Use of Directly Observed Therapy to Assess Treatment Adherence in Patients With Apparent Treatment-Resistant Hypertension | Hypertension | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Table 1.  Baseline Characteristics of the Study Participantsa
Baseline Characteristics of the Study Participantsa
Table 2.  Change in Daytime Systolic Blood Pressure
Change in Daytime Systolic Blood Pressure
1.
Burnier  M, Wuerzner  G, Struijker-Boudier  H, Urquhart  J.  Measuring, analyzing, and managing drug adherence in resistant hypertension.  Hypertension. 2013;62(2):218-225. doi:10.1161/HYPERTENSIONAHA.113.00687PubMedGoogle ScholarCrossref
2.
Fadl Elmula  FE, Hoffmann  P, Larstorp  AC,  et al.  Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.  Hypertension. 2014;63(5):991-999. doi:10.1161/HYPERTENSIONAHA.114.03246PubMedGoogle ScholarCrossref
3.
Ruzicka  M, Hiremath  S.  Can drugs work in patients who do not take them? the problem of non-adherence in resistant hypertension.  Curr Hypertens Rep. 2015;17(9):579. doi:10.1007/s11906-015-0579-4PubMedGoogle ScholarCrossref
4.
Ruzicka  M, McCormick  B, Leenen  FH, Froeschl  M, Hiremath  S.  Adherence to blood pressure-lowering drugs and resistant hypertension: should trial of direct observation therapy be part of preassessment for renal denervation?  Can J Cardiol. 2013;29(12):1741.e1-1741.e3. doi:10.1016/j.cjca.2013.07.678PubMedGoogle ScholarCrossref
5.
Brinker  S, Pandey  A, Ayers  C,  et al.  Therapeutic drug monitoring facilitates blood pressure control in resistant hypertension.  J Am Coll Cardiol. 2014;63(8):834-835. doi:10.1016/j.jacc.2013.10.067PubMedGoogle ScholarCrossref
6.
Eskås  PA, Heimark  S, Eek Mariampillai  J, Larstorp  AC, Fadl Elmula  FE, Høieggen  A.  Adherence to medication and drug monitoring in apparent treatment-resistant hypertension.  Blood Press. 2016;25(4):199-205. doi:10.3109/08037051.2015.1121706PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    Use of Directly Observed Therapy to Assess Treatment Adherence in Patients With Apparent Treatment-Resistant Hypertension
    hana morrissey, PhD | University of Wolverhampton
    Dear Editor

    1. The authors are to be congratulated on finding one effective intervention for non-adherence in hypertension which is widely known to be a huge problem. We would take issue however with the opening statement about limited tests for non-adherence. All are effective tools for demonstrating non-adherence, but all the best studies use a combination of checks and clinical reviews/measurements As the authors recognise, the challenge is then to address the non-adherence.
    2. Refill data and pill counts do only demonstrate non-adherence and are open to manipulation by the patient to give a false impression. What steps were taken
    to verify the accuracy of pill count.
    3. We believe the Morisky Widget provides more useful data because non-adherence is not unidimensional. It occurs for a variety of reasons intentional and non-intentional. Detecting a person non-adherent not only allows targeting of interventions but also their knowledge of their non-adherence start the adherence change process, to self-defend or because of their understanding improved or self-responsibility due to the feeling of being part of the problem; the person’s behaviour become ready to be altered or their intention to change is already in the preparation stage to change behaviour.
    4. What are the questions that were asked to determine if the patient was adherent or not? What was the environment where patients were questioned? inpatient, outpatient, resident in an institution or living at home?
    5. The conduct of this study appears to remove self-care responsibility from the patient and force the patient to re-learn new behaviour of adherence (compliance) which is good but not sustainable considering the prevalence of hypertension is very high globally. We believe video DOT in collaboration with Morisky Widget would produce better more sustainable outcomes as the reason of nonadherence can be detected and managed while the new behaviour is developed and observed by practitioners including outside of business hours.
    6. Using the prison system of pill parade where prisoners take most of their treatment as DOT, the health outcome after release remarkably reduced usually due to under recognised or poorly managed patients poor self-care behaviour, understanding of the treatment mechanism of action in relation to the condition and complication with cognitive/learning disability/mental illness and disorders.

