Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Adherence to antihypertensive medication and its predictors among non-elderly adults in Japan

Hypertension Research volume 43, pages 705–714 (2020)Cite this article

Abstract

Nonadherence to antihypertensive drugs is a primary reason for suboptimal clinical outcomes among hypertensive patients. We assessed adherence to newly initiated antihypertensive medications in non-elderly Japanese patients and examined which patient and facility characteristics were associated with low adherence. We selected new oral antihypertensive drug users, aged 30–74 years, between 2014 and 2016 from a large administrative claims database. We measured adherence as the proportion of days covered (PDC) during a 1-year follow-up and divided patients into three groups of low (PDC < 40%), intermediate (PDC ≥ 40% to <80%), and high (PDC ≥ 80%) adherence. Factors associated with low adherence were assessed by logistic regression analysis with generalized estimating equations. Among 31,592 patients (mean age, 51.7 years; 41.2% female), the median 1-year PDC was 88.5% (IQR: 41.9–98.1%). In total, 59.2%, 16.6%, and 24.2% of patients were categorized as having high, intermediate, and low adherence, respectively. Female sex (odds ratio [OR] 1.15, 95% confidential interval [95% CI] 1.08–1.22), younger age, and the initiation of angiotensin-converting enzyme inhibitors (OR 1.37, 95% CI 1.12–1.66), beta-blockers and thiazide diuretics (OR 4.82, 95% CI 4.34–5.36 and OR 3.91, 95% CI 2.79–5.46, respectively; compared with angiotensin II receptor blockers) were associated with low adherence. Patients initiating antihypertensives at larger hospitals (≥200 beds) were more likely to be adherent. While adherence to antihypertensive drugs in non-elderly Japanese patients was relatively high compared with that reported in previous studies in Western countries, patients with intermediate-low adherence may benefit from targeted interventions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. World Health Organization. Global action plan for the prevention and cntrol of noncommunicable disease 2013–2020. http://www.who.int/iris/handle/10665/94384. Accessed 12 June 2019.

  2. Esposti LD, Saragoni S, Benemei S, Batacchi P, Geppetti P, di Bari M, et al. Adherence to antihypertensive medications and health outcomes among newly treated hypertensive patients. Clin Outcomes Res. 2011;3:47–54. https://doi.org/10.2147/CEOR.S15619

    Article  Google Scholar 

  3. Yang Q, Chang A, Ritchey MD, Loustalot F. Antihypertensive medication adherence and risk of cardiovascular disease among older adults: a population-based cohort study. J Am Heart Assoc. 2017;6. https://doi.org/10.1161/JAHA.117.006056

  4. Tinetti ME, Han L, McAvay GJ, Lee DSH, Peduzzi P, Dodson JA, et al. Anti-hypertensive medications and cardiovascular events in older adults with multiple chronic conditions. PLoS ONE. 2014;9. https://doi.org/10.1371/journal.pone.0090733

  5. Kim S, Shin DW, Yun JM, Hwang Y, Park SK, Ko YJ, et al. Medication adherence and the risk of cardiovascular mortality and hospitalization among patients with newly prescribed antihypertensive medications. Hypertension. 2016;67:506–12. https://doi.org/10.1161/HYPERTENSIONAHA.115.06731

    Article  CAS  PubMed  Google Scholar 

  6. Lee HJ, Jang SI, Park EC. Effect of adherence to antihypertensive medication on stroke incidence in patients with hypertension: a population-based retrospective cohort study. BMJ Open. 2017;7:1–8. https://doi.org/10.1136/bmjopen-2016-014486

    Article  Google Scholar 

  7. Rodriguez F, Maron DJ, Knowles JW, Virani SS, Lin S, Heidenreich PA. Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiol. 2019;4:206–13. https://doi.org/10.1001/jamacardio.2018.4936

    Article  PubMed  PubMed Central  Google Scholar 

  8. Simard P, Presse N, Roy L, Dorais M, White-Guay B, Räkel A, et al. Association between metformin adherence and all-cause mortality among new users of metformin: a nested case-control study. Ann Pharmacother. 2018;52:305–13. https://doi.org/10.1177/1060028017743517

    Article  CAS  PubMed  Google Scholar 

  9. World Health Organization. Adherence to long-term therapies: evidence for action; 2015. https://www.who.int/chp/knowledge/publications/adherence_report/en/. Accessed 3 April 2019.

