Study design and participants
This study was a prospective single-group interventional study and was approved by the Institutional Review Board of the Seoul National University Hospital (No. H-1902–132-1015). Patients were recruited from a cardiology clinic in Seoul National University Hospital, a tertiary academic medical center in Republic of Korea. Patients were eligible for inclusion if their cardiologist judged them to be appropriate candidates for this study, their BP had been controlled in normotensive range (< 140/90 mmHg) for at least 6 months with a single tablet dose of antihypertensive medication; the value of their 24-h ambulatory BP monitoring within 1 month before the study enrollment was 135/85 mmHg or below; they were between 20 to 60 years old. Patients with secondary hypertension, cardiovascular complications (e.g., myocardial infarction), or renal dysfunction were excluded.
Outcome
The outcome of this study was the success rate of antihypertensive medication withdrawal, which was assessed from the cumulative time-related curve over 6 months. If patients met one or more of the following criteria, they were considered unsuccessful in discontinuing their antihypertensive medications, and were categorized in the hypertensive group: (1) office systolic BP of 140 mmHg above or diastolic BP of 90 mmHg above on two consecutive visits, (2) office systolic BP of 160 mmHg above or diastolic BP of 100 mmHg above on any one visit, or (3) resumed antihypertensive medication.
Blood pressure measurement
The automated office BP readings were obtained based on standard procedures. The first BP readings were obtained in both arms, and then patients were instructed to use the arm with a higher BP monitoring throughout the study. Patients had a series of three BP readings at least 2 minutes apart after resting for at least 5 minutes. A mean of three consecutive automated office BP readings was recorded.
Factors related to the success of antihypertensive medication discontinuation
Adherence to self-care activities for hypertension
Adherence to self-care activities for hypertension is based on the behavior subdomain of the Hypertension Self-Care Profile Behavior Scale [14]. The behavior subdomain consists of 20 items related to recommended lifestyle modifications (e.g., low fat and low sodium diet, exercise, smoking cessation, and stress management), taking medications as directed, and attending all clinic appointments. Each item is rated on a 1 to 4 Likert scale, and total scores can range from 20 to 80, with higher scores indicating better adherence to self-care activities. Because two items related to taking medications were irrelevant for this study, we used the remaining 18 items, with the total scores ranging from 18 to 72. The psychometric validity of the Korean version was supported [15].
Health literacy
Health literacy was measured with the Newest Vital Sign [16]. Patients are asked six questions about the "nutrition facts" label from a pint of ice cream. The number of correct responses is summed to produce a total score ranging from 0 to 6. Scores below four indicate limited to possibly limited health literacy.
Depressive symptoms
The nine-item Patient Health Questionnaire was used to measure the levels of depressive symptoms [17]. Patients were asked to rate their depressed moods over 2 weeks on a 4-point Likert scale (0–3). The sum of each item yields a total score, with higher scores indicating higher levels of depressive symptoms. A total score of 10 or greater indicates clinically significant depressive symptoms [17]. The validity of the Korean version was supported in a previous study [18].
Anxiety
The anxiety subscale of the Brief Symptom Inventory-18 was used to measure anxiety [19]. This subscale consists of six items based on a 5-point Likert scale (0–4). Total scores were the average of the scores of the six items, with higher scores indicating a higher level of anxiety. The psychometric soundness of the Korean version of the Brief Symptom Inventory-18 was supported in a previous study [20].
Sociodemographic information
Sociodemographic information (e.g., age, family history of hypertension) was obtained based on self-report. Height and weight were measured by trained research nurses using the standard clinical procedures (e.g., removing heavy clothes and shoes). Body mass index was calculated by weight in kilograms divided by height in meters. A medical record review for each participant was performed to collect the laboratory data (e.g., lipid panel).
Study procedures
After obtaining ethical approval from the Institutional Review Board at the study site, eligible patients were referred to the researchers by their cardiologists. A written signed informed consent was obtained from each patient who received a thorough explanation of the study and voluntarily agreed to participate.
At baseline, automated office BP was taken using the standard procedure, and patients completed the questionnaires (e.g., sociodemographic information and health literacy). They also received verbal education, a booklet highlighting the importance of home BP monitoring at least twice daily, and recommended lifestyle modifications. They were also provided a contact number. Patients were instructed to stop their BP medications after the baseline data collection of this study, which was informed to their cardiologist.
Patients were followed up 1, 3, and 6 months after the baseline. Three automated office BP readings were taken. They also completed the questionnaire about their adherence to self-care activities for hypertension at each visit. Reasons for withdrawal from the study were also collected.
After the 6-month follow-up, participants were invited to participate in a semistructured, in-depth interview to elicit information about their experience with antihypertensive drug discontinuation (e.g., what changes did you make after drug discontinuation?). The interviews were conducted in person in a private space and lasted 20 to 50 min. Audio-recorded interviews were transcribed verbatim. The transcribed interviews were summarized to describe the experience of discontinuing antihypertensive medications and the reasons for withdrawal from the study, if applicable. Six patients participated in the interviews; two in the normotensive group, two in the hypertensive group, and two who withdrew from the study.
Statistical analyses
To describe the success rate of antihypertensive medication discontinuation over 6 months, we used the Kaplan–Meier curve of time to have elevated office BP based on the preset criteria (i.e., above 140/90 mmHg on two consecutive visits, above 160/100 mmHg on any time visit, or physicians’ prescription for antihypertensive medications). The survival probability was summarized at 1, 3, and 6 months. The linear mixed model with repeated measures was used to compare changes in office BP readings over 6 months between the normotensive and hypertensive groups. Time was introduced as the repeated effect, and a compound symmetry covariance matrix handled dependencies in the data. Explanatory factors included the two BP status groups (normotensive and hypertensive groups), time, and the interaction between the BP status groups and time.
To compare the sample characteristics between the normotensive and hypertensive groups, the Mann–Whitney U-test (an alternative nonparametric test to an independent t-test), chi-square test, or Fisher exact test was used as appropriate. The linear mixed model with repeated measures was used to compare changes in adherence to self-care activities for hypertension over 6 months. In addition to comparing the characteristics between patients who dropped out of the study and those who did not, the Mann–Whitney U-test, chi-square test, or Fisher exact test was used as appropriate. A P-value of ≤ 0.10 was considered statistically significant for all analyses because of the study's exploratory nature. Statistical analyses were performed using SAS ver. 9.4 (SAS Institute Inc., Cary, NC, USA).