Evaluation of the Effect of a Mobile Phone Application on Treatment Success and Drug Adherence in Hypertensive Patients

Evaluation of the Effect of a Mo bile Phone Application on Treatment Suc cess and Drug Adherence in Hypertensive Patients. One of the most important factors affecting the prognosis of hypertension is the patients’ adherence to drug therapy. In this study, it was aimed to evaluate the improvement in drug adherence in hypertensive patients after using a mobile phone application. Patients and Methods: In this single-centered study fifty patients with hypertension were recruited. All the patients used the Medisafe® mobile phone application for 8 weeks. The application is intended to increase drug adherence of patients and provide better blood pressure control. The differences in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels from the baseline and the levels at the end of the study were compared. The drug adherence was evaluated using the 8-question Morisky Drug Adherence Scale (MMAS-8) at baseline and at the end of the study. Results: The mobile application utilization provided a significant decrease in both the mean SBP levels by 6.2 mmHg (p<0,001) and in the mean DBP levels by 2.4 mmHg (p=0.035) Additionally, the mobile application also positively and significantly increased the drug adherence of the patients (mean baseline score: 5.54 vs mean end of the study score:6.3 and p=0,001). In the subgroup analysis of the study demonstrated that in addition to an increase in patients drug adherence, the use of the mobile application provided a significant decrease in the mean SBP levels by 6.6 mmHg(p=0.016) in geriatric patients but the decrease in DBP did not significantly change (p>0.05). In geriatric patients, the mean difference between drug adherence scores baseline and after application was found to be significant (p=0.006). With the use of mobile application, patients with polypharmacy had decreased mean SBP and DBP levels, and an increased mean MMAS-8 score of 5.07 to 5.85 (p=0.009). The present pilot study demonstrated that mobile application use in patients with hypertension may increase the treatment success and the patients drug adherence. The beneficial effects of mobile applications in the treatment of hypertension and other common chronic diseases should be evaluated in further larger clinical trials.


Introduction
Hypertension is one of the leading causes of cardiovascular mortality and morbidity and the prevalence increasing with age.
Uncontrolled hypertension is highly associated with cardiovascular and cerebrovascular diseases including myocardial infarction heart failure, stroke, and dementia [1]. It is estimated that the prevalence of hypertension in patients above 60 years of age is approximately 60% [2]. One of the main adversities concerning the control of hypertension is the inappropriate use of drugs. Drug adherence is about 50% in hypertension patients according to the literature.
Adherence is the adaptation of a person to lifestyle changes, diet, and medication given by the healthcare professional [3]. The level of compliance with the drug treatment is called drug adherence. A low level of drug adherence is one of the important challenges for the management of chronic diseases. Sociodemographic factors such as age, gender, and education levels contribute to drug adherence.
It was shown that the complications of chronic diseases are more frequently observed in elderly patients who have low drug adherence [4]. It is a fact that the drug adherence is not at a satisfactory level globally [5]. A poorly organized healthcare system, poor access to medication and inability to provide a rapid recovery from drugs especially in chronic diseases, and a lack of information about the disease may lower drug adherence. On the other hand, if good communication between patients and physician is maintained, drug adherence increases. Therefore, patient involvement in the management of chronic diseases should not be ignored. There is a need to increase the awareness and the involvement of patients in the treatment to improve drug adherence.
The widespread use of new approaches and technological tools may provide an opportunity. In hypertensive patients, a high level of drug adherence is important to maintain optimal levels of blood pressure and to prevent complications.
One of the main reasons for drug-resistant hypertension is the lack of drug adherence and it is shown that only 50% of hypertensive patients take the prescribed drugs appropriately [6]. In cases where higher drug adherence levels are achieved, it is stated that risk of stroke is reduced by 35-40% and the risk of myocardial infarction is reduced by 20-25% [7,8]. In recent years the use of mobile applications in the treatment of chronic diseases such as hypertension has increased considerably. More than 100 mobile applications for hypertension are available from different sources. In studies in which the effect of mobile phone applications on hypertension were evaluated, it has been shown that the use of applications increased patient-physician coordination, increased patient's awareness of hypertension, and ensured the patient take more responsibility for their hypertension [9,10]. The Morisky Medication Drug Adherence Scale-8(MMAS-8) is a survey including eight questions that are commonly used to evaluate drug adherence rates in hypertensive patients. It is shown that MMAS-8 is a useful tool for detecting low drug adherence in hypertensive patients [11].
In this study, we aimed to investigate the change of drug adherence rates in hypertensive patients after the use of mobile phone applications for the management of hypertension.

Study Population
Fifty patients with hypertension who were age≥18 and under treatment with anti-hypertensive medication for at least three months and presented to Istanbul Medical Faculty Department of Clinical Pharmacology Polyclinic were included in this study.

