Declining public health burden of digoxin toxicity from 1991 to 2004
Abstract
We hypothesized that digoxin toxicity has declined in recent years, and that the decline is accompanied by reductions in overall utilization and dose. To analyze trends in digoxin toxicity and utilization from 1991 to 2004, we used surveys from the National Center for Health Statistics and Medicaid data in the United States and The Health Improvement Network (THIN) database in the United Kingdom. There was a significant decline in digoxin toxicity hospitalizations in the United States and a decline in ambulatory digoxin toxicity in the United Kingdom. The study demonstrated a reduction in the use of digoxin in the United States, but found no change in digoxin use in the United Kingdom. Finally, the number of prescriptions written for at least 250 microg decreased in the United States and the United Kingdom. The public health burden of digoxin toxicity declined dramatically from 1991 to 2004 in the United Kingdom and the United States.
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Digoxin use is on the decline amid the emergence of alternative therapies with preferable safety profiles.
“digoxin use is on the decline amid the emergence of alternative therapies with preferable safety profiles (Haynes et al., 2008;Eade et al., 2013).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Haynes et al., 2008
Cites
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
Pitt, B., Zannad, F., Remme, W. J., Cody, R., Castaigne, A., Perez, A., Palensky, J., & Wittes, J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909023411001 · Cited by 9,214 · see citing works
Pitt, B., Remme, W., Zannad, F., Neaton, J., Martinez, F., Roniker, B., Bittman, R., Hurley, S., Kleiman, J., & Gatlin, M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030207 · Cited by 4,941 · see citing works
A comparison of rate control and rhythm control in patients with atrial fibrillation
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa021328 · Cited by 4,405 · see citing works
The effect of digoxin on mortality and morbidity in patients with heart failure
(1997) · New England Journal of Medicine · doi:10.1056/nejm199702203360801 · Cited by 3,016 · see citing works
Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure
Rathore, S. S., Curtis, J. P., Wang, Y., Bristow, M. R., & Krumholz, H. M. (2003) · JAMA · doi:10.1001/jama.289.7.871 · Cited by 772 · see citing works
ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text
Fuster, V., Rydén, L., Cannom, D. S., Crijns, H. J. G. M., Curtis, A. B., Ellenbogen, K. A., Halperin, J. L., Heuzey, J. L., Kay, G. N., Lowe, J. E., et al. (2006) · EP Europace · doi:10.1093/europace/eul097 · Cited by 663 · see citing works
The Polymorphonuclear Leukocyte and the Abdominal Aortic Aneurysm
Tilson, M. D. (2005) · Circulation · doi:10.1161/circulationaha.105.553370 · Cited by 654 · see citing works
Lewis, J. D., Schinnar, R., Bilker, W. B., Wang, X., & Strom, B. L. (2007) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1335 · Cited by 602 · see citing works
Inappropriate Medication Prescribing for Elderly Ambulatory Care Patients
Goulding, M. R. (2004) · Archives of Internal Medicine · doi:10.1001/archinte.164.3.305 · Cited by 291 · see citing works
Feasibility study and methodology to create a quality-evaluated database of primary care data
Bourke, A., Dattani, H., & Robinson, M. (2004) · Journal of Innovation in Health Informatics · doi:10.14236/jhi.v12i3.124 · Cited by 286 · see citing works
Antibiotic Treatment of Children With Sore Throat
Linder, J. A. (2005) · JAMA · doi:10.1001/jama.294.18.2315 · Cited by 198 · see citing works
Clinical benefits of low serum digoxin concentrations in heart failure
Adams, K. F., Gheorghiade, M., Uretsky, B. F., Patterson, J. H., Schwartz, T. A., & Young, J. B. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)01708-4 · Cited by 159 · see citing works
Mahdyoon, H., Battilana, G., Rosman, H., Goldstein, S., & Gheorghiade, M. (1990) · American Heart Journal · doi:10.1016/0002-8703(90)90135-k · Cited by 98 · see citing works
Ma, J., Lee, K., & Stafford, R. S. (2006) · Hypertension · doi:10.1161/01.hyp.0000240931.90917.0c · Cited by 86 · see citing works
Effect of Aging on the Incidence of Digoxin Toxicity
Miura, T., Kojima, R., Sugiura, Y., Mizutani, M., Takatsu, F., & Suzuki, Y. (2000) · Annals of Pharmacotherapy · doi:10.1345/aph.19103 · Cited by 77 · see citing works
WILLIAMSON, K. M., Thrasher, K., Fulton, K. B., LaPointe, N. M. A., Dunham, G. D., Cooper, A. A., Barrett, P. S., & Patterson, J. H. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.22.2444 · Cited by 69 · see citing works
Digoxin Use and Digoxin Toxicity in the Post-DIG Trial Era
