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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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“Better adherence to cardioprotective treatments, in turn, has been shown to translate into reduced morbidity and mortality [7, 8].”
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“Subsequent randomized clinical trials of cardiovascular agents supported this finding,((11,12)) and it was confirmed again in a meta-analysis of the placebo arms from eight studies containing 19,633 participants.((13)) These findings of decreased mortality in good adherers of placebo may be explained by the so-called…”
ResultMedication Adherence and its Predictors in Community Elderly Patients with Hypertension
Bae, S.-G., Jeon, H. J., Yang, H. S., Kim, B. K., & Park, K. (2015) · Daehan imsang geon-gang jeungjin hakoeji/Daehan imsang geon'gang jeungjin haghoeji · doi:10.15384/kjhp.2015.15.3.121 · Cited by 19
Impact of workplace health services on adherence to chronic medications.
Sherman, B. W., Frazee, S. G., Fabius, R. J., Broome, R. A., Manfred, J., & Davis, J. (2009) · PubMed · Cited by 18
Roughead, E. E., Ramsay, E. N., Priess, K., Barratt, J. D., Ryan, P., & Gilbert, A. L. (2008) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1687 · Cited by 19
Kamau, A., Musau, M. M., Mwakio, S., Amadi, D., Nyaguara, A., Bejon, P., Seale, A. C., Berkley, J. A., & Snow, R. W. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciac509 · Cited by 19
“Observational studies are always subject to “adherer effects” [47].”
Workplace Social Capital and Adherence to Antihypertensive Medication: A Cohort Study
Oksanen, T., Kawachi, I. I., Kouvonen, A. M., Suzuki, E., Takao, S., Sjösten, N., Virtanen, M., Pentti, J., Vahtera, J., & Mika Kivimaki, B. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024732 · Cited by 18
“Finally, there may be a tendency of those employees whose adherence is poor to develop complications of high blood pressure and to leave employment [10,50].”
BackgroundIihara, N., Nishio, T., Okura, M., Anzai, H., Kagawa, M., Houchi, H., & Kirino, Y. (2013) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12100 · Cited by 18
Effects of a three party healthcare network on the incidence levels of drug related problems
Fiß, T., Meinke‐Franze, C., van den Berg, N., & Hoffmann, W. U. (2013) · International Journal of Clinical Pharmacy · doi:10.1007/s11096-013-9804-x · Cited by 18
“[31] with 46,847 patients revealed that better adherence is associated with lower overall mortality (OR = 0.”
BackgroundFamily history of cardiovascular disease and influence on statin therapy persistence
Citarella, A., Kieler, H., Sundström, A., Linder, M., Wettermark, B., Berglind, I. A., & Andersen, M. T. (2014) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-014-1659-0 · Cited by 19
“that poor adherence and persistence to the medication regimen is a major factor behind the lack of effect [2–7].”
BackgroundA pilot study on cost-related medication nonadherence in Ontario.
Zheng, B., Poulose, A., Fulford, M. B., & Holbrook, A. M. (2012) · PubMed · Cited by 18
Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort
Melesse, D. Y., Marrie, R. A., Blanchard, J., Yu, B. N., & Evans, C. D. (2017) · Patient Preference and Adherence · doi:10.2147/ppa.s138263 · Cited by 17
López-Jaramillo, P. A., González‐Gómez, S., Zarate-Bernal, D., Serrano, A., Atuesta, L., Clausen, C., Castro-Valencia, C., Camacho, P. A., & Otero, J. A. (2018) · Therapeutic Advances in Cardiovascular Disease · doi:10.1177/1753944718764588 · Cited by 18
The placebo and its effects: A psychoneuroendocrinological perspective
Gaab, J. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.08.008 · Cited by 18
O'Brien, E. C., McCoy, L. A., Thomas, L. E., Peterson, E. D., & Wang, T. Y. (2015) · American Heart Journal · doi:10.1016/j.ahj.2015.04.011 · Cited by 18
Measures of Adherence to Oral Hypoglycemic Agents at the Primary Care Clinic Level
Wong, E. S., Piette, J. D., Liu, C., Perkins, M. W., Maciejewski, M. L., Jackson, G. L., Blough, D. K., Fihn, S. D., Au, D. H., & Bryson, C. L. (2012) · Medical Care · doi:10.1097/mlr.0b013e318249cb74 · Cited by 18
“There is also evidence suggesting those who exhibit better adherence are inherently healthier.(42) Because absolute differences in the proportion of adherent patients across clinics are large, the role of the facility may still be important even when the proportion of variance explained by facility effects is low, as…”
BackgroundPatients’ understanding of prescription instructions in a semi-urban setting in Cameroon
Mbuagbaw, L. C. E., & Ndongmanji, E. (2012) · Patient Education and Counseling · doi:10.1016/j.pec.2012.01.006 · Cited by 18
Influenza Vaccinations for All Pregnant Women? Better Evidence Is Needed
Donzelli, A. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15092034 · Cited by 17
“Subjects who adhere to preventive therapies are at the same time more likely to engage in behaviors consistent with a healthy lifestyle than are patients who do not adhere to such treatments [7,8].”
