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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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“A recent systematic review of randomized controlled trials reported that good placebo adherers had about 40% lower cardiovascular [23] and all-cause mortality [24] than poor placebo adherers.”
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“It has been shown that better outcomes with treatment are closely associated to adherence to drug therapy, independent of the treatment administered [30].”
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“Given the reported strong patient preference for a monthly regimen, and the impact of patient preference on adherence, it is anticipated that monthly ibandronate will offer patients an alternative convenient regimen that may improve adherence over weekly regimens and thereby enhance outcomes.”
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Stuart, B., Davidoff, A. J., Lopert, R., Shaffer, T., Shoemaker, J. S., & Lloyd, J. L. E. (2011) · Health Services Research · doi:10.1111/j.1475-6773.2011.01250.x · Cited by 42
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Wampold, B. E. (2021) · Frontiers in Pain Research · doi:10.3389/fpain.2021.684768 · Cited by 45
“A meta-analysis of adherence to effective drug therapy and mortality found that the odds of mortality were lower when patients used their medications as directed, not surprisingly, but interestingly odds of mortality were also lower when patients adhered to a placebo as well, suggesting the benefits of adherence might…”
BackgroundFactors affecting medication adherence in Lebanese patients with chronic diseases
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“A meta-analysis of the relationship between adherence to placebo and total mortality in eight randomized clinical trials found that good adherence to the placebo was associated with a statistically significant 44% lower odds of death.(5) The basis for this lower risk is not known, and there is currently no sure way to…”
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“For example, previous studies have recognised a ‘‘healthy adherer’’ effect in which higher compliance with placebo was also associated with improved health outcomes [43].”
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“26 Inversely, nonadherence is very frequent in teenagers 27 and may simply represent one of the manifestations of disobedience that is a normal characteristic of this period of life, together with teenagers’ difficulty projecting themselves in the future.”
Bae, S. G., Kam, S., Park, K., Kim, K.-Y., Hong, N.-S., Kim, K.-S., Lee, Y., Lee, W. K., & Choe, M. S. P. (2016) · Patient Preference and Adherence · doi:10.2147/ppa.s114529 · Cited by 43
“Simpson et al 2 reported that patients with higher medication adherence showed lower mortality rate even in the placebo group.”
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“Non-adherence can diminish treatment effects leading to increased morbidity and mortality([4]) plus wasted healthcare resources.”
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“However, regardless of the specific disease, suboptimal medication adherence frequently results in negative health outcomes and increased morbidity and mortality.(4) In selected chronic conditions, such as HIV disease, suboptimal adherence can become a threat to public health as nonadherence to HIV medications can res…”
Küpper-Nybelen, J., Hellmich, M., Abbas, S., Ihle, P., Griebenow, R., & Schübert, I. (2012) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-012-1274-x · Cited by 40
“Adherent patients may be more likely to follow lifestyle recommendations, and take up preventive health services and other healthy behaviours leading to improved outcomes, an effect termed healthy user or healthy adherer bias in the literature [21, 37, 38].”
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“Evidence shows that non-adherence to medications results in higher health care costs, longer hospitalizations, and increased morbidity and mortality [6-8].”
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“PURPOSE Among patients on long-term medical therapy, we compared (1) patient and physician assessments of drug adherence and of drug importance and (2) drug adherence reported by patients with drug importance as assessed by their physicians.”
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Actividades preventivas en los mayores
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“32 Hence, multimorbidity associated with poor medication adherence has a significant negative impact on health, economic, and social SDGs that contribute to a significant burden on the person, public, and society.”
Changes in functional health, changes in medication beliefs, and medication adherence.
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“We have assumed that adherence is unrelated to risk. However, even with a placebo, poor adherence appears to be associated with increased risk of death,”
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“, 1994; Origasa, Yokoyama, Matsuzaki, Saito, & Matsuzawa, 2010) including reduced risk of mortality (Simpson et al., 2006).”
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“Evidence from placebo arms of clinical trials identify that better adherence to placebo reduces mortality [8, 9] and fracture risk [10].”
