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Hypertension is a major cause of mortality in cardiac, vascular, and renal disease. Effective control of elevated blood pressure has been shown to reduce target organ damage. A Web-based self-titration program may empower patients to control their own disease, share decisions about antihypertensive dose titration, and improve self-management, ultimately improving health-related quality of life.
Our primary aim was to evaluate the effects of a Web-based self-titration program for improving blood pressure control in patients with primary hypertension. Our secondary aim was to evaluate the effects of that program on improving health-related quality of life.
This was a parallel-group, double-blind, randomized controlled trial with assessments at baseline, 3 months, and 6 months. We included patients with primary hypertension (blood pressure>130/80 mm Hg) from a cardiology outpatient department in northern Taiwan and divided them randomly into intervention and control groups. The intervention group received the Web-based self-titration program, while the control group received usual care. The random allocation was concealed from participants and outcome evaluators. Health-related quality of life was measured by the EuroQol five-dimension self-report questionnaire. We used generalized estimating equations to evaluate the effects of the intervention.
We included 222 patients and divided them equally into intervention (n=111) and control (n=111) groups. Patients receiving the Web-based self-titration program showed significantly greater improvement in the systolic and diastolic blood pressure control than those who did not receive this program, at 3 months (–21.4 mm Hg and –5.4 mm Hg, respectively;
A Web-based self-titration program can provide immediate feedback to patients about how to control their blood pressure and manage their disease at home. This program not only decreases mean blood pressure but also increases health-related quality of life in patients with primary hypertension.
ClinicalTrials.gov NCT03470974; https://clinicaltrials.gov/ct2/show/NCT03470974
The World Health Organization (WHO) reported that hypertension is one of the most common health concerns [
Hypertension is a major cause of mortality, resulting in 10.5 million deaths worldwide annually [
The poor adherence to health behaviors, a significant barrier to optimal blood pressure control [
In clinical practice, a cardiologist usually starts antihypertensive therapy by medication titration based on a patient’s response and educates patients about self-monitoring and self-adjustment of dosages at home [
Few randomized controlled trials have investigated the outcomes of medication titration on blood pressure control in patients with hypertension. The Telemonitoring and Self-Management in Hypertension 2 (TASMINH2) trial combined telemonitoring with a titration strategy to improve blood pressure control for patients with hypertension [
Nevertheless, two previous studies were unable to detect a significant finding of the effects of antihypertensive titration on blood pressure control [
We aimed to evaluate the effectiveness of a Web-based self-titration program on blood pressure control in patients with primary hypertension. Our primary hypothesis was that patients receiving the Web-based self-titration program in the intervention group would have a better control of SBP and DBP than the control group after 3 and 6 months. The secondary hypothesis was that the patients in the intervention group would show greater improvement in HRQoL than those in the control group.
This was a parallel-group, double-blind, randomized controlled trial. Participants were randomly assigned to an intervention group or a control group using a permuted block randomization design with a block size of 4. The random allocation was concealed from participants and outcome evaluators via the use of sequentially numbered opaque envelopes. Data were collected at baseline, 3 months, and 6 months. The study was based on the CONSORT-EHEALTH guidelines (V1.6) [
We enrolled patients with primary hypertension from a cardiovascular outpatient clinic of a medical center in northern Taiwan. The inclusion criteria were as follows: age of 20-79 years, diagnosis of primary hypertension with SBP≥130 mm Hg or DBP≥80 mm Hg, intake of less than four antihypertensive agents, access to a sphygmomanometer at home, ownership of a smart phone or personal computer to use, ability to read and understand Chinese or Taiwanese, and will to participate. The exclusion criteria were as follows: SBP≥180 mm Hg or DBP≥100 mm Hg; pregnancy; receipt of a heart transplant, permanent pacemaker, or implantable cardioverter defibrillator; diagnosis of arrhythmia, stroke, thyroid disease, major psychiatric disorder, renal disease, heart failure, acute myocardial infarction, cancer, or terminal disease; intake of antidepressants; or addiction to drugs or alcohol.
