benefits of lowering blood pressure and cardiac biomarkers 4

• Pharmacokinetic changes:

  • Sacubitrilat (active metabolite) exposure increases 2.1-2.7 fold in renal impairment 5
  • Half-life increases from 12 hours to 21-38.5 hours depending on severity of renal impairment 5

Monitoring Recommendations

For this 71-year-old patient with impaired renal function:

• Initial monitoring: Check renal function, potassium, and blood pressure within 1-2 weeks after starting therapy 2
• Follow-up monitoring: More frequent monitoring is needed compared to patients with normal renal function 2
• Parameters to monitor:
  • Blood pressure (watch for symptomatic hypotension)
  • Renal function (eGFR)
  • Serum potassium levels
  • Clinical symptoms (dizziness, fatigue)

Management of Adverse Effects

• If symptomatic hypotension occurs (systolic BP <100 mmHg):

  • Consider temporarily holding the medication
  • When restarting, use a lower dose (24/26 mg twice daily) 2
  • Ensure patient is not volume-depleted 2

• If renal function worsens:

  • Moderate eGFR decline (>15%) when transitioning to sacubitril/valsartan is not consistently associated with adverse outcomes 6
  • The benefits of sacubitril/valsartan are maintained despite early eGFR changes 6
  • Early eGFR changes should not deter continuation or uptitration 6

Clinical Pearls

• Sacubitril/valsartan has been shown to be safe in CKD patients, with stability in CKD progression after 6 months 7

• When low blood pressure is a concern, consider starting with the lowest dose and titrating slowly with small increments 8

• For patients with heart failure and reduced ejection fraction who have low blood pressure, consider starting SGLT2i and MRA first (as they don't lower BP significantly), then add sacubitril/valsartan at low dose 8

• The benefits of sacubitril/valsartan on mortality and morbidity are significant enough that maintaining patients on therapy with appropriate dose adjustments is preferred over discontinuation 2