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Ruzicka M, Leenen FHH, Ramsay T, et al. Use of Directly Observed Therapy to Assess Treatment Adherence in Patients With Apparent Treatment-Resistant Hypertension. 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.
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.
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.
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.
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 (firstname.lastname@example.org).
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).