Sacubitril/valsartan initiation among veterans who are renin-angiotensin-aldosterone system inhibitor naïve with heart failure and reduced ejection fraction

April F. Mohanty, Emily B. Levitan, Jordan B. King, John A. Dodson, Orly Vardeny, James Cook, Jennifer S. Herrick, Tao He, Olga V. Patterson, Patrick R. Alba, Patricia A. Russo, Engels N. Obi, Michelle E. Choi, James C. Fang, Adam P. Bress

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2 Scopus citations


BACKGROUND: Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, received US Food and Drug Administration approval in 2015 for heart failure with reduced ejection fraction (HFrEF). Our objective was to describe the sacubitril/valsartan initiation rate, associated characteristics, and 6-month follow-up dosing among veterans with HFrEF who are renin-angiotensin-aldosterone system inhibitor (RAASi) naïve. METHODS AND RESULTS: Retrospective cohort study of veterans with HFrEF who are RAASi naïve defined as left ventricular ejection fraction (LVEF) ≤40%; ≥1 in/outpatient heart failure visit, first RAASi (sacubitril/valsartan, angiotensin-converting en-zyme inhibitor [ACEI]), or angiotensin-II receptor blocker [ARB]) fill from July 2015 to June 2019. Characteristics associated with sacubitril/valsartan initiation were identified using Poisson regression models. From July 2015 to June 2019, we identified 3458 sacubitril/valsartan and 29 367 ACEI or ARB initiators among veterans with HFrEF who are RAASi naïve. Sacubitril/ valsartan initiation increased from 0% to 26.5%. Sacubitril/valsartan (versus ACEI or ARB) initiators were less likely to have histories of stroke, myocardial infarction, or hypertension and more likely to be older and have diabetes mellitus and lower LVEF. At 6-month follow-up, the prevalence of ≥50% target daily dose for sacubitril/valsartan, ACEI, and ARB initiators was 23.5%, 43.2%, and 47.1%, respectively. CONCLUSIONS: Sacubitril/valsartan initiation for HFrEF in the Veterans Administration increased in the 4 years immediately following Food and Drug Administration approval. Sacubitril/valsartan (versus ACEI or ARB) initiators had fewer baseline cardiovascular comorbidities and the lowest proportion on ≥50% target daily dose at 6-month follow-up. Identifying the reasons for lower follow-up dosing of sacubitril/valsartan could support guideline recommendations and quality improvement strategies for patients with HFrEF.

Original languageEnglish (US)
Article numbere020474
JournalJournal of the American Heart Association
Issue number20
StatePublished - Oct 19 2021

Bibliographical note

Funding Information:
This work was supported by an academic–industry collaboration between the University of Utah, Salt Lake City, UT, and Novartis Pharmaceuticals Corporation, East Hanover, NJ. This work was also supported using resources and facilities at the Veterans Affairs Salt Lake City Health Care System with funding from the VA Informatics and Computing Infrastructure, VA HSR RES 13-457, US Department fo Veterans Affairs.

Funding Information:
Dr Mohanty is supported by the Veterans Health Administration Office of Health Services Research and Development, Career Development Award (IK2HX002609) and received research support from Novartis. Dr Vardeny has consulted for Novartis. Drs. Vardeny and Bress received research support from Novartis. Dr Bress also reported receiving grants from Amarin outside the submitted work. Drs. Russo and Obi were employees of Novartis during the conduct of this study. Dr Choi was an employee of the University of Maryland Baltimore, and provided services to Novartis. Dr Levitan received consulting fees for this work, receives research funding from Amgen, and has served on Amgen advisory boards. Dr King and Mr. He received research support to his institution from Novartis. Dr Patterson and Mr. Alba have received research grants from the following for-profit organizations through the University of Utah or Western Institute for Biomedical Research: Anolinx LLC, AstraZeneca Pharmaceuticals LP, Genentech Inc., Genomic Health, Inc., Gilead Sciences Inc., Janssen Pharmaceuticals, Inc., Novartis International AG, and PAREXEL International Corporation. Dr Feng has received consulting fees from Novartis and Amgen outside the submitted work. Dr Dodson has no disclosures to report.

Funding Information:
We accessed demographic, pharmacy, clinical, and medical history data from the national VHA Corporate Data Warehouse. Data were accessed using the VA Informatics and Computing Infrastructure workspace. This study was sponsored by Novartis Pharmaceuticals Corporation. The University of Utah Institutional Review Board and the Salt Lake City Veterans Affairs Health Care System Research and Development Office approved this study. Informed consent was not required for this study.

Publisher Copyright:
© 2021 The Authors and Novartis Pharmaceuticals. Published on behalf of the American Heart Association, Inc., by Wiley.


  • Angiotensin receptor neprilysin inhibitor
  • Heart failure
  • Medication
  • Reduced ejection fraction
  • Titration


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