Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.
Study design: Multicenter, randomized, double-blind, active-controlled trial.
Setting: A total of 129 centers in the United States.
Synopsis: Of 881 patients with acute HFrEF, 440 were randomized to receive sacubitril/valsartan and 441 were randomized to receive enalapril. The majority of patients were men; mean age was 61 years. The primary outcome was the mean reduction in NT-proBNP concentration at weeks 4 and 8 as compared with baseline. In the sacubitril/valsartan group, there was a 46.7% reduction from baseline, and in the enalapril group, there was a 25.3% reduction from baseline. With regard to drug safety, there was no difference between groups in worsening renal function, symptomatic hypotension, or hyperkalemia.
A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.
Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.
Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.
Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.