    Thanks
    Dr Hana Morrissey
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Research Letter
    Less Is More
    June 17, 2019

    Use of Directly Observed Therapy to Assess Treatment Adherence in Patients With Apparent Treatment-Resistant Hypertension

    Author Affiliations
    • 1Renal Hypertension Center, Division of Nephrology, University of Ottawa, Ottawa, Ontario, Canada
    • 2Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
    • 3Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
    • 4Kidney Research Center, University of Ottawa, Ottawa, Ontario, Canada
    JAMA Intern Med. 2019;179(10):1433-1434. doi:10.1001/jamainternmed.2019.1455

    Among patients with apparent treatment-resistant hypertension,1-3 nonadherence to treatment is common. Pharmacy refill data, the Morisky scale, and pill counts are limited tests for determination of nonadherence. In this study, we aimed to assess the contribution of nonadherence to blood pressure (BP)–lowering drugs undetected by these tests by evaluating the association of directly observed therapy (DOT) with treatment adherence in patients with apparent treatment-resistant hypertension.

    Methods

    This prospective observational cohort study was performed at a specialized hypertension center and was approved by the Ottawa Health Sciences Research Ethics Research Board. Adults (aged >18 years) with apparent treatment-resistant hypertension, defined as daytime mean systolic BP of 135 mm Hg or greater on 24-hour ambulatory blood pressure monitoring (ABPM) (SpaceLabs Healthcare), who were receiving 3 or more BP-lowering drugs were eligible. Adherence to prescribed BP-lowering drugs was assessed before enrollment with use of standard questioning by a hypertension clinic nurse, review of pharmacy filling records for the past 6 months, and pill count. Only patients for whom there was complete concordance with pharmacy records, pill count, and treatment regimen were enrolled. Patients who provided written consent underwent DOT, with a 1 month follow-up.4 On the day of DOT, prescribed BP-lowering drugs were administered by a nurse, and the BP response was monitored until peak BP effect was reached. A 24-hour ABPM was performed immediately after the peak effect of treatment was reached and again at 1 month. The primary outcome was the proportion of participants with daytime mean systolic BP less than 135 mm Hg on 24-hour ABPM after DOT, and the secondary outcome was this proportion at 1 month.

    Results

    A total of 60 consecutive patients (32 men [67%]; mean [SD] age, 62.1 [13.1] years) were enrolled in the study, and after exclusion of those who withdrew consent (n = 4), did not attend DOT (n = 4), or missed subsequent ABPM (n = 4), 48 participants completed this study for the primary outcome and 46 for the secondary outcome. Baseline characteristics are reported in Table 1. After DOT, daytime systolic BP remained 135 mm Hg or greater in 34 of 48 patients (71%) who experienced a mean (SD) decrease in systolic BP of 3 (10) mm Hg. In contrast, in 14 participants (29%), treatment-resistant hypertension resolved and systolic BP decreased by 26 (20) mm Hg (Table 2). This proportion was similar at 1 month in 14 of 46 patients (30%) who no longer had treatment-resistant hypertension.

    Discussion

    The results suggest that nonadherence to BP-lowering drug regimens is high among referred patients with apparent treatment-resistant hypertension, even among those who said they were adherent on questioning before DOT, had pristine pharmacy filling records, and had accurate pill counts. Moreover, this apparent nonadherence occurred despite more than 50% of these patients already having had an adverse vascular event related to uncontrolled hypertension. However, we cannot exclude the possibility that the process of being in the study or receiving treatment from a nurse in a clinic was associated with lower BP for some patients. Of interest, most of those with markedly improved BP after DOT had a sustained improvement in BP control seen at 1 month. Limitations of the study include that the patients were highly selected and likely do not represent most patients with hypertension in the community. The use of DOT as described here was strictly dichotomous (adherence vs nonadherence) and thus does not allow for precise assessment of the degree of nonadherence (eg, partial vs complete), as may be the case with therapeutic drug monitoring.5,6 Overall, the findings suggest that rigorous methods of adherence assessment and intervention such as DOT should be considered for patients with apparent treatment-resistant hypertension.

