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Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories

BMJ 2008; 336 doi: (Published 15 May 2008) Cite this as: BMJ 2008;336:1114
  1. Bernard Vrijens, chief scientist and adjunct professor of biostatistics12,
  2. Gäbor Vincze, principal health economist 3,
  3. Paulus Kristanto, senior biostatistician 1,
  4. John Urquhart, professor of biopharmaceutical sciences 4,
  5. Michel Burnier, professor of nephrology5
  1. 1Pharmionic Research Center, Rue des Cyclistes Frontière 24, 4600 Visé, Belgium
  2. 2University of Liège, Department of Biostatistics and Medical Informatics, Liège, Belgium
  3. 3Novartis Pharma, Basel, Switzerland
  4. 4University of California at San Francisco, Center for Drug Development Science, San Francisco, USA
  5. 5University Hospital of Lausanne, Division of Nephrology and Hypertension Consultation, Lausanne, Switzerland
  1. Correspondence to: B Vrijens bernard.vrijens{at}
  • Accepted 14 April 2008


Objective To describe characteristics of dosing history in patients prescribed a once a day antihypertensive medication.

Design Longitudinal database study.

Setting Clinical studies archived in database for 1989-2006.

Participants Patients who participated in the studies whose dosing histories were available through electronic monitoring.

Main outcome measures Persistence with prescribed antihypertensive treatment and execution of their once a day drug dosing regimens.

Results The database contained dosing histories of 4783 patients with hypertension. The data came from 21 phase IV clinical studies, with lengths ranging from 30 to 330 days and involving 43 different antihypertensive drugs, including angiotensin II receptor blockers (n=2088), calcium channel blockers (n=937), angiotensin converting enzyme inhibitors (n=665), β blockers (n=195), and diuretics (n=155). About half of the patients who were prescribed an antihypertensive drug had stopped taking it within one year. On any day, patients who were still engaged with the drug dosing regimen omitted about 10% of the scheduled doses: 42% of these omissions were of a single day’s dose, whereas 43% were part of a sequence of several days (three or more days—that is, drug “holidays”). Almost half of the patients had at least one drug holiday a year. The likelihood that a patient would discontinue treatment early was inversely related to the quality of his or her daily execution of the dosing regimen.

Conclusions Early discontinuation of treatment and suboptimal daily execution of the prescribed regimens are the most common facets of poor adherence with once a day antihypertensive drug treatments. The shortfalls in drug exposure that these dosing errors create might be a common cause of low rates of blood pressure control and high variability in responses to prescribed antihypertensive drugs.


  • Contributors: BV conceived and designed the study, prepared the first draft, and is guarantor. BV and PK acquired and analysed the data. All authors participated in interpreting the results of the analysis. All authors reviewed and drafted the subsequent versions of the manuscript.

  • Funding: Novartis Pharma, Switzerland.

  • Competing interests: JU is a shareholder of Aardex, the company that manufactures the MEMS monitors.

  • Ethical approval: Not required.

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

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