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Initiation of Angiotensin-Neprilysin Inhibition After Acute Decompensated Heart Failure: Secondary Analysis of the Open-label Extension of the PIONEER-HF Trial.

Authors :
DeVore AD
Braunwald E
Morrow DA
Duffy CI
Ambrosy AP
Chakraborty H
McCague K
Rocha R
Velazquez EJ
Source :
JAMA cardiology [JAMA Cardiol] 2020 Feb 01; Vol. 5 (2), pp. 202-207.
Publication Year :
2020

Abstract

Importance: In PIONEER-HF, among stabilized patients with acute decompensated heart failure (ADHF), the in-hospital initiation of sacubitril/valsartan was well tolerated and led to improved outcomes compared with enalapril. However, there are limited data comparing the strategies of in-hospital vs postdischarge initiation of sacubitril/valsartan.<br />Objective: To describe changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients recently hospitalized for ADHF and switching from taking enalapril to taking sacubitril/valsartan after discharge and compare clinical outcomes for patients randomized to receive in-hospital initiation of sacubitril/valsartan vs in-hospital initiation of enalapril who later switched to taking sacubitril/valsartan during an open-label extension phase.<br />Interventions: Sacubitril/valsartan titrated to 97/103 mg twice daily.<br />Design, Setting, and Participants: The PIONEER-HF trial was a multicenter, randomized, double-blind, active-controlled trial conducted at 129 US sites between May 2016 and May 2018 that compared the in-hospital initiation of sacubitril/valsartan vs enalapril (titrated to target dose, 10 mg twice daily) for 8 weeks among patients admitted for ADHF with reduced ejection fraction and hemodynamic stability. All patients were to continue in a 4-week, open-label study of sacubitril/valsartan; of 881 patients enrolled in PIONEER-HF, 832 (94%) continued in the open-label study.<br />Main Outcomes and Measures: Changes in NT-proBNP levels from week 8 to 12 as well as the exploratory composite of heart failure rehospitalization or cardiovascular death from randomization through week 12.<br />Results: Of 881 participants, 226 (27.7%) were women, 487 (58.5%) were white, 297 (35.7%) were black, 15 (1.8%) were Asian, and 73 (8.8%) were of Hispanic ethnicity; the mean (SD) age was 61 (14) years. For patients who continued to take sacubitril/valsartan, NT-proBNP levels declined -17.2% (95% CI, -3.2 to -29.1) from week 8 to 12. The NT-proBNP levels declined to a greater extent for those switching from taking enalapril to sacubitril/valsartan after the week 8 visit (-37.4%; 95% CI, -28.1 to -45.6; Pā€‰<ā€‰.001; comparing changes in 2 groups). Over the entire 12 weeks of follow-up, patients that began taking sacubitril/valsartan in the hospital had a lower hazard for the composite outcome compared with patients that initiated enalapril in the hospital and then had a delayed initiation of sacubitril/valsartan 8 weeks later (hazard ratio, 0.69; 95% CI 0.49-0.97).<br />Conclusions and Relevance: Switching patients' treatment from enalapril to sacubitril/valsartan at 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with heart failure with reduced ejection fraction and a recent hospitalization for ADHF.<br />Trial Registration: ClinicalTrials.gov identifier: NCT02554890.

Details

Language :
English
ISSN :
2380-6591
Volume :
5
Issue :
2
Database :
MEDLINE
Journal :
JAMA cardiology
Publication Type :
Academic Journal
Accession number :
31825471
Full Text :
https://doi.org/10.1001/jamacardio.2019.4665