Should we use sacubitril and valsartan in this patient?

Sacubitril/Valsartan in Patient Management

Sacubitril/valsartan should be used in this patient if they have heart failure with reduced ejection fraction (HFrEF) with LVEF ≤40%, as it significantly reduces cardiovascular mortality and heart failure hospitalizations compared to ACE inhibitors alone. 1

Indications for Sacubitril/Valsartan

Sacubitril/valsartan (ARNI) is indicated in the following scenarios:

• Heart Failure with Reduced Ejection Fraction (HFrEF):

  • For patients with LVEF ≤40% and NYHA class II-IV symptoms 1
  • As first-line therapy in place of ACE inhibitors or ARBs 1, 2
  • For patients already on ACE inhibitors or ARBs who can be switched to ARNI 1

• Specific Patient Populations:

  • Particularly beneficial in patients with LVEF below 57% 1
  • Shows greater benefit in women compared to men 1
  • Can be initiated de novo in hospitalized patients with acute HFrEF before discharge 1

Contraindications and Cautions

Sacubitril/valsartan should NOT be used in patients with:

• History of angioedema related to previous ACE inhibitor or ARB therapy 3
• Concomitant use of ACE inhibitors (must wait 36 hours between switching) 3
• Concomitant use of aliskiren in patients with diabetes 3
• Severe hepatic impairment (Child-Pugh C) 3
• Pregnancy (can cause fetal harm) 3

Use with caution in:

• Patients with low blood pressure (SBP <100 mmHg) 1
• Patients with severe renal impairment (eGFR <30 mL/min/1.73m²) - use half the starting dose 3
• Moderate hepatic impairment (Child-Pugh B) - use half the starting dose 3
• Elderly patients (no dose adjustment needed, but monitor closely) 3

Dosing and Administration

• Starting dose:

  • Standard: 49/51 mg twice daily
  • For patients not currently taking ACE inhibitors or ARBs: 24/26 mg twice daily 3
  • For patients with severe renal impairment or moderate hepatic impairment: 24/26 mg twice daily 3
  • For patients with low blood pressure: 24/26 mg twice daily 1

• Target dose: 97/103 mg twice daily 2

• Uptitration strategy:

  • Increase dose every 2-4 weeks as tolerated 2
  • Monitor blood pressure, renal function, and potassium levels 1
  • If hypotension occurs, consider reducing diuretic dose first before reducing ARNI dose 3

Benefits Over ACE Inhibitors/ARBs

Sacubitril/valsartan provides several advantages over traditional ACE inhibitors or ARBs:

• 20% reduction in cardiovascular death or heart failure hospitalization compared to enalapril 1
• Improved cardiac remodeling with greater reductions in:
  • Left atrial volume 4
  • Left ventricular end-systolic and end-diastolic volumes 4
  • Mitral E/e' ratio (improved diastolic function) 4
• Superior reduction in interstitial fibrosis compared to valsartan alone, even with similar blood pressure control 5
• May decrease myocardial ischemia through reduced LV wall stress and improved coronary circulation 1

Management of Potential Side Effects

1. Hypotension:

   • Most common side effect, more frequent than with ACE inhibitors 6
   • Correct volume/salt depletion before starting therapy 3
   • Consider reducing diuretic dose if symptomatic hypotension occurs 1
   • If persistent, temporarily reduce dose or discontinue 3

2. Angioedema:

   • Incidence similar to ACE inhibitors 1
   • Higher risk in Black patients 3
   • Discontinue immediately if it occurs and provide appropriate therapy 3

3. Renal dysfunction:

   • Monitor serum creatinine 3
   • Down-titrate or interrupt therapy if clinically significant decrease in renal function occurs 3

4. Hyperkalemia:

   • Monitor serum potassium periodically 3
   • Higher risk in patients with severe renal impairment, diabetes, or high potassium diet 3

Special Considerations

• Elderly patients: No dose adjustment needed, but monitor more closely for hypotension 1, 3
• Chronic coronary syndrome: May provide additional benefit in reducing coronary events compared to ACE inhibitors 1
• Hypertensive heart disease: Provides greater reduction in interstitial fibrosis and LV mass compared to valsartan alone 5
• Switching from ACE inhibitors: Allow at least 36 hours between last ACE inhibitor dose and first ARNI dose to minimize angioedema risk 1, 3

Monitoring Parameters

• Blood pressure (watch for symptomatic hypotension)
• Renal function (serum creatinine)
• Serum potassium
• Clinical signs and symptoms of heart failure
• NT-proBNP levels (if available)

In conclusion, sacubitril/valsartan represents a significant advancement in heart failure therapy and should be considered for patients with HFrEF to improve mortality and morbidity outcomes, with appropriate monitoring for potential side effects.