BackgroundDoctors’ views and strategies to improve patients’ adherence to medication
Yfantopoulos, J., Protopapa, M., Chantzaras, A. E., & Yfantopoulos, P. (2021) · HORMONES · doi:10.1007/s42000-021-00294-2 · Cited by 17
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Tolley, A., Grewal, K., Weiler, A., Papameletiou, A. M., Hassan, R., & Basu, S. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1183818 · Cited by 19
The Cost-Effectiveness of Sleep Apnea Management
Pendharkar, S. R., Kaambwa, B., & Kapur, V. K. (2024) · CHEST Journal · doi:10.1016/j.chest.2024.04.024 · Cited by 17
Adisa, R., Ufuah, U. F., & Ige, O. M. (2024) · BMC Health Services Research · doi:10.1186/s12913-024-11683-9 · Cited by 18
“Studies have shown that optimal adherence to prescribed therapies and appropriate use of inhaler are important determinants for asthma and COPD control, as well as achievement of positive health outcomes [18, 25, 56, 57].”
BackgroundChatterjee, S., Udell, J. A., Sardar, P., Lichstein, E., & Ryan, J. J. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.03.012 · Cited by 17
Estimating the Impact of Oral Diabetes Medication Adherence on Medical Costs in VA
Wong, E. S., Bryson, C. L., Hebert, P. L., & Liu, C. (2014) · Annals of Pharmacotherapy · doi:10.1177/1060028014536981 · Cited by 17
“For example, adherence may be correlated with other healthy behaviors that result in lower medical costs.(11) Analyses may overstate the economic benefits of adherence on medical costs if these confounders are not accounted for.”
BackgroundTriple Combination Therapy for Global Cardiovascular Risk: Atorvastatin, Perindopril, and Amlodipine
Bertrand, M. E., Vlachopoulos, C. V., & Mourad, J. (2016) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-016-0175-2 · Cited by 18
Counter, D., Stewart, D. C., MacLeod, J., & McLay, J. S. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13220 · Cited by 17
Ferrières, J., Lautsch, D., Ambegaonkar, B. M., Ferrari, G. M. D., Vyas, A., Baxter, C. A., Bash, L. D., Velkovski-Rouyer, M., Horack, M., Almahmeed, W. A., et al. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.06.008 · Cited by 18
“The situation is further complicated by decreasing adherence to secondary prevention treatments after discharge from hospital [8-14].”
BackgroundNguyen, T. N., Cao, H. T. K., Quach, D. N., Le, K., Sam, A. X., Pham, S. T., Nguyen, T. H., Pham, T. T., & Taxis, K. (2019) · Tropical Medicine & International Health · doi:10.1111/tmi.13312 · Cited by 17
“Nonadherence to medicines has a considerable impact on patients’ health outcomes (increasing morbidity and mortality) and the healthcare system (increasing use of services and hospital readmissions) [3,4].”
BackgroundEvans, C. D., Marrie, R. A., Yao, S., Zhu, F., Walld, R., Tremlett, H. L., Blackburn, D. F., & Kingwell, E. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-043930 · Cited by 17
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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