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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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“35 Cardiovascular disorders, % 6 (4) 2 (6) 0 (0) 2 (6) 2 (3) Pulmonary disorders, % 65 (43) 15 (45) 8 (36) 15 (43) 27 (44) Hepatobiliary disorders, % 7 (5) 0 (0) 3 (14) 3 (9) 1 (2) Gastrointestinal disorders, % 13 (9) 4 (12) 1 (5) 2 (6) 6 (10) Renal disorders, % 19 (13) 2 (6) 1 (5) 4 (11) 12 (19) Sepsis of other etiol…”
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“Healthier behaviour in general (‘healthy adherer effect’) may also be a contributing factor—indeed, non-adherence to placebo is associated with a twofold increase in mortality compared to placebo adherence.(17) Some estimates are more conservative— Eagle et al(18) reported lower discontinuation rates at 6 months (8% f…”
ResultOlder adults with difficulty swallowing oral medicines: a systematic review of the literature
Gillicuddy, A. M., Crean, A. M., & Sahm, L. J. (2015) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-015-1979-8 · Cited by 52
Busby, K. K., & Sajatovic, M. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00191.x · Cited by 57
“Furthermore, good adherence to drug therapy, in and of itself, is associated with positive health outcomes, namely lower mortality, in general medical populations, and it is postulated that adherence to drug therapy may serve as a marker for overall healthy behavior [21].”
BackgroundBerra, K. A. (2011) · The Journal of Cardiovascular Nursing · doi:10.1097/jcn.0b013e3181ec1337 · Cited by 51
Beer, L., Heffelfinger, J. D., Frazier, E. L., Mattson, C. L., Roter, B., Barash, E., Buskin, S. E., Rime, T. E., & Valverde, E. E. (2012) · The Open AIDS Journal · doi:10.2174/1874613601206010213 · Cited by 51
“Methods: We present interview data (collected from June 2007 through September 2008) from a national HIV surveillance system in the United States—the Medical Monitoring Project (MMP)—to describe persons taking ART.”
MethodDrug adherence in patients taking oral anticoagulation therapy
Ewen, S., Rettig‐Ewen, V., Mahfoud, F., Böhm, M., & Laufs, U. (2013) · Clinical Research in Cardiology · doi:10.1007/s00392-013-0616-8 · Cited by 49
Current and Emerging Pharmacologic Therapies for the Management of Postmenopausal Osteoporosis
Lewiecki, E. M. (2009) · Journal of Women s Health · doi:10.1089/jwh.2008.1086 · Cited by 49
Mody, R., Grabner, M., Yu, M. B., Turner, R., Kwan, A. Y. M., York, W., & Landó, L. F. (2017) · Current Medical Research and Opinion · doi:10.1080/03007995.2017.1421146 · Cited by 50
Brihi, J. E., Horne, R., & Faasse, K. (2018) · Annals of Behavioral Medicine · doi:10.1093/abm/kay011 · Cited by 53
Curtis, J. R., Delzell, E., Chen, L., Black, D. M., Ensrud, K. E., Judd, S. E., Safford, M. M., Schwartz, A. V., & Bauer, D. C. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.274 · Cited by 51
“importance of the healthy adherer effect come from several sources, including a meta-analysis of eight clinical trials showing that high compliance with placebo was associated with a 44% lower rate of death.((7)) High compliance also has been associated with health-seeking behavior, use of preventive services (eg, imm…”
BackgroundPaying for Outcomes: Innovative Coverage and Reimbursement Schemes for Pharmaceuticals
Carlson, J. J., Garrison, L. P., & Sullivan, S. D. (2009) · Journal of Managed Care Pharmacy · doi:10.18553/jmcp.2009.15.8.683 · Cited by 49
Infant Hospitalizations and Mortality After Maternal Vaccination
Sukumaran, L., McCarthy, N. L., Kharbanda, E. O., Vazquez‐Benitez, G., Lipkind, H. S., Jackson, L. A., Klein, N. P., Naleway, A. L., McClure, D. L., Hechter, R. C., et al. (2018) · PEDIATRICS · doi:10.1542/peds.2017-3310 · Cited by 51
Guerrero, A., Echeverría, J. J., & Tonetti, M. S. (2007) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2007.01130.x · Cited by 48
Rasmussen, L. D., Kronborg, G., Larsen, C. S., Pedersen, C., Gerstoft, J., & Obel, N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0052828 · Cited by 48
“Initiation of and adherence to statin therapy could therefore be a surrogate marker for a higher medical attention and a healthier lifestyle [40–42].”