  10. Lam WY, Fresco P. Medication adherence measures: an overview. Biomed Res Int. 2015;2015:1–12. https://doi.org/10.1155/2015/217047

    Article  Google Scholar 

  11. Hamdidouche I, Jullien V, Boutouyrie P, Billaud E, Azizi M, Laurent S. Drug adherence in hypertension: Frommethodological issues to cardiovascular outcomes. J Hypertens. 2017;35:1133–44. https://doi.org/10.1097/HJH.0000000000001299

    Article  CAS  PubMed  Google Scholar 

  12. Osterberg L, Blaschke T. Adherence to medication dosage schedules. Control Clin Trials. 2005;10:333–4. https://doi.org/10.1016/0197-2456(89)90126-8

    Article  Google Scholar 

  13. Miura K, Nagai M, Ohkubo T. Epidemiology of hypertension in Japan. Circ J. 2013;77:2226–31. https://doi.org/10.1253/circj.CJ-13-0847

    Article  PubMed  Google Scholar 

  14. Mazzaglia G, Ambrosioni E, Alacqua M, Filippi A, Sessa E, Immordino V, et al. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation. 2009;120:1598–605. https://doi.org/10.1161/CIRCULATIONAHA.108.830299

    Article  CAS  PubMed  Google Scholar 

  15. Schulz M, Krueger K, Schuessel K, Friedland K, Laufs U, Mueller WE, et al. Medication adherence and persistence according to different antihypertensive drug classes: a retrospective cohort study of 255,500 patients. Int J Cardiol. 2016;220:668–76. https://doi.org/10.1016/j.ijcard.2016.06.263

    Article  PubMed  Google Scholar 

  16. Calderón-Larrañaga A, Diaz E, Poblador-Plou B, Gimeno-Feliu LA, Abad-Díez JM, Prados-Torres A. Non-adherence to antihypertensive medication: the role of mental and physical comorbidity. Int J Cardiol. 2016;207:310–6. https://doi.org/10.1016/j.ijcard.2016.01.069

    Article  PubMed  Google Scholar 

  17. Friedman O, McAlister FA, Yun L, Campbell NRC, Tu K. Antihypertensive drug persistence and compliance among newly treated elderly hypertensives in Ontario. Am J Med. 2010;123:173–81. https://doi.org/10.1016/j.amjmed.2009.08.008

    Article  PubMed  Google Scholar 

  18. Ishisaka DY, Jukes T, Romanelli RJ, Wong KS, Schiro TA. Disparities in adherence to and persistence with antihypertensive regimens: an exploratory analysis from a community-based provider network. J Am Soc Hypertens. 2012;6:201–9. https://doi.org/10.1016/j.jash.2012.02.004

    Article  PubMed  Google Scholar 

  19. Patel BV, Remigio-Baker RA, Mehta D, Thiebaud P, Frech-Tamas F, Preblick R. Effects of initial antihypertensive drug class on patient persistence and compliance in a usual-care setting in the United States. J Clin Hypertens. 2007;9:692–700. https://doi.org/10.1111/j.1524-6175.2007.07194.x

    Article  Google Scholar 

  20. Wong MCS, Tam WWS, Cheung CSK, Tong ELH, Sek ACH, Cheung NT, et al. Medication adherence to first-line antihypertensive drug class in a large Chinese population. Int J Cardiol. 2012;167:1438–42. https://doi.org/10.1016/j.ijcard.2012.04.060

    Article  PubMed  PubMed Central  Google Scholar 

  21. Liu KQL, Griffiths SM, Wong MCS, Kang CD, Wang HHX, Li WTL, et al. Determinants of medication adherence and blood pressure control among hypertensive patients in Hong Kong: a cross-sectional study. Int J Cardiol. 2014;182:250–7. https://doi.org/10.1016/j.ijcard.2014.12.064

    Article  PubMed  Google Scholar 

  22. Sakamoto H, Rahman M, Nomura S, Okamoto E, Koike S, Yasunaga H, et al. Japan health system review. World Health Organization. New Delhi, India: Regional Office for South-East Asia; 2018;8. p. 55.