McKillop, G., & Joy, J. P. (2013) · Journal of Renal Care · doi:10.1111/j.1755-6686.2013.12037.x · Cited by 41
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BackgroundEffect of frailty syndrome on treatment compliance in older hypertensive patients
Chudiak, A., Jankowska‐Polańska, B., & Uchmanowicz, I. (2017) · Clinical Interventions in Aging · doi:10.2147/cia.s126526 · Cited by 37
Kubica, A., Kosobucka, A., Michalski, P., Fabiszak, T., & Felsmann, M. (2018) · Medical Research Journal · doi:10.5603/mrj.2017.0015 · Cited by 39
Patient-reported barriers to medication adherence in heart failure in Scotland
Forsyth, P., Richardson, J., & Lowrie, R. (2019) · International Journal of Pharmacy Practice · doi:10.1111/ijpp.12511 · Cited by 40
Accuracy of measures for antiretroviral adherence in people living with HIV
Smith, R., Villanueva, G., Probyn, K., Sguassero, Y., Ford, N. P., Orrell, C., Cohen, K., Chaplin, M., Leeflang, M., & Hine, P. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013080.pub2 · Cited by 39
Review: Predicting the probable outcome of treatment in HCV patients
Navaneethan, U., Kemmer, N. M., & Neff, G. W. (2009) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x09339079 · Cited by 37
“Poor adherence to treatment is an issue in diseases requiring long-term treatment, which results in poor health outcomes and increased health care costs hepatitis C is no exception to this [Simpson et al. 2006; Osterberg and Blaschke 2005].”
BackgroundCacoub, P., Ouzan, D., Melin, P., Lang, J.-P., Rotily, M., Fontanges, T., Varastet, M., Chousterman, M., & Marcellin, P. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.6195 · Cited by 37
“and that adherence, even to placebo, is essential to achieve health outcome goals [ 3 ]”
BackgroundCollaborative decision-making and promoting treatment adherence in pediatric chronic illness
Drotar, D. (2010) · Patient Intelligence · doi:10.2147/pi.s8820 · Cited by 37
Pharmacoadherence: A new term for a significant problem
Chisholm‐Burns, M. A., & Spivey, C. A. (2008) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp070372 · Cited by 42
LaFleur, J., Nelson, R. E., Sauer, B. C., & Nebeker, J. R. (2011) · Heart · doi:10.1136/hrt.2011.223289 · Cited by 37
“Perhaps the most compelling evidence of the healthy user effect comes from a meta-analysis showing decreased mortality in clinical trial patients who were adherent to placebo compared with those who were non-adherent to placebo.(26) In most studies, including adherence studies, healthy user bias is overlooked as a pot…”
BackgroundMedication Adherence and Incident Preventable Hospitalizations for Hypertension
Will, J. C., Zhang, Z., Ritchey, M. D., & Loustalot, F. V. (2015) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2015.08.021 · Cited by 35
Medication Adherence Among Recipients with Chronic Diseases Enrolled in a State Medicaid Program
Khanna, R., Pace, P. F., Mahabaleshwarkar, R., Basak, R., Datar, M. V., & Banahan, B. F. (2012) · Population Health Management · doi:10.1089/pop.2011.0069 · Cited by 36
Origasa, H., Yokoyama, M., Matsuzaki, M., Saitō, Y., Matsuzawa, Y., & The JELIS Investigators (2010) · Circulation Journal · doi:10.1253/circj.cj-09-0746 · Cited by 36
“Smoker 542 (21) 1,158 (17) 662 (21) 1,168 (19)”
InfluentialBlood pressure outcomes of medication adherence interventions: systematic review and meta-analysis
Conn, V. S., Ruppar, T. M., & Chase, J. D. (2016) · Journal of Behavioral Medicine · doi:10.1007/s10865-016-9730-1 · Cited by 37
“Poor medication adherence (henceforth, adherence) is a prevalent cause of inadequate hypertension control (Burnier, 2014; Christensen et al., 2009; De Geest et al., 2014; Erdine & Arslan, 2013; Simpson et al., 2006; Wofford & Minor, 2009).”
