See the DrugPatentWatch profile for entresto
What Studies Show on Entresto vs. Enalapril
The PARADIGM-HF trial, a head-to-head study of over 8,400 patients with heart failure with reduced ejection fraction (HFrEF), found Entresto (sacubitril/valsartan) reduced cardiovascular death or heart failure hospitalization by 20% compared to enalapril. Entresto lowered all-cause mortality by 16% and heart failure hospitalizations by 21%. Benefits appeared within weeks and grew over the 27-month median follow-up.[1][2]
How Do They Work and Why the Difference?
Enalapril, an ACE inhibitor, blocks angiotensin II to ease heart strain. Entresto combines a neprilysin inhibitor (which boosts protective peptides like natriuretic peptides) with an ARB, providing dual vasodilation and neurohormonal benefits. This mechanism drives Entresto's edge in reducing death and hospitalizations, especially in NYHA class II-IV HFrEF patients.[1][3]
Who Benefits Most from Entresto Over Enalapril?
Entresto showed strongest results in patients with ejection fraction ≤40%, higher baseline BNP levels, or prior heart failure events. Subgroups like those ≥65 years old or with kidney impairment still gained benefit, though monitoring is needed for hyperkalemia or angioedema risks.[1][2]
What About Other Trials or Long-Term Data?
PARADIGM-HF remains the landmark trial; smaller studies and real-world data (e.g., from registries) confirm similar outcomes, with Entresto reducing readmissions by 15-25%. No large trials contradict this for HFrEF. For heart failure with preserved ejection fraction (HFpEF), evidence is weaker—PARAGON-HF showed modest benefits not reaching statistical significance overall.[2][4]
Side Effects and Practical Differences
Entresto causes more hypotension (14% vs. 9.2%) and elevated potassium but less cough (not seen with enalapril's 12%). Discontinuation rates were similar (10.7% vs. 12.3%). Enalapril is cheaper as a generic; Entresto costs more but guidelines now prefer it as first-line for HFrEF.[1][5]
Current Guidelines and When to Switch
ACC/AHA and ESC guidelines recommend Entresto over ACE inhibitors like enalapril for symptomatic HFrEF (Class I, Level A evidence). Switch if tolerated on enalapril; start directly on Entresto in new cases.[5]
[1]: NEJM - PARADIGM-HF Trial (2014)
[2]: FDA Label - Entresto
[3]: Circulation - Mechanism Review (2016)
[4]: NEJM - PARAGON-HF (2019)
[5]: ACC/AHA HF Guideline (2022)