What is the dose titration strategy for a patient on 24/26 mg of sacubitril/valsartan (Entresto)?

Sacubitril/Valsartan Dose Titration Strategy for Patients on 24/26 mg

For patients currently on 24/26 mg of sacubitril/valsartan (Entresto), the dose should be doubled to 49/51 mg twice daily after 2-4 weeks, followed by further uptitration to the target dose of 97/103 mg twice daily after another 2-4 weeks, as tolerated by the patient. 1

Understanding the Current Dose

• 24/26 mg twice daily is the lowest available dose of sacubitril/valsartan and is typically used as:
  • An initial starting dose for patients not previously taking an ACE inhibitor or ARB 1
  • A starting dose for patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) 1
  • A starting dose for patients with moderate hepatic impairment (Child-Pugh B) 1

Recommended Titration Algorithm

1. Current dose: 24/26 mg twice daily

   • Assess tolerability: Check blood pressure, renal function, and potassium levels 2
   • If well-tolerated, proceed with uptitration

2. First uptitration step (after 2-4 weeks on current dose)

   • Increase to 49/51 mg twice daily 1
   • Monitor for hypotension, renal dysfunction, and hyperkalemia 3

3. Second uptitration step (after 2-4 weeks on 49/51 mg)

   • Increase to target dose of 97/103 mg twice daily 1
   • Continue monitoring for adverse effects

4. Maintenance phase

   • Maintain at highest tolerated dose, preferably the target dose of 97/103 mg twice daily 2

Monitoring During Titration

• Blood pressure: Watch for symptomatic hypotension (SBP <100 mmHg) 2, 3
• Renal function: Monitor for doubling of serum creatinine or eGFR decline 2
• Electrolytes: Check for hyperkalemia (K+ ≥5.5 mmol/L) 2
• Symptoms: Assess for dizziness, especially upon standing 2

Special Considerations

• If patient experiences intolerable side effects during uptitration:

  • Consider a more conservative titration approach with smaller increments and longer intervals between dose increases 3
  • For patients who started at low doses of ACEIs/ARBs before switching, a more gradual uptitration may maximize achievement of target dose 3

• If hypotension limits uptitration:

  • Assess for volume depletion and consider reducing diuretic dose if no signs of congestion 2
  • Consider temporarily reducing or discontinuing other non-essential antihypertensive medications 2
  • Educate patients that mild dizziness upon standing may be transient and doesn't necessarily require dose reduction 2

Clinical Outcomes of Proper Titration

• Achieving the target dose of 97/103 mg twice daily is associated with:
  • Improved survival and reduced hospitalizations 2
  • Progressive improvement in exercise capacity starting during the uptitration period 4
  • Positive left ventricular reverse remodeling with increased ejection fraction 4
  • Reduction in NT-proBNP levels, indicating improved hemodynamic status 5
  • Delayed but significant reduction in sST2 levels, suggesting anti-fibrotic effects 5

Common Pitfalls to Avoid

• Failure to uptitrate: Only about 27% of patients achieve target dose within 6 months in real-world practice 6
• Premature discontinuation: 34% of patients do not have an active prescription at 6 months 6
• Inadequate monitoring: Lack of follow-up during titration may lead to unnecessary discontinuation 7
• Not recognizing early benefits: Improvements in cardiac function begin during the uptitration phase, not just after reaching target dose 4, 5

Patient Populations Requiring Special Attention

• Black patients, those with high comorbidity burden (≥8 comorbidities), and recently hospitalized patients have lower adherence rates and may need more support during titration 6
• Patients with low baseline blood pressure may still tolerate and benefit from sacubitril/valsartan, but require more careful titration 2