Blood Pressure Measurement
Blood pressure measurements were taken after resting for a minimum of 5 minutes in a sitting position, measured using a clinical-trial-use approved, validated, and calibrated oscillatory blood pressure measurement device (Omron 7051T, Kyoto, Japan).
The patients did not take caffeinated drinks or smoked cigarettes 30 minutes before measurement. Two measurements were taken in 5-minute intervals and blood pressure levels were recorded as the average of those 2 measurements. Blood pressure measurements were done in office conditions at the beginning and at the end of 8 weeks. The baseline blood pressure and the blood pressure after

Evaluation of Drug Adherence
Blood pressure measurements were done and patients were asked questions from MMAS-8. According to the answers, patients were classified as low adherers, medium adherers, and high adherers. Patients who scored less than 6 points were categorized as low adherers, patients who scored between 6-8 points were categorized as medium adherers and patients who scored 8 points were categorized as high adherers according to the MMAS-8 scale [11]. After the questionnaire, the Medisafe® program which is a free application available at the Apple Store and Google Play Store had been downloaded on the mobile phones of the patients. The Medisafe® application was chosen because it has an easy interface to use, and it is available for free. The name of the medication, the medication administering time had already been recorded into the Medisafe® program by the physician. After eight weeks, blood pressure measurements were taken and drug adherence rates were assessed by MMAS-8 scale.

Statistical Analysis
Statistical analyses were performed using IBM's Statistical Package for the Social Sciences (SPSS) Windows version 21.0. The distribution of variables was tested using the Shapiro-Wilk test.
For variables with normal distribution, paired t-test and Pearson correlation analyses were performed. For variables without normal distribution, the Wilcoxon Signed rank and Spearman's rho correlation analysis were conducted. Pearson's Chi-square test was used to examine the differences between categorical variables. The results were considered significant if p<0.05.

Drug Adherence
The drug adherence of patients was evaluated with MMAS-8.
The MMAS-8 score average was found to be 6.3. After application twenty-two patients' drug adherence rates were improved. The change in MMAS-8 scores at baseline and after application was found significant (p<0,001). In patients with polypharmacy, nine patients were found low adherent (%64%) and five patients were found medium adherent (36%). In non-polypharmacy patients, sixteen patients were found low adherent (44%), fifteen patients were found medium adherent (42%) and five patients were found high adherent (14%).

Opinion of Patients about Application
After the use of the application for 8 weeks, patients were asked two questions to assess their opinions about the application.
The first question patients were asked was whether they thought the application made it easier for them to take their medication. There are other studies on chronic diseases using mobile phone applications. The effect of mobile phone application use on hypertensive patients was evaluated, the results concluding that the use of mobile phone application did not provide an improvement in SBP but increased the drug adherence [12].
In a study on patients with heart failure, a mobile phone application was used to record the health data of these patients, and the information was shared with the patients' physicians [13].
Thus, it was aimed to increase the awareness of patients about heart failure and to decrease hospitalization. In another study carried out on hypertensive patients, the blood pressure values and drug adherence of the patients were evaluated after using a mobile phone application, and a significant decrease in blood pressure values and an increase in drug adherence were found [8]. In our study, we mainly evaluated the blood pressure and drug adherence rates of patients at baseline and after application use. The decrease in SBP after the use of mobile phone applications was found statistically significant (p<0.001). The decrease in DBP was found less significant (p=0.035). It was stated that an average decrease of 10 mmHg in SBP and an average decrease of 5 mmHg in DBP, reduces morbidity and mortality by preventing cardiovascular and cerebrovascular diseases [14,15]. Considering this evidence, the use of application would be valuable in preventing cardiovascular and cerebrovascular morbidity and mortality.
After application use, the overall MMAS-8 score average and patients drug adherence rates were increased. The rise in the MMAS-8 score average was found statistically significant after application use (p=0.001). Recent studies also showed that mobile phone applications that provide drug reminders and help patients to record their health data regularly, increase drug adherence especially in patients with chronic diseases and using multiple drugs [16,17]. It was shown that an increasing number of drugs may reduce the drug adherence of patients [18,19]. In our study, patients taking four or more medications a day were polypharmacy patients.
The MMAS-8 score of non-polypharmacy patients compared to polypharmacy patients was found higher and statistically significant (p=0.015). The decrease in SBP values of polypharmacy patients before and after application use was found to be significantly lower (p=0.045). The decrease in DBP was not found to be statistically significant (p>0.05). The increase in the MMAS-8 score of polypharmacy patients after mobile phone application was found significant (p=0.009)

Conclusion
The use of mobile phone application increased drug adherence rates and maintained better control of blood pressure. In order to reach a more definite conclusion there is need for further clinical studies on larger groups of patients evaluating the benefit of mobile phone applications on drug adherence and blood pressure. In parallel to technologic improvement the use of remote monitoring systems with more detailed features will provide better control for the patients and should be encouraged.

Limitations
The results of this present study may support beneficial effects of mobile phone application use. The present pilot study had a relatively small sample size and did not have a control group. The results of this study are beneficial to the design further larger clinical studies. Further larger clinical studies including control groups should be performed to reach a definitive conclusion