2014, Sacubitril-valsartan vs Enalapril in HF, NEJM.
PARADIGM-HF Trial Summary
The PARADIGM HF trial randomized 8442 patients with NYHA Class II, III or IV heart failure and a reduced ejection fraction of 40% or less to receive either 200 mg of LCZ696 (which consists of sacubitril and valsartan) or enalapril in a 1:1 ratio, in addition to standard medical therapy.
The primary outcome was a composite of cardiovascular death or heart failure hospitalization but the trial was also powered to detect a difference in cardiovascular death. For at least 4 weeks before screening, patients were required to take a stable dose of a beta-blocker and an ACE inhibitor (or ARB) equivalent to at least 10 mg of enalapril daily. The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, for an overwhelming benefit with LCZ696.
The primary outcome occurred in 21.8% of patients in the LCZ696 group and 26.5% in the enalapril group (HR: 0.80; 95%CI: 0.73 to 0.87; p<0.001). A total of 17% of patients in the LCZ696 arm and 19.8% in the enalapril arm died. (HR:0.84; 95%CI: 0.76 to 0.93; p<0.001). As compared with enalapril, LCZ696 also reduced the risk of heart failure hospitlizations by 21% and decreased the symptoms of heart failure (P<0.001).