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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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Cost‐related medication nonadherence among adolescent and young adult cancer survivors
Kaul, S., Avila, J. C., Mehta, H. B., Rodriguez, A. M., Kuo, Y., & Kirchhoff, A. C. (2017) · Cancer · doi:10.1002/cncr.30648 · Cited by 83
“higher mortality.(6,34) Our results demonstrate the need to investigate nonadherence among AYA cancer survivors in greater detail (ie, for specific drugs/therapy) and to identify targeted strategies to improve adherence.”
BackgroundResultAssociation Between Nocturnal Hypoxemia and Cancer Incidence in Patients Investigated for OSA
Justeau, G., Gervès‐Pinquié, C., Vaillant, M. L., Trzépizur, W., Meslier, N., Goupil, F., Pigeanne, T., Launois, S. H., Leclair‐Visonneau, L., Masson, P., et al. (2020) · CHEST Journal · doi:10.1016/j.chest.2020.06.055 · Cited by 89
de Thurah, A. L., Nørgaard, M., Harder, I., & Stengaard‐Pedersen, K. (2009) · Rheumatology International · doi:10.1007/s00296-009-1160-8 · Cited by 83
“Compliance to drug therapy may be associated with an overall healthier behaviour [ 33 ], i.e.”
BackgroundBurnier, M. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01540 · Cited by 78
“In the field of cardiovascular medicine, several analyses have demonstrated that higher MPR or PDC are associated with a lower mortality (Simpson et al., 2006) and a reduced risk of cardiovascular complications such as stroke, congestive heart failure, or coronary events (Perreault et al.”
BackgroundFactors involved in the discontinuation of antihypertensive drug therapy
Mancia, G., Zambon, A., Soranna, D., Merlino, L. G., & Corrao, G. (2014) · Journal of Hypertension · doi:10.1097/hjh.0000000000000222 · Cited by 81
Adherence and patients’ experiences with the use of oral anticancer agents
Timmers, L., Boons, C. C. L. M., Kropff, F., van de Ven, P. M., Swart, E. L., Smit, E. F., Zweegman, S., Kroep, J. R., Timmer-Bonte, J. N. H., Boven, E., et al. (2013) · Acta Oncologica · doi:10.3109/0284186x.2013.844353 · Cited by 79
Edgcomb, J. B., & Zima, B. T. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2018.0040 · Cited by 78
“The definition of adherence varied across studies, a limitation raised by other meta-analyses and systematic reviews of patient adherence (DiMatteo et al. 2000; Simpson et al. 2006).”
Shang, P., Liu, G. G., Zheng, X., Ho, P. M., Hu, S., Li, J., Jiang, Z., Li, X., Bai, X., Gao, Y., et al. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.011793 · Cited by 81
Drotar, D. (2009) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e3181a7ed42 · Cited by 78
“Two clinically relevant questions were the focus of this review: (1) how do children with chronic illness and parents perceive their pediatric providers’ behaviors? (2) how do pediatricians’ behaviors in chronic illness management relate to treatment adherence? The results of this review are organized in the following…”
BackgroundPoor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence
Rabenda, V., Hiligsmann, M., & Reginster, J. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560903140533 · Cited by 78
“Moreover, analysis of the relationship between mortality in clinical studies and adherence to treatment regardless of indication and diagnosis has proved that good adherence is associated with lower mortality [72].”
BackgroundTremlett, H. L., van der Mei, I. A. F., Pittas, F., Blizzard, L., Paley, G., Dwyer, T., Taylor, B. V., & Ponsonby, A. (2008) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1593 · Cited by 78
Kelly, M., McCarthy, S., & Sahm, L. J. (2014) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-014-1761-3 · Cited by 82
“Good medication adherence is linked to positive health outcomes [4, 5].”
Kripalani, S. B., Schmotzer, B. J., & Jacobson, T. A. (2012) · Journal of General Internal Medicine · doi:10.1007/s11606-012-2136-z · Cited by 80
Bramlage, P., & Hasford, J. (2009) · Cardiovascular Diabetology · doi:10.1186/1475-2840-8-18 · Cited by 77
“The absolute amount of blood pressure reduction in mmHg over the short term can however not be extrapolated to the degree of protection against hypertensive end organ damage because low patient's compliance and poor persistence with treatment may lead to early discontinuation of treatment in clinical practice [1-3].”
