Original Research
20 June 2023

Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly: A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial

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Publication: Annals of Internal Medicine
Volume 176, Number 7
Visual Abstract. Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly
In this large primary prevention trial of aspirin in community-dwelling persons aged 70 years or older, daily low-dose aspirin increased the risk of incident anemia by approximately 20%. These findings question preventive use of aspirin in older patients and suggest caution with this practice.

Abstract

Background:

Daily low-dose aspirin increases major bleeding; however, few studies have investigated its effect on iron deficiency and anemia.

Objective:

To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations.

Design:

Post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial. (ClinicalTrials.gov: NCT01038583)

Setting:

Primary/community care in Australia and the United States.

Participants:

Community-dwelling persons aged 70 years or older (≥65 years for Black persons and Hispanic persons).

Intervention:

100 mg of aspirin daily or placebo.

Measurements:

Hemoglobin concentration was measured annually in all participants. Ferritin was measured at baseline and 3 years after random assignment in a large subset.

Results:

19 114 persons were randomly assigned. Anemia incidence in the aspirin and placebo groups was 51.2 events and 42.9 events per 1000 person-years, respectively (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations declined by 3.6 g/L per 5 years in the placebo group and the aspirin group experienced a steeper decline by 0.6 g/L per 5 years (CI, 0.3 to 1.0 g/L). In 7139 participants with ferritin measures at baseline and year 3, the aspirin group had greater prevalence than placebo of ferritin levels less than 45 µg/L at year 3 (465 [13%] vs. 350 [9.8%]) and greater overall decline in ferritin by 11.5% (CI, 9.3% to 13.7%) compared with placebo. A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results.

Limitations:

Hemoglobin was measured annually. No data were available on causes of anemia.

Conclusion:

Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding. Periodic monitoring of hemoglobin should be considered in older persons on aspirin.

Primary Funding Source:

National Institutes of Health and Australian National Health and Medical Research Council.

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Supplemental Material

Supplement.

Study Protocol and Statistical Analysis Plan.

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 176Number 7July 2023
Pages: 913 - 921

