Summary

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• Entresto (sacubitril and valsartan) is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure, with benefits most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. It is also indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. Entresto reduces NT-proBNP and is expected to improve cardiovascular outcomes.
• This summary is based on the review of 30 systematic review(s)/meta-analysis(es). ^[1-30]
• HFrEF (Heart Failure with Reduced Ejection Fraction): Sacubitril/valsartan significantly reduced all-cause mortality (RR 0.70, 95% CI 0.53-0.93) and heart failure hospitalizations (RR 0.62; 95% CI, 0.48-0.80) compared to ACE inhibitors (ACEi) and ARBs.
• HFpEF (Heart Failure with Preserved Ejection Fraction) and HFmrEF (Mildly Reduced Ejection Fraction): Sacubitril/valsartan showed no significant reduction in cardiovascular death or all-cause mortality but did reduce heart failure hospitalizations (RR 0.78; 95% CI, 0.65-0.85).
• Comparison with SGLT2 Inhibitors: Sacubitril/valsartan demonstrated a larger hazard rate reduction in composite outcomes and cardiovascular death compared to SGLT2 inhibitors.
• Cost-Effectiveness: Sacubitril/valsartan was generally cost-effective in chronic HFrEF patients.
• Sacubitril/valsartan was associated with a higher incidence of hypotension compared to ACEi/ARB and valsartan (OR 1.67, 95% CI 1.27 to 2.19).
• There was no significant increase in hyperkalemia or worsening renal function compared to ACEi/ARB.
• In older adults and patients with chronic kidney disease (CKD), sacubitril/valsartan demonstrated better renal outcomes, with a significant reduction in severe hyperkalemia and drug discontinuation due to renal events.