  23. Pednekar PP, Ágh T, Malmenäs M, Raval AD, Bennett BM, Borah BJ, et al. Methods for measuring multiple medication adherence: a systematic review–Report of the ISPOR Medication Adherence and Persistence Special Interest Group. Value Heal. 2019;22:139–56. https://doi.org/10.1016/j.jval.2018.08.006

    Article  Google Scholar 

  24. Ho PM, Bryson CL, Rumsfeld JS. Medication adherence. Circulation. 2009;119:3028–35. https://doi.org/10.1161/CIRCULATIONAHA.108.768986

    Article  PubMed  Google Scholar 

  25. Kumamaru H, Lee MP, Choudhry NK, Dong Y-H, Krumme AA, Khan N, et al. Using previous medication adherence to predict future adherence. J Manag Care Spec Pharm. 2018;24:1146–55. https://doi.org/10.18553/jmcp.2018.24.11.1146

    Article  PubMed  Google Scholar 

  26. Ishida T, Oh A, Hiroi S, Shimasaki Y, Nishigaki N, Tsuchihashi T. Treatment patterns and adherence to antihypertensive combination therapies in Japan using a claims database. Hypertens Res. 2018;42:249–56. https://doi.org/10.1038/s41440-018-0127-0

    Article  CAS  PubMed  Google Scholar 

  27. Hanley JA, Negassa A, Edwardes MDdB, Forrester JE. Statistical analysis of correlated data using generalized estimating equations: an orientation. Am J Epidemiol. 2003;157:364–75. https://doi.org/10.1093/aje/kwf215

    Article  PubMed  Google Scholar 

  28. Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med. 2012;125:882–7.e1. https://doi.org/10.1016/j.amjmed.2011.12.013

    Article  PubMed  Google Scholar 

  29. Kurdi AI, Chen LC, Elliott RA. Exploring factors associated with patients’ adherence to antihypertensive drugs among people with primary hypertension in the United Kingdom. J Hypertens. 2017;35:1881–90. https://doi.org/10.1097/HJH.0000000000001382

    Article  CAS  PubMed  Google Scholar 

  30. Ho PM, Bryson CL, Rumsfeld JS. Medication adherence: its importance in cardiovascular outcomes. Circulation. 2009;119:3028–35. https://doi.org/10.1161/CIRCULATIONAHA.108.768986

    Article  PubMed  Google Scholar 

  31. Degli Esposti L, Esposti ED, Valpiani G, Di Martino M, Saragoni S, Buda S, et al. A retrospective, population-based analysis of persistence with antihypertensive drug therapy in primary care practice in Italy. Clin Ther. 2002;24:1347–57. https://doi.org/10.1016/S0149-2918(02)80039-X

    Article  PubMed  Google Scholar 

  32. Yang Z, Howard DH, Loustalot F, Ritchey M, Roy K, Will J. Association of antihypertensive medication adherence with healthcare use and medicaid expenditures for acute cardiovascular events. Med Care. 2016;54:504–11.

    Article  Google Scholar 

  33. Ferrario CM, Panjabi S, Buzinec P, Swindle JP. Clinical and economic outcomes associated with amlodipine/renin–angiotensin system blocker combinations. Ther Adv Cardiovasc Dis. 2013;7:27–39. https://doi.org/10.1177/1753944712470979

    Article  PubMed  Google Scholar 

  34. Elliott WJ, Plauschinat CA, Skrepnek GH, Gause D. Persistence, adherence, and risk of discontinuation associated with commonly prescribed antihypertensive drug monotherapies. J Am Board Fam Med. 2007;20:72–80. https://doi.org/10.3122/jabfm.2007.01.060094

    Article  PubMed  Google Scholar 

  35. Granger BB, Ekman I, Granger CB, Ostergren J, Olofsson B, Michelson E, et al. Adherence to medication according to sex and age in the CHARM programme. Eur J Heart Fail. 2009;11:1092–8. https://doi.org/10.1093/eurjhf/hfp142

    Article  PubMed  Google Scholar 

  36. Kim J, Lee E, Park BJ, Bang JH, Lee JY. Adherence to antiretroviral therapy and factors affecting low medication adherence among incident HIV-infected individuals during 2009-2016: a nationwide study. Sci Rep. 2018;8:1–8. https://doi.org/10.1038/s41598-018-21081-x

    Article  CAS  Google Scholar 

  37. Thunander Sundbom L, Bingefors K. Women and men report different behaviours in, and reasons for medication non-adherence: a nationwide Swedish survey. Pharm Pract. 2012;10:207–21.