The study procedures were reviewed and approved by the Institutional Review Board (IRB 2-104-05-148) of the participating hospital. Before enrollment, the principal investigator explained the research purpose and procedures to the participants and obtained their written informed consent. The participants randomly assigned to the intervention group were trained to use the self-titration platform for 1 month and continuously received the self-titration intervention for 6 months. The participants in the control group received usual care.
The participants assigned to the intervention group received a 4-week training course before receiving the Web-based self-titration program. First, participants were given a secure account and a unique password of the website platform. We assisted participants with any set-up required on their smartphones or tablets. A stepwise instruction booklet was provided to guide log-in and use the platform. Second, the physicians of these participants set individualized blood pressure targets and explained the tailored medication titration instructions to each participant, who were then asked to rely on their home blood pressure recordings to titrate their medication doses. Third, participants were trained to measure their blood pressure by using automated electronic sphygmomanometers correctly. Finally, all participants received education about the management of hypertension.
When participants began the Web-based self-titration program, they were asked to measure their blood pressure before taking their medications and to report the data on the platform every day. We reviewed the data daily and provided a consultation through a phone call or website platform as needed for each individual participant. The physicians provided instructions to participants for any medication dosage change (increase or decrease), based on the self-monitoring data, through the website platform or clinical visit every month. The participants learned how to modify their lifestyle and manage hypertension by visiting the website repeatedly.
The participants in the control group received usual care, which included routine follow-up treatments for medication, lifestyle modification consultations, and a blood pressure check. Medications were adjusted depending on evaluations from their physicians at each clinical visit.
The principal investigator conducted a meeting to deal with problems arising in the study once a month. The outcomes were evaluated for both groups before starting the intervention and after initiating the intervention, at 3 months and 6 months.
Based on a review of the literature [
In the personal information section, we required patients to provide the following data: age, gender, education status, employment status, contact information, comorbidity, current medications, and next visit date. In the individual physical data section, we input hematology test data such as low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and serum creatinine levels through a chart review. Patients were able to access their blood test data through the website.
In the blood pressure recording section, we set up individual blood pressure targets for each patient. The patients measured their blood pressure and recorded the data through the Web. An alarm and reminder system was designed and set up to allow patients to clearly understand the meaning of their current blood pressure readings and how to deal with them (
In the patient education section, a video provided information about the management of hypertension and instructions about blood pressure measurements, a healthy diet, and exercise. The video content was designed based on the guidance of five experts from among the cardiologists and nurses. Finally, the patients were able to directly contact the research team through the consultation section.
Screenshot of instruction in self-titration strategy.
Screenshot of the medication reminder area and medication titration area.
Screenshot of curve diagram on blood pressure.
The following data were collected from self-reports and chart review before randomization: age, gender, education, marital status, occupation, smoking habits, body mass index, clinical history, antihypertensive medications, and duration of having hypertension. We calculated the antihypertensive dosage based on the defined daily dose (DDD), as recommended by the WHO, which uses assumed average maintenance doses per day for a drug according to its main indication in adults [
Blood pressure was measured with an automatic sphygmomanometer (JPN1; Omron Colin, Kyoto, Japan). According to the guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society, we asked the participants to sit in a quiet and comfortable room for at least 5 minutes before taking their blood pressure. The blood pressure was taken twice at intervals of 1-2 minutes [
We used the 3-level version of EuroQol five-dimension self-report questionnaire (EQ-5D-3L) [
We calculated the antihypertensive dosage based on the DDD, as recommended by the WHO, a unit of measurement for assumed average maintenance doses per day for a drug according to its main indication in adults. The DDD provides a standardized and objective dose unit, allowing clinicians or researchers to assess drug consumption dosage and compare patients with themselves or other patients. DDDs are only used for medicines after they are assigned Anatomical Therapeutic Chemical Classification System (ATC) codes [
The primary outcome was the mean SBP and DBP at 3 months and 6 months. The secondary outcomes were the overall antihypertensive DDD and the two measures for HRQoL at 3 months and 6 months.
We estimated the sample size using G*Power version 3.1 [
Data were analyzed by IBM SPSS, Version 21.0 (IBM Corp, Armonk, New York) based on intention-to-treat analysis. The analysis was conducted by a researcher who was blinded to the random allocation. The demographic and clinical characteristics were analyzed as means and SDs or as frequencies and percentages. Independent
Of the 356 enrolled patients, 18 did not meet the inclusion criteria and 116 (32.6%) declined to participate. Therefore, a total of 222 patients (62.4%) were included and randomly assigned to the intervention (n=111) or control (n=111) group.