BackgroundKubica, A., Gruchała, M., Jaguszewski, M. J., Jankowski, P., Świeczkowski, D., Merks, P., & Uchmanowicz, I. (2018) · Medical Research Journal · doi:10.5603/mrj.2017.0016 · Cited by 36
Basnet, S., Zhang, M., LESSER, M. L., Wolf‐Klein, G. P., Qiu, G., Williams, M. S., Pekmezaris, R., & DiMarzio, P. (2018) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.13518 · Cited by 36
Ruksakulpiwat, S., Liu, Z., Yue, S., & Fan, Y. (2020) · Patient Preference and Adherence · doi:10.2147/ppa.s235107 · Cited by 37
Bergman, M. J., Patel, P., Chen, N., Jing, Y., & Saffore, C. D. (2020) · Rheumatology and Therapy · doi:10.1007/s40744-020-00256-x · Cited by 36
Shimony, A., Zahger, D., Ilia, R., Shaleṿ, A., & Cafri, C. (2009) · International Journal of Cardiology · doi:10.1016/j.ijcard.2009.04.033 · Cited by 36
Patil, S. P., Billings, M. E., Bourjeily, G. R., Collop, N. A., Gottlieb, D. J., Johnson, K. G., Kimoff, R. J., & Pack, A. I. (2023) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.10832 · Cited by 42
Drug treatment in an ageing population: Practical implications
Wynne, H., & Blagburn, J. (2010) · Maturitas · doi:10.1016/j.maturitas.2010.03.004 · Cited by 35
Nemes, M. I. B., Helena, E. T. D. S., Caraciolo, J. M. D. M., & Basso, C. R. (2009) · Cadernos de Saúde Pública · doi:10.1590/s0102-311x2009001500005 · Cited by 35
Evidence To Support Continuation of Statin Therapy in Patients with Staphylococcus aureus Bacteremia
Caffrey, A. R., Timbrook, T. T., Noh, E., Sakoulas, G., Opal, S. M., Nizet, V., & LaPlante, K. L. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02228-16 · Cited by 35
“Patients taking preventive medications, such as statins, are more likely to have healthier behaviors resulting in favorable outcomes, including lower mortality rates, than sicker patients (26, 27).”
BackgroundGathright, E. C., Dolansky, M. A., Gunstad, J., Redle, J. D., Josephson, R., Moore, S. M., & Hughes, J. W. (2017) · Health Psychology · doi:10.1037/hea0000529 · Cited by 35
“For example, medication nonadherence is often considered a marker of several unhealthy lifestyle behaviors associated with an increased risk of cardiac events and poor outcomes (Bonnet et al., 2005; Whooley, 2006; Simpson et al., 2006).”
Gerber, B., Cowling, T., Chen, G., Yeung, M., Duquette, P., & Haddad, P. (2017) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2017.10.001 · Cited by 35
Medication adherence among cardiac patients in Khartoum State, Sudan: a cross-sectional study
Awad, A. I., Osman, N., & Altayib, S. (2017) · Cardiovascular journal of South Africa/Cardiovascular journal of Southern Africa · doi:10.5830/cvja-2017-016 · Cited by 34
Adherencia terapéutica: factores modificadores y estrategias de mejora
Pagès‐Puigdemont, N., & Valverde-Merino, M. I. (2018) · Ars Pharmaceutica (Internet) · doi:10.30827/ars.v59i4.7357 · Cited by 35
“Asimismo, algunos estudios han demostrado que la falta de adherencia al tratamiento se correlaciona con un aumento de la mortalidad(7,8).”
BackgroundAntihypertensive Treatment in Elderly Frail Patients
Rea, F., Cantarutti, A., Merlino, L. G., Ungar, A., Corrao, G., & Mancia, G. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.14683 · Cited by 35
Jansà, M., Vidal, V., Giménez, M., Conget, Gallindo, M., Roca, Colungo, Esmatjes, & Salamero (2013) · Patient Preference and Adherence · doi:10.2147/ppa.s50271 · Cited by 38
Wilke, T., Müller, S., & Morisky, D. E. (2011) · Value in Health · doi:10.1016/j.jval.2011.06.002 · Cited by 35
“[7] Simpson SH, Eurich DT, Majumdar SR, et al.”
MethodWu, P., Johnson, B. A., Nachega, J. B., Wu, B., Ordóñez, C. E., Hare, A. Q., Kearns, R., Murphy, R. A., Sunpath, H., & Marconi, V. C. (2014) · Current HIV Research · doi:10.2174/1570162x1205141121102501 · Cited by 35
Burnier, M. (2014) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000045 · Cited by 34
Brewer, C. L., Streel, E., & Skinner, M. D. (2016) · Alcohol and Alcoholism · doi:10.1093/alcalc/agw093 · Cited by 36
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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