    Article  Google Scholar 

  38. Ong L, Irvine J, Nolan R, Cribbie R, Harris L, Newman D, et al. Gender differences and quality of life in atrial fibrillation: the mediating role of depression. J Psychosom Res. 2006;61:769–74. https://doi.org/10.1016/j.jpsychores.2006.08.003

    Article  PubMed  Google Scholar 

  39. Kronish IM, Woodward M, Sergie Z, Ogedegbe G, Falzon L, Mann DM. Meta-Analysis. Circulation. 2011;123:1611–21. https://doi.org/10.1161/CIRCULATIONAHA.110.983874

    Article  PubMed  PubMed Central  Google Scholar 

  40. Mancia G, Soranna D, Rea F, Ghirardi A, Corrao G, Merlino L. Adherence with antihypertensive drug therapy and the risk of heart failure in clinical practice. Hypertension. 2015;66:742–9. https://doi.org/10.1161/hypertensionaha.115.05463

    Article  PubMed  Google Scholar 

  41. Ishida T, Oh A, Hiroi S, Shimasaki Y, Tsuchihashi T. Current prescription status of antihypertensive drugs in Japanese patients with hypertension: analysis by type of comorbidities. Clin Exp Hypertens. 2018;00:1–8. https://doi.org/10.1080/10641963.2018.1465074

    Article  Google Scholar 

  42. McDowell SE, Coleman JJ, Ferner RE. Systematic review and meta-analysis of ethnic differences in risks of adverse reactions to drugs used in cardiovascular medicine. Br Med J. 2006;332:1177–80. https://doi.org/10.1136/bmj.38803.528113.55

    Article  CAS  Google Scholar 

  43. NHS. Beta blockers—NHS. https://www.nhs.uk/conditions/beta-blockers/. Accessed 24 June 2019.

  44. Harvard Health Publishing. Tips for taking diuretic medications—Harvard Health. https://www.health.harvard.edu/heart-health/tips-for-taking-diuretic-medications. Accessed 24 June 2019.

  45. Raebel MA, Schmittdiel J, Karter AJ, Konieczny JL, Steiner JF. Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases. Med Care. 2013;51:S11–21. https://doi.org/10.1097/MLR.0b013e31829b1d2a

    Article  PubMed  PubMed Central  Google Scholar 

  46. Steiner JF, Prochazka AV. The assessment of refill compliance using pharmacy records: methods, validity, and applications. J Clin Epidemiol. 1997;50:105–16. https://doi.org/10.1016/S0895-4356(96)00268-5

    Article  CAS  PubMed  Google Scholar 

  47. Ohisa M, Kimura Y, Matsuo J, Akita T, Sato T, Matsuoka T, et al. Estimated numbers of patients with liver disease related to hepatitis B or C virus infection based on the database reconstructed from medical claims from 2008 to 2010 in Japan. Hepatol Res. 2015;45:1228–40. https://doi.org/10.1111/hepr.12497

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded, in part, by the Japan Agency for Medical Research and Development (grant number 17lk1010010h0002).

Author information

Authors and Affiliations

  1. Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo City, Tokyo, Japan

    Shiori Nishimura, Hiraku Kumamaru & Hiroaki Miyata

  2. Department of Health Policy and Management, Keio University School of Medicine, 35 Shinanomachi, Shinjuku City, Tokyo, Japan

    Shiori Nishimura & Hiroaki Miyata

  3. Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku City, Tokyo, Japan

    Satoshi Shoji, Mitsuaki Sawano & Shun Kohsaka

Authors
  1. Shiori Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiraku Kumamaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Satoshi Shoji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mitsuaki Sawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shun Kohsaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroaki Miyata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiraku Kumamaru.

Ethics declarations

Conflict of interest

HK, SK, and HM are affiliated with the Department of Healthcare Quality Assessment at the University of Tokyo. The department is a social collaboration department supported by the National Clinical Database, Johnson & Johnson K.K., and Nipro Corporation. SK reports investigator-initiated grant funding from Bayer and Daiichi Sankyo, and personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, Teikoku Seiyaku, and Boehringer Ingelheim, outside the submitted work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nishimura, S., Kumamaru, H., Shoji, S. et al. Adherence to antihypertensive medication and its predictors among non-elderly adults in Japan. Hypertens Res 43, 705–714 (2020). https://doi.org/10.1038/s41440-020-0440-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-020-0440-2

Keywords

This article is cited by

Search

Advanced search

Quick links