BackgroundIssues in blood pressure control and the potential role of single-pill combination therapies
Burnier, M., Brown, R. E., Ong, S. H., Keskinaslan, A., & Khan, Z. M. (2009) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2009.01999.x · Cited by 48
Malá‐Ládová, K., Vlček, J., Vytrisalova, M., & Malý, J. (2013) · Journal of Evaluation in Clinical Practice · doi:10.1111/jep.12095 · Cited by 48
Donaho, E. K., Hall, A. C., Gass, J. A., Elayda, M. A., Lee, V., Pairé, S., & Meyers, D. E. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.115.002296 · Cited by 48
Stange, D., Kriston, L., von Wolff, A., Baehr, M., & Dartsch, D. C. (2013) · Journal of Managed Care Pharmacy · doi:10.18553/jmcp.2013.19.5.396 · Cited by 48
“Consistent adherence to cardiovascular and/or antidiabetic medication therapy, on the other hand, is associated with better healthrelated outcomes.(11,12)”
BackgroundAvataneo, V., Nicolò, A. D., Rabbia, F., Perlo, E., Burrello, J., Berra, E., Pappaccogli, M., Cusato, J., D’Avolio, A., Perri, G. D., et al. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13706 · Cited by 48
Kengne, A. P., Brière, J., Zhu, L., Li, J., Bhatia, M. K., Atanasov, P., & Khan, Z. M. (2023) · Expert Review of Pharmacoeconomics & Outcomes Research · doi:10.1080/14737167.2023.2266135 · Cited by 55
Berben, L., Bogert, L., Leventhal, M., Fridlund, B., Jaarsma, T., Norekvål, T. M., Smith, K. M., Strömberg, A., Thompson, D. R., & Geest, S. D. (2010) · European Journal of Cardiovascular Nursing · doi:10.1016/j.ejcnurse.2010.10.004 · Cited by 47
de Thurah, A. L., Nørgaard, M., Johansen, M. B., & Stengaard‐Pedersen, K. (2010) · Scandinavian Journal of Rheumatology · doi:10.3109/03009740903251318 · Cited by 47
Sidorkiewicz, S., Tran, V.-T., Cousyn, C., Perrodeau, É., & Ravaud, P. (2016) · BMJ Open · doi:10.1136/bmjopen-2015-010510 · Cited by 47
“3 This situation may lead to increased hospitalisation rates and long-term mortality.(4) 5 Clinicians and researchers need tools to detect medication non-adherence.”
BackgroundHealth locus of control: Its relationship with medication adherence and medication wastage
West, L. M., Theuma, R. B., & Cordina, M. (2017) · Research in Social and Administrative Pharmacy · doi:10.1016/j.sapharm.2017.12.003 · Cited by 47
Chisholm‐Burns, M. A., Kwong, W. J., Mulloy, L. L., & Spivey, C. A. (2008) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp070630 · Cited by 47
“, azathioprine, mycophenolate mofetil), only cyclosporine and tacrolimus were used to calculate adherence rates because (1) either cyclosporine or tacrolimus is prescribed as the base immunosuppressant therapy for most renal transplant recipients and (2) monitoring adherence to several immunosuppressant agents would i…”
BackgroundLamb, D. A., Eurich, D. T., McAlister, F. A., Tsuyuki, R. T., Semchuk, W., Wilson, T. W., & Blackburn, D. F. (2009) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.108.813600 · Cited by 48
Self-citationThe process of medication management for older adults with dementia
Kaasalainen, S., Dolovich, L., Παπαϊωάννου, Α., Holbrook, A. M., Lau, E., Ploeg, J., Levine, M., Cosby, J., & Emili, A. (2011) · Journal of Nursing and Healthcare of Chronic Illness · doi:10.1111/j.1752-9824.2011.01114.x · Cited by 46
Abdull, M. M., Chandler, C., & Gilbert, C. E. (2016) · BMC Ophthalmology · doi:10.1186/s12886-016-0220-6 · Cited by 46
“Studies from around the world have identified the problem of low adherence or drop out from glaucoma treatment [16–19], being associated with poor knowledge of glaucoma [20–24], low levels of education [25, 26], black ethnicity [12, 27–31], worsening visual field loss [32], increasing age [28, 33, 34], lack of access…”
BackgroundAnsmann, L., & Pfaff, H. (2017) · International Journal of Health Policy and Management · doi:10.15171/ijhpm.2017.95 · Cited by 46
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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