What is the treatment regimen for congestive heart failure (CHF) using sacubitril valsartan?

Sacubitril/Valsartan Treatment Regimen for Congestive Heart Failure

Sacubitril/valsartan is indicated to reduce the risk of cardiovascular death and hospitalization in adult patients with chronic heart failure and reduced ejection fraction (HFrEF), with the recommended starting dose of 49/51 mg orally twice daily, titrated to the target maintenance dose of 97/103 mg twice daily after 2-4 weeks as tolerated. 1

Indications and Patient Selection

• Sacubitril/valsartan is recommended as a replacement for ACE inhibitors or ARBs in patients with symptomatic HFrEF to reduce morbidity and mortality 2, 3
• It is primarily indicated for patients with chronic heart failure with reduced ejection fraction (LVEF is a variable measure, so clinical judgment should guide patient selection) 1
• Sacubitril/valsartan provides superior reduction in cardiovascular death and HF hospitalization compared to ACE inhibitors 3, 4

Dosing Protocol

• Initial Dosing:

  • The recommended starting dose is 49/51 mg orally twice daily 1
  • For patients with severe renal impairment (eGFR <30 mL/min/1.73m²), consider a lower starting dose 1
  • Most real-world patients initially start at the lowest dose of 24/26 mg twice daily 5

• Dose Titration:

  • Double the dose after 2-4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated 1
  • In real-world practice, only about 17% of patients achieve the target dose after 4 months of treatment 5
  • Adjust doses every 2 weeks as tolerated by the patient 1

Important Considerations Before Initiation

• A 36-hour washout period is required when switching from an ACE inhibitor to sacubitril/valsartan 1
• Direct initiation of sacubitril/valsartan without prior ACE inhibitor or ARB exposure is safe and effective 2
• Ensure patients are not volume-depleted at the time of initiation to avoid hypotension 2
• In patients with borderline blood pressure (systolic BP ≤100 mmHg), careful administration and follow-up are advised 2

Managing Potential Side Effects

• Hypotension is the most common side effect:

  • In the PARADIGM-HF trial, 16.0% of patients experienced asymptomatic hypotension, while 11.1% experienced symptomatic hypotension 2
  • In patients with borderline blood pressure, consider reducing loop diuretic doses in non-congested patients to mitigate hypotensive effects 2
  • Despite hypotension, the efficacy and safety of sacubitril/valsartan are maintained 2

• Other potential side effects include:

  • Hyperkalemia (though less common than with ACE inhibitors) 6
  • Angioedema (rare but serious) 6, 4

Special Considerations

• Hospital-based initiation:

  • Initiating sacubitril/valsartan during hospitalization for acute decompensated HF is feasible after hemodynamic stabilization 2
  • About 25% of patients may develop hypotension when treated with sacubitril/valsartan in the hospital setting 2
  • About half of patients can achieve target dose within 10 weeks after in-hospital initiation 2

• Patients with low blood pressure:

  • Benefits of sacubitril/valsartan are consistent across all baseline systolic blood pressure categories, including <110 mmHg 2
  • Patients with the lowest baseline SBP (95-110 mmHg) may experience a mild BP increase over time 2

Clinical Benefits

• Reduces cardiovascular death and hospitalization for heart failure compared to enalapril 4
• Improves symptoms and reduces hospitalizations within 4 months of treatment initiation in real-world settings 5
• Reduces prognostic biomarkers (NT-proBNP, high-sensitivity cardiac troponin T) 7
• Improves health status and reverses cardiac remodeling regardless of heart failure duration 7
• May exhibit antiarrhythmic properties and reduce the risk of ventricular arrhythmias and sudden cardiac death 8

Monitoring and Follow-up

• Close follow-up and serial assessments (blood pressure, electrolytes, and renal function) should be performed after initiation 2
• Monitor for symptomatic hypotension, especially in patients with borderline blood pressure 2
• Evaluate for improvement in symptoms, including fatigue and shortness of breath 5

Contraindications and Warnings

• Contraindicated with concomitant use of an ACE inhibitor 1
• When pregnancy is detected, discontinue sacubitril/valsartan as soon as possible 1
• Use with caution in patients with severe renal impairment 1