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Effects of combination drugs on antihypertensive medication adherence in a real-world setting: a Korean Nationwide Study
  1. Seung Jae Kim1,
  2. Oh Deog Kwon2,
  3. BeLong Cho3,
  4. Seung-Won Oh4,
  5. Cheol Min Lee4,
  6. Ho-Chun Choi4
  1. 1 Department of Family Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  2. 2 Navy Medical Office, ROK Submarine Force Command, Changwon, Korea
  3. 3 Department of Family Medicine, Seoul National University Hospital, Seoul, Korea
  4. 4 Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
  1. Correspondence to Dr Ho-Chun Choi; skyho331{at}


Objectives We tried to clarify, by using representative national data in a real-world setting, whether single-pill combinations (SPCs) of antihypertensives actually improve medication adherence.

Design A nationwide population-based study.

Setting We used a 2.2% cohort (n=1 048 061) of the total population (n=46 605 433) that was randomly extracted by National Health Insurance of Korea from 2008 to 2013.

Participants We included patients (n=116 677) who were prescribed with the same antihypertensive drugs for at least 1 year and divided them into groups of angiotensin II receptor blocker (ARB)-only, calcium channel blocker (CCB)-only, multiple-pill combinations (MPCs) and SPCs of ARB/CCB.

Primary outcome measures Medication possession ratio (MPR), a frequently used indirect measurement method of medication adherence.

Results Adjusted MPR was higher in combination therapy (89.7% in SPC, 87.2% in MPC) than monotherapy (81.6% in ARB, 79.7% in CCB), and MPR of SPC (89.7%, 95% CI 89.3 to 90.0) was higher than MPR of MPC (87.2%, 95% CI 86.7 to 87.7) (p<0.05). In subgroup analysis, adherence of SPC and MPC was 92.3% (95% CI 91.5 to 93.0) vs 88.1% (95% CI 87.1 to 89.0) in those aged 65–74 years and 89.3% (95% CI 88.0 to 90.7) vs 84.8% (95% CI 83.3 to 92.0) in those ≥75 years (p<0.05). According to total pill numbers, adherence of SPC and MPC was 90.9% (CI 89.8 to 92.0) vs 85.3% (95% CI 84.1 to 86.5) in seven to eight pills and 91.2% (95% CI 89.3 to 93.1) vs 82.5% (95% CI 80.6 to 84.4) in nine or more (p<0.05). The adherence difference between SPC and MPC started to increase at five to six pills and at age 50–64 years (p<0.05). When analysed according to elderly status, the adherence difference started to increase at three to four pills in the elderly (≥65 years) and at five to six in the non-elderly group (20–64 years) (p<0.05). These differences all widened further with increasing age and the total medications.

Conclusion SPC regimens demonstrated higher adherence than MPC, and this tendency is more pronounced with increasing age and the total number of medications.

  • hypertension
  • medication adherence
  • angiotensin li receptor blocker
  • calcium channel blocker
  • single pill combination

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  • Contributors SJK: conceived and designed the study, acquired and analysed the data, interpreted the study findings and drafted the manuscript. ODK: analysed the data and interpreted the study findings. S-WO, CML and BLC: critically reviewed the manuscript. H-CC: conceived and designed the study, supervised and directed the conduct of the study, interpreted the study findings and critically revised the manuscript; is the guarantor. All authors had full access to all of the data and the accuracy of the data analysis. The corresponding author attests that all listed authors meet authorship criteria and that no other meeting the criteria have been omitted.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Ethics approval This study was approved by the institutional review board (IRB) at the Seoul National University Hospital (IRB No.E-15-5-079-673) and National Health Insurance review committee for research support (NHIS-2017-2-610). Written informed consent was waived

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data are from the National Health Insurance service (NHIS). Interested researchers can request access to the data from NHIS. The detailed information for data access of NHIS could be obtained from the NHIS website (

  • Patient consent for publication Not required.

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