Sacubitril/Valsartan versus enalapril in nonischemic heart failure in Paradigm-Hf trial

Background: We compared the angiotensin receptor–neprilysin inhibitor LCZ696 (sacubitril/valsartan) with enalapril in patients who had nonischemic heart failure with a reduced ejection fraction. Methods: In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes.Results: The trial was stopped early, according to prespecified rules, after a median follow up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. The ischemic patients were 5036 (60%) patients and non-ischemic patients were 3363 (40%) patients. In ischemic and in non-ischemic group the LCZ696 was superior to enalapril for reduce primary outcome and CV death (P< 0.001). In LCZ696 group: the primary outcome had occurred in 339 patients (20.16 %) in the non-ischemic group and 575 patients (22.9 %) in the ischemic group (P: 0.03). A total of 199 patients (11.8%) in non-ischemic group and 359 patients in ischemic group (14.3%) died from cardiovascular causes (P: 0.01). and no significant difference between in CV death and primary outcome in enalapril group in the ischemic and non-ischemic patientsConclusions: LCZ696 was superior to enalapril in reducing the risks of cardiovascular death and hospitalization for heart failure in ischemic and non-ischemic heart failure.