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A meta-analysis of the association between adherence to drug therapy and mortality
Open accessAbstract
OBJECTIVE: To evaluate the relation between adherence to drug therapy, including placebo, and mortality. DESIGN: Meta-analysis of observational studies. DATA SOURCES: Electronic databases, contact with investigators, and textbooks and reviews on adherence. Review methods Predefined criteria were used to select studies reporting mortality among participants with good and poor adherence to drug therapy. Data were extracted for disease, drug therapy groups, methods for measurement of adherence rate, definition for good adherence, and mortality. RESULTS: Data were available from 21 studies (46,847 participants), including eight studies with placebo arms (19,633 participants). Compared with poor adherence, good adherence was associated with lower mortality (odds ratio 0.56, 95% confidence interval 0.50 to 0.63). Good adherence to placebo was associated with lower mortality (0.56, 0.43 to 0.74), as was good adherence to beneficial drug therapy (0.55, 0.49 to 0.62). Good adherence to harmful drug therapy was associated with increased mortality (2.90, 1.04 to 8.11). CONCLUSION: Good adherence to drug therapy is associated with positive health outcomes. Moreover, the observed association between good adherence to placebo and mortality supports the existence of the "healthy adherer" effect, whereby adherence to drug therapy may be a surrogate marker for overall healthy behaviour.
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“In addition, as adherence with placebo also improves survival, 524 physicians should be aware that adherence to medication may reflect generally better health behaviour.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [524]
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Chapman, S., & Chan, A. H. Y. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1465059 · Cited by 37
Hendrychova, T., Vytrisalova, M., Smahelova, Vlček, J., & Kubena (2013) · Patient Preference and Adherence · doi:10.2147/ppa.s47750 · Cited by 25
MacKenzie-Smith, L., Marchi, P., Thorne, H. C., Timeus, S., Young, R., & Calvé, P. L. (2018) · Inflammatory Intestinal Diseases · doi:10.1159/000493346 · Cited by 25
Coca, A., Kreutz, R. H., Manolis, A. J., & Mancia, G. (2020) · Journal of Hypertension · doi:10.1097/hjh.0000000000002464 · Cited by 25
Desta, L., Khedri, M., Jernberg, T., Andell, P., Mohammad, M. A., Hofman‐Bang, C., Erlinge, D., Spaak, J., & Persson, H. (2020) · ESC Heart Failure · doi:10.1002/ehf2.13079 · Cited by 26
“This is consistent with the finding of previous studies.(34) Contrary to the findings of other studies(37) and the questioned place of beta‐blocker treatment long after AMI in the modern reperfusion era,(16,40) we observed a favourable association with outcome even in patients with NEF without HF as shown by survival…”
ResultImproving Medication Management Among At-Risk Older Adults
Martin, D., Kripalani, S. B., & DuRapau, V. J. (2012) · Journal of Gerontological Nursing · doi:10.3928/00989134-20120507-50 · Cited by 26
Stetler, C. (2013) · Psychology and Health · doi:10.1080/08870446.2013.830721 · Cited by 27
“A meta-analysis of randomised controlled trials (RCTs) involving a variety of medications found that good adherence to a placebo was associated with a roughly 50% reduction in mortality risk, equal to that associated with good adherence to an effective active drug (Simpson et al., 2006).”
BackgroundStröm, O., Landfeldt, E., & Garellick, G. (2014) · Osteoporosis International · doi:10.1007/s00198-014-2900-5 · Cited by 25
“Further, it has been argued that a lower fracture risk in patients remaining longer on treatment could arise from a “healthy adherer effect” [15] where patients who persist with therapy are generally of better health compared with patients who discontinue therapy early.”
BackgroundChamorro, M. Á. R., García‐Jiménez, E., Amariles, P., Chamorro, A. R., Merino, E. M. P., Martínez, F. M., & Dáder, M. J. F. (2011) · Atención Primaria · doi:10.1016/j.aprim.2010.05.006 · Cited by 25
Blinding in trials of interventional procedures is possible and worthwhile
Wartolowska, K. A., Beard, D. J., & Carr, A. J. (2017) · F1000Research · doi:10.12688/f1000research.12528.2 · Cited by 45
Mancia, G., Coca, A., Chazova, I. E., Girerd, X. J., Haller, H. G., Pauletto, P., Pupek‐Musialik, D., & Svyshchenko, Y. (2014) · Journal of Hypertension · doi:10.1097/hjh.0000000000000239 · Cited by 24
“However, as known from previous studies [23,26,29,33], the placebo effect was much less pronounced with home BP measurements, which made the difference of home BP effects by active treatments and placebo more consistent.”
