BACKGROUND: -Clinical trials in heart failure have focused on the improvement in symptoms
or decreases in the risk of death and other cardiovascular events. Little is known
about the effect of drugs on the risk of clinical deterioration in surviving patients.
METHODS AND RESULTS: -We compared the angiotensin-neprilysin inhibitor LCZ696 (400
mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily)
in 8399 patients with heart failure and reduced ejection fraction in a double-blind
trial. The analyses focused on prespecified measures of nonfatal clinical deterioration.
In comparison with the enalapril group, fewer LCZ696-treated patients required intensification
of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence
interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart
failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients
in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851
versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879;
18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31%
risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac
transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization
with LCZ696 was evident within the first 30 days after randomization. Worsening of
symptom scores in surviving patients was consistently more common in the enalapril
group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial
wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus
enalapril. CONCLUSIONS: -Angiotensin-neprilysin inhibition prevents the clinical progression
of surviving patients with heart failure more effectively than angiotensin-converting
enzyme inhibition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov.
Unique identifier: NCT01035255.