Hussain, Z., Swindle, J. P., & Hauptman, P. J. (2006) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2006.02.005 · Cited by 68 · see citing works
Digoxin-Specific Antibody Fragments
Bateman, D. N. (2004) · Toxicological Reviews · doi:10.2165/00139709-200423030-00001 · Cited by 60 · see citing works
The impact of age on risk of adverse drug reactions to digoxin
Pahor, M., Guralnik, J. M., Gambassi, G., Bernabei, R., Carosella, L., & Carbonin, P. (1993) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(93)90099-m · Cited by 39 · see citing works
Quinidine enhances digitalis toxicity at therapeutic serum digoxin levels
Mordel, A., Halkin, H., Zulty, L., Almog, S., & Ezra, . (1993) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1993.51 · Cited by 33 · see citing works
Economic Impact of Digoxin Toxicity
Gandhi, A. J., Vlasses, P. H., Morton, D. J., & Bauman, J. L. (1997) · PharmacoEconomics · doi:10.2165/00019053-199712020-00007 · Cited by 29 · see citing works
Eisenstein, E. L., Yusuf, S., Bindal, V., Bourassa, M. G., Horney, A., Collins, J. F., & Mark, D. B. (2006) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2006.04.002 · Cited by 10 · see citing works
Frequency estimates from prescription drug datasets (revision of #04‐11‐066A)
Lin, S., Lambert, B. L., Tan, H., & Toh, S. (2005) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1149 · Cited by 6 · see citing works
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Angraal, S., Nuti, S. V., Masoudi, F. A., Freeman, J. V., Murugiah, K., Shah, N. D., Desai, N. R., Ranasinghe, I., Wang, Y., & Krumholz, H. M. (2019) · The American Journal of Medicine · doi:10.1016/j.amjmed.2019.04.022 · Cited by 44 · see citing works
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Campia, I., Gazzano, E., Pescarmona, G., Ghigo, D., Bosìa, A., & Riganti, C. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-9018-5 · Cited by 32 · see citing works
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Peters, A. E., Chiswell, K., Hofmann, P., Ambrosy, A. P., & Fudim, M. (2022) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2022.08.004 · Cited by 19 · see citing works
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Dimeski, G., Jones, B. W., Pillans, P. I., Page, C. B., & Brown, N. N. (2014) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2013-1043 · Cited by 7 · see citing works
Du, P., Wang, A., Ma, Y., Jia, A., Li, Y., & Li, X. (2020) · Clinical Therapeutics · doi:10.1016/j.clinthera.2020.07.011 · Cited by 7 · see citing works
Kolev, K. K. (2012) · BMJ Case Reports · doi:10.1136/bcr.01.2012.5582 · Cited by 6 · see citing works
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Du, P., Wang, A., Ma, Y., Jia, A., Li, Y., & Li, X. (2021) · Clinical Therapeutics · doi:10.1016/j.clinthera.2021.02.005 · Cited by 6 · see citing works
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Goh, J. Y., & Siaw, C. (2023) · Malaysian Family Physician · doi:10.51866/tyk.256 · Cited by 1 · see citing works
(2015) · Elsevier eBooks · doi:10.1016/b978-0-444-53717-1.00456-x · Cited by 1 · see citing works
Gebran, N. (2012) · Springer eBooks · doi:10.1007/978-3-642-02202-9_275 · Cited by 1 · see citing works
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LeBlanc, M. R., Pieris, E., & Thompson, M. (2017) · Archives of Medicine · doi:10.21767/1989-5216.1000241
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Bala, P., Reza, A., Ali, M., Khan, M. H., Islam, N., & Reza, S. A. (2021) · Bangladesh Heart Journal · doi:10.3329/bhj.v36i2.56040
Current awareness: Pharmacoepidemiology and drug safety
(2008) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1493
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Aronson, J. K. (2010) · Side effects of drugs annual · doi:10.1016/s0378-6080(10)32017-4
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- Authors
- Haynes, K., Heitjan, D., Kanetsky, P., & Hennessy, S.
- Affiliations
- University of Pennsylvania (US)
- ORCID
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2007-12-19
- Volume
- 84
- Issue
- 1
- Pages
- 90-94
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2165905552
- Cited by
- 49
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 3 · 2017: 6 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 6
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (F32-AG-026180-01, F32AG026180)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- digoxin toxicity, hospitalization, outpatient care, prescribing patterns, public health burden, United States, United Kingdom
- MeSH terms
- Ambulatory Care, Digoxin, United Kingdom, Hospitalization, Humans, Public Health, United States, Databases, Factual, Drug-Related Side Effects and Adverse Reactions
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