Abstract
This cohort study evaluates the association of directly observed therapy with treatment adherencee in patients with apparent treatment-resistant hypertension.
Among patients with apparent treatment-resistant hypertension,1,2,3 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.
Table 1. Baseline Characteristics of the Study Participantsa.
| Characteristic | Patients (n = 48) |
|---|---|
| Men | 32 (66.7) |
| Age, mean (SD), y | 62.1 (13.1) |
| BMI, mean (SD) | 32.3 (6.0) |
| Daytime ABPM, mean (SD), mm Hg | |
| Systolic | 153.5 (13.2) |
| Diastolic | 80.9 (14.0) |
| Comorbidities | |
| History of coronary artery disease | 21 (44) |
| History of stroke or TIA | 5 (11) |
| History of diabetes | 22 (46) |
| Treatment for dyslipidemia | 29 (62) |
| Active smoking | 0 |
| Drug coverage | |
| Provincial insurance | 43 (90) |
| Private drug plan | 32 (67) |
| No drug coverage | 3 (6) |
| Antihypertensive medications | |
| No. of BP-lowering drugs, median (range) | 4 (3-7) |
| Calcium channel blockersb | 44 (92) |
| Renin angiotensin system blockersc | 42 (87) |
| Thiazide or thiazide-like diuretics | 36 (75) |
| Mineralocorticosteroid antagonist or potassium-sparing diuretics | 33 (69) |
| β-Adrenergic antagonists | 31 (65) |
| α-Adrenergic antagonists | 14 (29) |
| Loop diuretics | 4 (8) |
| Others | |
| Clonidine | 4 (8) |
| Minoxidil | 2 (4) |
| Hydralazine | 1 (2) |
| Alpha-methyldopa | 2 (4) |
Abbreviations: ABPM, ambulatory blood pressure monitoring; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); BP, blood pressure; TIA, transient ischemic attack.
Data are presented as number (percentage) of patients unless otherwise indcated.
One patient was receiving dihydropyridine and a nondihydropyridine calcium channel blocker.
One patient was receiving an angiotensin converting enzyme inhibitor and an angiotensin-receptor blocker.
Table 2. Change in Daytime Systolic Blood Pressure.
| Time Point | Mean (SD), mm Hg | ||
|---|---|---|---|
| Overall | With Daytime ABPM Mean Value | ||
| SBP <135 mm Hg | SBP ≥135 mm Hg | ||
| Immediately after DOT (n = 48) | −9.7 (17.3) | −26.1 (19.9) | −2.9 (10.4) |
| 1 mo After DOT (n = 46) | −11.0 (15.8) | −21.9 (14.0) | −6.3 (14.2) |
Abbreviations: ABPM, ambulatory blood pressure monitoring; DOT, directly observed therapy; SBP, systolic blood pressure.
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.
References
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