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The AWAKE-HF Study: Sacubitril/Valsartan Impact on Daily Physical Activity and Sleep in Heart Failure

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Abstract

Background

AWAKE-HF evaluated the effect of the initiation of sacubitril/valsartan versus enalapril on activity and sleep using actigraphy in patients who have heart failure with reduced ejection fraction (HFrEF).

Methods

In this randomized, double-blind study, patients with HFrEF (n = 140) were randomly assigned to sacubitril/valsartan or enalapril for 8 weeks, followed by an 8-week open-label phase with sacubitril/valsartan. Primary endpoint was change from baseline in mean activity counts during the most active 30 min/day at week 8. The key secondary endpoint was change in mean nightly activity counts/minute from baseline to week 8. Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23) was an exploratory endpoint.

Results

There were no detectable differences between groups in geometric mean ratio of activity counts during the most active 30 min/day at week 8 compared with baseline (0.9456 [sacubitril/valsartan:enalapril]; 95% confidence interval [CI] 0.8863–1.0088; P = 0.0895) or in mean change from baseline in activity during sleep (difference: 2.038 counts/min; 95% CI − 0.062 to 4.138; P = 0.0570). Change from baseline to week 8 in KCCQ-23 was 2.89 for sacubitril/valsartan and 4.19 for enalapril, both nonsignificant.

Conclusions

In AWAKE-HF, no detectable differences in activity and sleep were observed when comparing sacubitril/valsartan with enalapril in patients with HFrEF using a wearable biosensor.

Clinical trial registration

ClinicalTrials.gov, NCT02970669.

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Acknowledgements

Visualization of data was provided by Jonas Dorn of Novartis (Basel, Switzerland) and expertise regarding sleep testing was provided by Michael Coppola, MD, of NovaSom (Glen Burnie, MD, USA). Medical writing and editorial assistance were provided by Janel Torsiello, PharmD, and Traci Stuve, MA, of ApotheCom (Yardley, PA, USA), funded by Novartis Pharmaceuticals Corporation.

Funding

The AWAKE-HF study was sponsored and funded by Novartis Pharmaceuticals Corporation (East Hanover, NJ, USA) and was designed through a collaboration of the sponsor and the study’s steering committee. The sponsor provided consultant compensation to the steering committee member authors for their trial-related activities.

Author information

Author notes

  1. Emmanuel Fombu

    Present address: Locust Walk Partners, 610 W 42nd St., New York, NY, 10036, USA

Authors and Affiliations

  1. Department of Cardiology, Cedars-Sinai Medical Care Foundation, Cedars-Sinai Heart Institute, 8501 Wilshire Ave, Beverly Hills, California, 90211, United States

    Raj M. Khandwalla

  2. Novartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ, 07936, USA

    Daniel Grant

  3. Department of Cardiology, Cedars-Sinai, 127 S San Vicente Blvd a3600, Los Angeles, CA, 90048, USA

    Kade Birkeland

  4. Division of Cardiovascular Medicine, Scripps Clinic, 10666 N Torrey Pines Rd, San Diego, CA, 92037, USA

    J. Thomas Heywood

  5. Previously Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Emmanuel Fombu

  6. Division of Pulmonary, Critical Care, and Sleep Medicine, San Diego School of Medicine, University of California, 4520 Executive Drive, San Diego, CA, 92121, USA

    Robert L. Owens

  7. Digital Medicine, Scripps Research Translational Science Institute, 3344 North Torrey Pines Court, Suite 300, San Diego, CA, 92037, USA

    Steven R. Steinhubl

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Consortia

for the AWAKE-H. F. Study Investigators

Corresponding author

Correspondence to Raj M. Khandwalla.

Ethics declarations

Conflict of interest

Raj M. Khandwalla has served as a consultant for Novartis Pharmaceuticals Corporation and has received a research grant from General Electric. Kade Birkeland has served as a consultant for Novartis Pharmaceuticals Corporation. J. Thomas Heywood has served as a consultant for Actelion Pharmaceuticals, Medtronic, and Abbott; was a speaker for Actelion Pharmaceuticals, Medtronic, Abbott, Otsuka, and Novartis Pharmaceuticals Corporation; has received grant funding from Medtronic, Abbott, and Impedimed; and has received fellowship grant support from Abbott. Robert L. Owens has received honoraria and travel reimbursements from ResMed, LLC, and Itamar Medical and has served as a consultant for Novartis Pharmaceuticals Corporation. Steven Steinhubl has received financial compensation from Novartis Pharmaceuticals Corporation for serving as an adviser. Emmanuel Fombu was an employee of Novartis Pharmaceuticals at the time of this study. Daniel Grant is an employee of Novartis Pharmaceuticals.

Ethics approval

Not applicable

Consent to participate

All participants in the trial signed an informed consent upon enrollment.

Consent for publication

All co-authors have consented for publication.

Availability of data and materials

Data and materials were made available to the co-investigators.

Code availability

Not applicable.

Author Contributions

All authors contributed to the conception and design of the study and/or data analysis/interpretation, drafting, and/or critical review of the manuscript, and all provided final approval to submit the manuscript for publication. RMK wrote the first draft of the manuscript, and the other authors, as part of the steering committee, revised subsequent drafts. Medical writing and editing assistance was provided by ApotheCom (Yardley, PA, USA), funded by Novartis Pharmaceuticals Corporation. All authors agree to be accountable for all aspects of the work and to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. A full list of all investigators and institutions involved in the study is provided in Table S1 in the ESM.

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Khandwalla, R.M., Grant, D., Birkeland, K. et al. The AWAKE-HF Study: Sacubitril/Valsartan Impact on Daily Physical Activity and Sleep in Heart Failure. Am J Cardiovasc Drugs 21, 241–254 (2021). https://doi.org/10.1007/s40256-020-00440-y

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