    Back to top
    Article Information

    Accepted for Publication: March 29, 2019.

    Corresponding Author: Marcel Ruzicka, MD, PhD, FRCPC, Renal Hypertension Center, Division of Nephrology, University of Ottawa, 1967 Riverside, Rm 5-21, Ottawa, Ontario K1H 7W9, Canada (mruzicka@ottawahospital.on.ca).

    Published Online: June 17, 2019. doi:10.1001/jamainternmed.2019.1455

    Author Contributions: Drs Ruzicka and Hiremath had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Ruzicka, Ramsay, McCormick, Hiremath.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Ruzicka, Leenen, Ramsay, Hiremath.

    Critical revision of the manuscript for important intellectual content: Ruzicka, Ramsay, Bugeja, Edwards, McCormick, Hiremath.

    Statistical analysis: Ruzicka, Ramsay, Hiremath.

    Obtained funding: Ruzicka, Ramsay, Hiremath.

    Administrative, technical, or material support: Ruzicka, Leenen, Ramsay, McCormick, Hiremath.

    Supervision: Ruzicka, Ramsay, Bugeja, Edwards, McCormick, Hiremath.

    Conflict of Interest Disclosures: Dr Ruzicka reported receiving grants from Physicians Services Incorporated and The Ottawa Hospital Academic Medical Organization–Innovation Fund Provincial Oversight Committee during the conduct of the study. Dr Hiremath reported receiving grants from the Canadian Institutes of Health Research, Physicians Services Incorporated, and The Ottawa Hospital Academic Medical Organization outside the submitted work. No other disclosures were reported.

    Funding/Support: This study was funded by a peer-reviewed grant (Dr Ruzicka) provided by The Ottawa Hospital Academic Medical Organization and the Innovation Fund Provincial Oversight Committee (Ontario, Canada).

    Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: Peter Magner, MD, FRCPC, provided critical review of the concept and results of this study (not compensated); Valerie Cronin, RN, was the research coordinator for the study (compensated); and the Hypertension Clinic study staff conducted the direct observed therapy procedures (compensated).

    References
    1.
    Burnier  M, Wuerzner  G, Struijker-Boudier  H, Urquhart  J.  Measuring, analyzing, and managing drug adherence in resistant hypertension.  Hypertension. 2013;62(2):218-225. doi:10.1161/HYPERTENSIONAHA.113.00687PubMedGoogle ScholarCrossref
    2.
    Fadl Elmula  FE, Hoffmann  P, Larstorp  AC,  et al.  Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.  Hypertension. 2014;63(5):991-999. doi:10.1161/HYPERTENSIONAHA.114.03246PubMedGoogle ScholarCrossref
    3.
    Ruzicka  M, Hiremath  S.  Can drugs work in patients who do not take them? the problem of non-adherence in resistant hypertension.  Curr Hypertens Rep. 2015;17(9):579. doi:10.1007/s11906-015-0579-4PubMedGoogle ScholarCrossref
    4.
    Ruzicka  M, McCormick  B, Leenen  FH, Froeschl  M, Hiremath  S.  Adherence to blood pressure-lowering drugs and resistant hypertension: should trial of direct observation therapy be part of preassessment for renal denervation?  Can J Cardiol. 2013;29(12):1741.e1-1741.e3. doi:10.1016/j.cjca.2013.07.678PubMedGoogle ScholarCrossref
    5.
    Brinker  S, Pandey  A, Ayers  C,  et al.  Therapeutic drug monitoring facilitates blood pressure control in resistant hypertension.  J Am Coll Cardiol. 2014;63(8):834-835. doi:10.1016/j.jacc.2013.10.067PubMedGoogle ScholarCrossref
    6.
    Eskås  PA, Heimark  S, Eek Mariampillai  J, Larstorp  AC, Fadl Elmula  FE, Høieggen  A.  Adherence to medication and drug monitoring in apparent treatment-resistant hypertension.  Blood Press. 2016;25(4):199-205. doi:10.3109/08037051.2015.1121706PubMedGoogle ScholarCrossref
    ×