LCZ696 versus Enalapril in Heart Failure. The New England Journal of Medicine. 2014.

Clinical Question

Does the angiotensin receptor–neprilysin inhibitor LCZ696 confer a survival benefit over enalapril in patients with heart failure and a reduced ejection fraction?

Bottom Line

LCZ696, compared to enalapril, reduced the risks of cardiovascular death and hospitalization for heart failure in patients with heart failure and reduced ejection fraction.

Major Points

Guidelines

As of the knowledge cutoff date, LCZ696 (sacubitril/valsartan) may be considered in place of ACE inhibitors to further reduce the risks of morbidity and mortality in patients with heart failure with reduced ejection fraction.

Design

Multicenter, double-blind, parallel-group, randomized, controlled trial.

Population

8,442 patients with NYHA class II, III, or IV heart failure and an ejection fraction of ≤40%.

Interventions

Patients were randomized to LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy.

Outcomes

The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, with the trial designed to detect a difference in rates of death from cardiovascular causes.

Major Points

- LCZ696 group saw a primary outcome event in 21.8% vs. 26.5% in the enalapril group (HR 0.80; 95% CI, 0.73 to 0.87; P<0.001).
- Death from cardiovascular causes occurred in 17.0% on LCZ696 vs. 19.8% on enalapril (HR 0.84; 95% CI, 0.76 to 0.93; P<0.001).
- Hospitalization for heart failure was also 21% lower in the LCZ696 group (P<0.001).
- Improved symptoms and physical limitations associated with heart failure in the LCZ696 group (P=0.001).

Criticisms

While LCZ696 had higher rates of hypotension and nonserious angioedema, it had lower rates of renal impairment, hyperkalemia, and cough compared to the enalapril group.

Funding

The study was funded by Novartis.

Further Reading

The full text article was published in The New England Journal of Medicine, 2014, and is available at NEJM.org.