History

Published online: 20 June 2023
Published in issue: July 2023

Keywords

Authors

Affiliations

Zoe K. McQuilten, MB, BS, PhD
School of Public Health and Preventive Medicine, Monash University; Department of Haematology, Monash Health; and Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia (Z.K.M.)
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (L.T.P.T., R.W., R.L.W., J.J.M.)
Sant-Rayn Pasricha, MB, BS, PhD https://orcid.org/0000-0002-5502-0434
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria; Diagnostic Haematology, The Royal Melbourne Hospital, Parkville, Victoria; and Clinical Haematology, The Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Parkville, Victoria; and Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia (S.-R.P.)
City of Hope National Medical Center, Duarte, California (A.S.A.)
Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia (M.B.)
Andrew T. Chan, MD, MPH
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts (A.T.C.)
Harvey Jay Cohen, MD
Center for the Study of Aging and Human Development, Duke University, Durham, North Carolina (H.J.C.)
Jessica E. Lockery, MB, BS, PhD https://orcid.org/0000-0001-6664-1239
Cancer, Ageing and Vaccines Research Group, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia (J.E.L.)
Anne M. Murray, MD, MSc
Berman Center for Outcomes and Clinical Research and Department of Medicine, Geriatrics Division, Hennepin Healthcare Research Institute, Minneapolis, Minnesota (A.M.M.)
Mark R. Nelson, MB, BS, PhD https://orcid.org/0000-0001-9941-7161
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia (M.R.N.)
School of Public Health and Preventive Medicine, Monash University; and Clinical Biochemistry Unit, Alfred Pathology Service, Alfred Health, Melbourne, Victoria, Australia (H.G.S.)
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (L.T.P.T., R.W., R.L.W., J.J.M.)
Robyn L. Woods, PhD
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (L.T.P.T., R.W., R.L.W., J.J.M.)
School of Public Health and Preventive Medicine, Monash University; and Clinical Biochemistry Unit, Alfred Pathology Service, Alfred Health, Melbourne, Victoria, Australia (H.G.S.)
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria; and Department of Haematology, Monash Health, Melbourne, Victoria, Australia (E.M.W.).
John J. McNeil, MB, BS, PhD* https://orcid.org/0000-0002-1049-5129
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (L.T.P.T., R.W., R.L.W., J.J.M.)
Acknowledgment: Dr. McQuilten is supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leader Investigator grant (GNT1194811). Drs. Wood and McNeil are supported by NHMRC Leadership Fellow Investigator grants (GNT1177784 and GNT1173690). Dr. Pasricha is supported by an NHMRC Career Development Fellowship (GNT2009047). Dr. Chan is an American Cancer Society Clinical Research Professor. Serum samples were retrieved and prepared for analysis by the ASPREE Biobank staff at Monash University.
Grant Support: ASPREE was funded by grants (U01AG029824 and U19AG062682) from the National Institute on Aging and the National Cancer Institute at the National Institutes of Health, by grants (334047 and 1127060) from the National Health and Medical Research Council of Australia, and by Monash University and the Victorian Cancer Agency. The ASPREE-Anemia analysis was supported by a grant from the Alfred Health Trust. Ferritin measurements were supported by reagent contributions from Abbott Diagnostics and research funds of the Alfred Pathology Service. Drs. Artz and Cohen were supported by a grant from the National Institutes of Health (U01AG034661).
Data Sharing Statement: The following data will be made available with publication: Deidentified participant data. Requests for data access will be via the ASPREE Principal Investigators with details for applications provided through the web site, www.ASPREE.org, and in accord with the NIH policy on data sharing, details available at https://grants.nih.gov/grants/policy/data_sharing. These data will be made available to: Investigators whose proposed use of the data has been approved by a review committee identified for this purpose. Types of Analysis: Analyses required to achieve aims in the approved proposal. Mechanisms: Through the web-based data portal Safe Haven, based at Monash University, Australia.
Corresponding Author: Zoe K. McQuilten, MB, BS, PhD, School of Public Health and Preventive Medicine, Monash University, 553 St. Kilda Road, Melbourne, VIC 3004, Australia; e-mail, [email protected].
Correction: This article was amended on 25 July 2023 to add information to the grant support section. A correction has been published (doi:10.7326/L23-0274).
Author Contributions: Conception and design: H.J. Cohen, J.E. Lockery, J.J. McNeil, Z.K. McQuilten, M.R. Nelson, S.-R. Pasricha, E.M. Wood, R.L. Woods.
Analysis and interpretation of the data: A.S. Artz, M. Bailey, A.T. Chan, H.J. Cohen, J.J. McNeil, Z.K. McQuilten, M.R. Nelson, S.-R. Pasricha, H.G. Schneider, L.T.P. Thao, R. Wolfe, E.M. Wood, R.L. Woods.
Drafting of the article: J.J. McNeil, Z.K. McQuilten, M.R. Nelson, H.G. Schneider, L.T.P. Thao, E.M. Wood.
Critical revision of the article for important intellectual content: A.S. Artz, M. Bailey, A.T. Chan, H.J. Cohen, J.J. McNeil, Z.K. McQuilten, A.M. Murray, M.R. Nelson, S.-R. Pasricha, H.G. Schneider, L.T.P. Thao, R. Wolfe, E.M. Wood, R.L. Woods.
Final approval of the article: A.S. Artz, M. Bailey, A.T. Chan, H.J. Cohen, J.E. Lockery, J.J. McNeil, Z.K. McQuilten, A.M. Murray, M.R. Nelson, S.-R. Pasricha, H.G. Schneider, L.T.P. Thao, R. Wolfe, E.M. Wood, R.L. Woods.
Provision of study materials or patients: M.R. Nelson, H.G. Schneider.
Statistical expertise: M. Bailey, L.T.P. Thao, R. Wolfe.
Obtaining of funding: A.T. Chan, J.J. McNeil, Z.K. McQuilten, M.R. Nelson, H.G. Schneider, R. Wolfe, E.M. Wood, R.L. Woods.
Administrative, technical, or logistic support: A.T. Chan, J.E. Lockery, Z.K. McQuilten, H.G. Schneider.
Collection and assembly of data: J.E. Lockery, M.R. Nelson, H.G. Schneider, R. Wolfe, R.L. Woods.
This article was published at Annals.org on 20 June 2023.
*
Drs. Wood and McNeil are co–senior authors.

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Zoe K. McQuilten, Le Thi Phuong Thao, Sant-Rayn Pasricha, et al. Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly: A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial. Ann Intern Med.2023;176:913-921. [Epub 20 June 2023]. doi:10.7326/M23-0675

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