- Question
- Is the angiotensin receptor-neprilysin inhibitor LCZ696 superior to enalapril in reducing death and hospitalization in patients with heart failure and reduced ejection fraction?
- Design
- Randomized, double-blind, phase 3, active-controlled trial enrolling 8442 patients. It was stopped early, per prespecified rules, for overwhelming benefit, after a median follow-up of 27 months.
- Population
- Patients with class II, III, or IV heart failure and an ejection fraction of 40% or less, receiving recommended therapy. Randomization was preceded by a run-in period on enalapril and then LCZ696.
- Intervention
- LCZ696 at 200 mg twice daily, added to recommended background therapy.
- Control
- Enalapril at 10 mg twice daily, added to recommended background therapy.
- Primary outcome
- Composite of death from cardiovascular causes or hospitalization for heart failure, although the trial was designed to detect a difference in cardiovascular death.
- Results
- The primary outcome occurred in 914 patients (21.8%) with LCZ696 and 1117 (26.5%) with enalapril (HR 0.80; 95% CI 0.73 to 0.87; P<0.001). Cardiovascular death occurred in 13.3% with LCZ696 versus 16.5% with enalapril (HR 0.80; 95% CI 0.71 to 0.89; P<0.001).
- Safety
- The LCZ696 group had higher proportions of hypotension and nonserious angioedema, and lower proportions of renal impairment, hyperkalemia, and cough than the enalapril group.
- Conclusion
- LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure.
- Why it matters
- It showed that replacing an ACE inhibitor with a combined angiotensin receptor-neprilysin inhibitor could improve clinical outcomes in heart failure with reduced ejection fraction, opening a new foundational therapeutic option.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 7, 2026