Early in-hospital initiation of ARNI after ADHF improves outcomes in HFrEF

Initiation of Angiotensin-Neprilysin Inhibition after Acute Decompensated Heart Failure: Results of the Open-Label Extension of the PIONEER-HF Trial

Presented at ACC.19 by Adam D. DeVore (Durham, NC, USA)

Introduction and methods

Data of the PIONEER-HF trial showed significantly reduced NT-proBNP levels and improved clinical outcomes after 8 weeks in patients stabilized after acute decompensated heart failure (ADHF) who were randomized to in-hospital initiation of sacubitril/valsartan (S/V), compared to those randomized to enalapril. Few data are available on the impact of post-discharge initiation of S/V after ADHF. PIONEER-HF was a multicenter, double-blind, randomized trial including 881 patients with ADHF, ejection fraction ≤40% (HFrEF), increased natriuretic peptides, and hemodynamic stability. Participants were randomized 1:1 to receive either in-hospital initiation of S/V (n=440) or enalapril (n=441).

After 8 weeks in the PIONEER-HF trial, participants continued in a 4-week, open-label study with all patients receiving S/V (n=832). This extension study examined changes in NT-proBNP levels among patients with heart failure and reduced ejection fraction (HFrEF) who were hospitalized for ADHF and were switched from enalapril to S/V after 8 weeks, and compared the totality of clinical events during the 12-week study period by randomized treatment arms.

Main results

• From week 8 to 12, NT-proBNP levels were more reduced in those who switched from enalapril to S/V (-35.8%, 95%CI: -30.6 to -40.7), compared to those who continued S/V (-18.5%, 95%CI: -11.8 to -24.7) (P<0.0001).
• In those who received early initiation of S/V, reduced death, HF hospitalization or LVAD implantation was observed (HR: 0.67, 95%CI: 0.48-0.94, P=0.020), compared to those who received in-hospital initiation of enalapril and were switched to S/V after 8 weeks.
• There was no significant difference in worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema events between the 2 groups.

Conclusion

This extension study of the PIONEER-HF trial in patients with HFrEF who were recently hospitalized for ADHF showed a higher reduction of NT-proBNP levels in those with early initiation of enalapril and who were post-discharge transitioned to S/V at 8 weeks, compared to those who continued S/V treatment. In-hospital initiation of S/V improved clinical outcomes at 12 weeks, compared to in-hospital initiation of enalapril followed by S/V. The early improvement in post-discharge outcomes supports the in-hospital initiation of S/V in stabilized HFrEF patients with ADHF.

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