The baseline characteristics of participants are summarized in
Flow diagram of the inclusion of patients in the randomized trial of the two groups.
We used GEE analysis to examine if there was an effect of the Web-based self-titration program on the control of SBP (
Generalized estimating equation analysis of the effect of the intervention on systolic blood pressure.
Variable | Regression coefficient | SE | χ2 (df) | |
Group (intervention)a | 0.12 | 1.86 | 0.004 (1) | .95 |
Time (3 mo)b | 5.28 | 1.36 | 15.2 (1) | <.001 |
Time (6 mo)b | 7.99 | 1.44 | 30.9 (1) | <.001 |
Group (intervention) × time (3 mo)c | –21.43 | 1.89 | 127.7 (1) | <.001 |
Group (intervention) × time (6 mo)c | –27.82 | 2.10 | 175.2 (1) | <.001 |
aReference group: control group.
bReference group: time (baseline).
cReference group: group (control) × time (baseline).
GEE analysis examined changes in DBP after controlling for the difference between groups at baseline. The mean DBP for the intervention group significantly decreased more at 3- and 6-month follow-ups (
Generalized estimating equation analysis of the effect of the intervention on diastolic blood pressure.
Variable | Regression coefficient | SE | χ2 (df) | |
Group (intervention)a | 0.536 | 1.44 | 0.1 (1) | .71 |
Time (3 mo)b | –1.586 | 0.83 | 3.6 (1) | .057 |
Time (6 mo)b | 0.477 | 1.03 | 0.2 (1) | .64 |
Group (intervention) × time (3 mo)c | –5.442 | 1.21 | 20.4 (1) | <.001 |
Group (intervention) × time (6 mo)c | –9.739 | 1.49 | 42.6 (1) | <.001 |
aReference group: control group.
bReference group: time (baseline).
cReference group: group (control) × time (baseline).
GEE analysis examined the effect of the Web-based self-titration program on changes in overall DDD for antihypertensive medicines. The GEE model, adjusted for the baseline difference between groups, showed that the mean DDD for the intervention group significantly decreased more than that for the control group (
Generalized estimating equation analysis of the effect of the intervention on overall defined daily dose.
Variable | Regression coefficient | SE | χ2 (df) | |
Group (intervention)a | –0.242 | 0.16 | 2.5 (1) | .12 |
Time (3 mo)b | 0.132 | 0.47 | 8.1 (1) | .004 |
Time (6 mo)b | 0.132 | 0.05 | 6.9 (1) | .008 |
Group (intervention) × time (3 mo)c | –0.202 | 0.07 | 8.9 (1) | .003 |
Group (intervention) × time (6 mo)c | –0.236 | 0.07 | 11.3 (1) | .001 |
aReference group: control group.
bReference group: time (baseline).
cReference group: group (control) × time (baseline).
GEE analysis of EQ-5D scores examined the effect of the Web-based self-titration program on improving HRQoL (
Generalized estimating equation analysis of the effect of the intervention on EuroQol five-dimension self-report questionnaire scores.
Variable | Regression coefficient | SE | χ2 (df) | |
Group (intervention)a | –0.074 | 0.02 | 17.5 (1) | <.001 |
Time (3 mo)b | –0.076 | 0.02 | 23.7 (1) | <.001 |
Time (6 mo)b | –0.108 | 0.02 | 40.7 (1) | <.001 |
Group (intervention) × time (3 mo)c | 0.216 | 0.02 | 113.1 (1) | <.001 |
Group (intervention) × time (6 mo)c | 0.275 | 0.02 | 171.6 (1) | <.001 |
aReference group: control group.
bReference group: time (baseline).
cReference group: group (control) × time (baseline).
The EQ-VAS used to measure participants’ self-rated health status was also evaluated at the 3- and 6-month follow-ups using the GEE model adjusted for the baseline difference between groups (
Generalized estimating equation analysis of the effect of the intervention on self-rated health status.