ResultHerrera, J. C. M., Morales‐Asencio, J. M., Fernández‐Gallego, M. C., Cobos, E. B., & Romero, A. (2011) · Anales del Sistema Sanitario de Navarra · doi:10.4321/s1137-66272011000100006 · Cited by 23
Lousdal, M. L., Lash, T. L., Flanders, W. D., Brookhart, M. A., Kristiansen, I. S., Kalager, M., & Støvring, H. (2020) · International Journal of Epidemiology · doi:10.1093/ije/dyaa029 · Cited by 24
Michalski, P., Kasprzak, M., Siedlaczek, M., & Kubica, A. (2020) · Medical Research Journal · doi:10.5603/mrj.a2020.0023 · Cited by 24
The Impact of Non-Adherence to Antihypertensive Drug Therapy
Gardezi, S. K., Aitken, W. W., & Jilani, M. H. (2023) · Healthcare · doi:10.3390/healthcare11222979 · Cited by 24
“This relationship between poor adherence to medications and therapeutic lifestyle changes has been termed the “healthy adherer effect”, wherein patients who are more apt to take prescribed medications have better health outcomes above and beyond those attributable to their medications [2].”
BackgroundKripalani, S. B., Osborn, C. Y., Vaccarino, V., & Jacobson, T. A. (2011) · Medical Education Online · doi:10.3402/meo.v16i0.7133 · Cited by 25
“This can lead to poor control of chronic diseases and worse health outcomes, including higher mortality (3, 4).”
BackgroundPhysician ownership of complementary medical services
Chen, B., Gertler, P., & Yang, C. (2016) · Journal of Public Economics · doi:10.1016/j.jpubeco.2016.09.005 · Cited by 23
Gackowski, M., Jasińska-Stroschein, M., Osmałek, T. Z., & Waszyk-Nowaczyk, M. (2024) · Medical Science Monitor · doi:10.12659/msm.944605 · Cited by 32
“However, this problem is not limited to cardiac disease and generally affects patients [15-17].”
BackgroundBöhm, M., Lloyd, S. M., Ford, I., BORER, J. S., Ewen, S., Laufs, U., Mahfoud, F., Lopez-Sendon, J. L., Ponikowski, P. P., Tavazzi, L., et al. (2016) · European Journal of Heart Failure · doi:10.1002/ejhf.493 · Cited by 23
Development and validation of the WebAd-Q Questionnaire to monitor adherence to HIV therapy
Vale, F. C., Helena, E. T. D. S., Santos, M. A., Carvalho, W. M. D. E. S., Menezes, P. R., Basso, C. R., da Silva, M. H., Alves, A. M., & Nemes, M. I. B. (2018) · Revista de Saúde Pública · doi:10.11606/s1518-8787.2018052000337 · Cited by 23
Carratalá-Munuera, C., Cortés-Castell, E., Márquez-Contreras, E., Castellano, J. M., Perez-Paramo, M., López‐Pineda, A., & Gil-Guillen, V. F. (2022) · Patient Preference and Adherence · doi:10.2147/ppa.s319084 · Cited by 23
“Poor therapeutic adherence is a serious problem for properly approaching chronic patients in our healthcare system.(15) This is due to the existence of a series of barriers that healthcare professionals encounter in their daily clinical practice that make it difficult to integrate protocols for therapeutic adherence f…”
BackgroundMafruhah, O. R., Huang, Y., & Lin, H. (2023) · Journal of Neurology · doi:10.1007/s00415-023-11601-9 · Cited by 26
Basso, C. R., Helena, E. T. D. S., Caraciolo, J. M. D. M., Paiva, V. S. F., & Nemes, M. I. B. (2012) · AIDS and Behavior · doi:10.1007/s10461-012-0175-4 · Cited by 23
Yusuf, A., Weinhandl, E. D., & Peter, W. L. S. (2014) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2013.11.015 · Cited by 23
Metadata
- Authors
- Simpson, S. H., Eurich, D. T., Majumdar, S. R., Padwal, R. S., Tsuyuki, R. T., Varney, J., & Johnson, J. A.
- Affiliations
- University of Alberta (CA)
- Institute of Health Economics (CA)
- Corresponding author
- Simpson, Scot H
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2006-06-21
- Volume
- 333
- Issue
- 7557
- Pages
- 15
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC1488752
- OpenAlex
- W2147982456
- Cited by
- 1,353
- References
- 39
- Citations by year
- 2026: 37 · 2025: 40 · 2024: 57 · 2023: 56 · 2022: 55 · 2021: 83 · 2020: 55 · 2019: 74 · 2018: 90 · 2017: 91 · 2016: 69 · 2015: 71 · 2014: 83 · 2013: 77 · 2012: 86
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BMJ (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Health Sciences › Health Professions › Pharmacy › Pharmacy and Medical Practices
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- medication adherence, pharmacotherapy, mortality, adherence measurement methods
- MeSH terms
- Drug Therapy, Epidemiologic Methods, Humans, Patient Compliance, Prognosis, Randomized Controlled Trials as Topic
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