BackgroundAbell, B., Glasziou, P., & Hoffmann, T. (2017) · Sports Medicine - Open · doi:10.1186/s40798-017-0086-z · Cited by 86
“While exercise adherence in itself may be an important driver behind reduced mortality, our findings could also be attributed to a phenomenon known as the ‘healthy adherer effect’ [127].”
BackgroundLong-term persistence with statin therapy: A nationwide register study in Finland
Helin-Salmivaara, A., Lavikainen, P., Korhonen, M. J., Halava, H., Junnila, S. Y. T., Kettunen, R., Neuvonen, P. J., Martikainen, J. E., Ruokoniemi, P., & Saastamoinen, L. K. (2008) · Clinical Therapeutics · doi:10.1016/j.clinthera.2008.12.003 · Cited by 76
Hannan, E., Samadashvili, Z., Cozzens, K., Walford, G., Jacobs, A., Holmes, D., Stamato, N., Gold, J., Sharma, S. K., Venditti, F. J., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.071811 · Cited by 87
The association between coeliac disease and cardiovascular disease
Li, W., Spiers, E. M., REYNOLDS, N., WALSH, S., Fahey, T. P., & MacDonald, T. M. (2007) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03594.x · Cited by 75
Doumouras, A. G., Hong, D., Lee, Y., Tarride, J., Paterson, J. M., & Anvari, M. (2020) · Annals of Internal Medicine · doi:10.7326/m19-3925 · Cited by 75
“High-quality studies have demonstrated that adherence to placebo therapy is associated with lower mortality rate, but it would be difficult to extrapolate such data to bariatric surgery (31).”
BackgroundAtlantis, E. E., Browning, C. J., Sims, J., & Kendig, H. L. (2009) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2409 · Cited by 81
“This is particularly important knowledge for clinical care of older people, given that they experience the highest burden of chronic disease and prescription medications (Dunstan et al., 2001; Chapman et al., 2005; Simpson et al., 2006).”
BackgroundBouwman, L., Eeltink, C., Visser, O. J., Janssen, J. J. W. M., & Maaskant, J. M. (2017) · BMC Cancer · doi:10.1186/s12885-017-3735-1 · Cited by 75
“Ultimately, depending on the nature of the medication, this may lead to serious complications like infections, graftversus-host-disease and progression or relapse of the underlying malignancy [11, 12].”
BackgroundPasma, A., Schenk, C. V., Timman, R., Busschbach, J. J. V., van den Bemt, B. J. F., Molenaar, E. T. H., van der Laan, W. H., Schrauwen, S. L., Spijker, A. V., & Hazes, J. M. W. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0801-4 · Cited by 74
“The outcomes of this study might have been subjected to the ‘adherer effect’ [19].”
BackgroundAdherence to Quality Indicators and Survival in Patients With Breast Cancer
Cheng, S. H., Wang, C.-H. J., Lin, J.-L., Horng, C., Lu, M., Asch, S. M., Hilborne, L. H., Liu, M.-C., Chen, C., & Huang, A. T. (2009) · Medical Care · doi:10.1097/mlr.0b013e3181893c4a · Cited by 74
Camp, Y. P. M. V., Rompaey, B. V., & Elseviers, M. M. (2012) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-012-1419-y · Cited by 83
“Poor medication adherence severely attenuates optimum clinical benefit, and is hence associated with poorer outcomes [14].”
BackgroundKrummenacher, I., Cavassini, M. L., Bugnon, O., & Schneider, M. P. (2011) · AIDS Care · doi:10.1080/09540121.2010.525613 · Cited by 74
“Long-term optimal medication adherence to antiretroviral therapy (ART) is essential to reduce the morbidity and mortality of HIV infection (Paterson et al., 2000; Simpson et al., 2006; Wood et al., 2004).”
BackgroundThe relativity of ‘placebos’: defending a modified version of Grünbaum’s definition
Howick, J. (2016) · Synthese · doi:10.1007/s11229-015-1001-0 · Cited by 74
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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