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Comparison of therapy persistence for fixed versus free combination antihypertensives: a retrospective cohort study
  1. Thomas Grimmsmann1,2,
  2. Wolfgang Himmel3
  1. 1German Health Insurance Medical Service (MDK) Mecklenburg-Vorpommern, Schwerin, Germany
  2. 2Department of General Practice, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
  3. 3Department of General Practice, University Medical Center, Göttingen, Germany
  1. Correspondence to Professor Wolfgang Himmel; whimmel{at}


Objectives The aim of the study was to compare therapy persistence among patients who started with one of three drug regimens: a monotherapy, or combination therapy either as a fixed combination (ie, ‘single pill’) or as a free combination (ie, two separate antihypertensive agents).

Design In a secondary data analysis, we used descriptive statistics and multivariate logistic regression to measure the effect of the three therapy regimens on therapy persistence over 4 years.

Setting Prescription data from a large German statutory health insurance provider.

Participants All patients who started with a new antihypertensive therapy in 2007 or 2008 (n=8032) were included and followed for 4 years.

Primary outcome measure Therapy persistence, defined as receiving a refill prescription no later than within 180 days.

Results The persistence rates after 4 years were nearly identical among patients who started with a monotherapy (40.3%) or a fixed combination of two drugs (39.8%). However, significantly more patients who started with free-drug combinations remained therapy persistent (56.4%), resulting in an OR of 2.00 (95% CI 1.6 to 2.5; p<0.0001) for free combinations versus fixed combinations. This trend was observed in all age groups and for men and women. At the end of the study period, the number of different antihypertensive agents was still similar between patients who started with a fixed combination (2.41) and patients who started with a free combination (2.28).

Conclusions While single-pill combinations make it easier to take different drugs at once, the risk is high that these several substances are stopped at once. Therapy persistence was significantly better for patients who started with a free-drug combination without taking much fewer different antihypertensive drugs as those with a fixed combination.

  • Drug adherence
  • Drug utilization review
  • Drug combinations
  • Patient compliance
  • Primary health care

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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  • Prior presentations: Preliminary results were presented at the 20th Annual Meeting of the German Drug Utilisation Research Group (GAA), December 2013, Düsseldorf, Germany.

  • Contributors TG and WH designed the study, performed the statistical analyses, supervised all aspects of the study, wrote the manuscript, critically reviewed and revised the manuscript, approved the final manuscript as submitted and are the guarantors. TG was responsible for the management and retrieval of data.

  • Competing interests None declared.

  • Ethics approval Ethical approval was not necessary owing to the nature of the data (secondary data analysis of anonymised files).

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

  • Data sharing statement No additional data are available.

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