Variable | Regression coefficient | SE | χ2 (df) | |
Group (intervention)a | –11.247 | 1.89 | 35.5 (1) | <.001 |
Time (3 mo)b | –8.252 | 1.56 | 28.1 (1) | <.001 |
Time (6 mo)b | –12.820 | 1.65 | 60.5 (1) | <.001 |
Group (intervention) × time (3 mo)c | 24.459 | 1.92 | 163.0 (1) | <.001 |
Group (intervention) × time (6 mo)c | 36.883 | 2.08 | 314.4 (1) | <.001 |
aReference group: control group.
bReference group: time (baseline).
cReference group: group (control) × time (baseline).
This randomized clinical trial examined the effects of a web-based self-titration program on the control of blood pressure and HRQoL in patients with primary hypertension. The principal findings of this trial demonstrated that our Web-based self-titration program significantly improved blood pressure control, overall DDD for antihypertensive medicine, HRQoL, and self-rated health status at 3- and 6-month follow-ups compared to baseline measures. In addition, these improvements were significantly better than those seen in the control group at both follow-ups. Additionally, no harmful events occurred in our cohort.
Our results on the control of SBP and DBP are consistent with the findings of previous studies on the benefits of self-titration of antihypertensive medication for blood pressure control [
Another notable finding of our study was that the overall antihypertensive DDD was significantly reduced in the intervention group compared with the control group. No other studies have reported similar findings. The significant reduction in antihypertensive DDD for patients in the intervention group may have been a result of consultations and reminders from clinical professionals through the Web-based program. This support may have helped patients not only modify their lifestyle, but also persist in carrying out healthy behavior. Empowerment for lifestyle self-management and self-titration of their own medication has been shown to positively impact patient compliance [
HRQoL is frequently used to examine the beneficial effects of interventions and treatments [
Our results also showed that patients who engaged in the Web-based self-titration program perceived a significant improvement in their health status at the 3- and 6-month follow-ups. Health status is challenging to improve because it is a patient-centered outcome. The symptom burden significantly predicts worse health status [
The potential limitations in this study should be considered. First, our follow-up period was only 6 months, which meant that we could not detect the long-term consequences on cardiovascular events, or indeed, whether the initial successes would be sustainable in the long term. Nevertheless, the initial improvements in blood pressure control have a clear potential to reduce cardiovascular complication rates. Second, we used telemedicine to support the medication titration, which excluded patients without a computer or smartphone access. Third, we were not able to blind the patients’ physicians, which could have introduced bias. Finally, we only recruited participants from one medical center, which limits our ability to generalize the findings. These limitations should be addressed in future research.
There is limited research examining the effects of a Web-based self-titration program on blood pressure control in patients with primary hypertension. The results of this study support both our hypotheses: (1) patients with primary hypertension who received the Web-based self-titration program had significant control of SBP and DBP, and (2) the HRQoL of patients was significantly improved through this Web-based program. In addition, the intervention group had significant reductions in DDD for antihypertensive medications and improvements in the perception of their health status. Thus, we believe that the Web-based self-titration program may assist patients with primary hypertension to self-manage their treatments and healthy lifestyle in their home. This Web-based intervention program also has the benefit of reducing the amount of time required for patients to visit an outpatient clinic or hospital for care. Taken together, the intervention program could improve the quality of care for patients while reducing health care costs.
Alarm and Reminder system: Definitions of blood pressure readings and actions.
Demographic and clinical characteristics of participants and differences between groups.
Change in systolic blood pressure between two groups at 3 times.
Change in diastolic blood pressure between two groups at 3 times.
Change in the overall antihypertensive defined daily dose between two groups at 3 times.
Change in scores of EQ5D between two groups at 3 times.
Change in scores of ED-VAS between two groups at 3 times.
CONSORT‐EHEALTH checklist (V 1.6.1).
diastolic blood pressure
defined daily dose
3-level version of EuroQol five-dimension self-report questionnaire
EuroQol visual analogue scale
generalized estimating equation
health-related quality of life
systolic blood pressure
World Health Organization
This study was supported by a grant from the Ministry of Science and Technology, Taiwan (MOST 105-2314-B-016-029). We express our most sincere appreciation to all study participants.
None declared.