Introduction  

Hypertension is the cause of the death of 7.5 million people worldwide. The prevalence of hypertension is reported to increase in the range of 35-46% in developing and developed countries and is predicted to increase by 60% by 2025. Increased prevalence will result in the risk of stroke (60%) and heart attack (50%). The hypertension morbidity rate in the United States is 27.8, while in Indonesia the mortality rate due to hypertension and heart disease is quite high, which is around 28% ^[1].

Hypertension is defined as an increase in systolic blood pressure, diastolic blood pressure or both ^[2]. The clinical diagnosis of hypertension is based on an average of two or more sitting blood pressure readings at every two or more regular visits ^{[3, 4]}. The goal of antihypertensive therapy is to reduce the risk of cardiovascular and renal morbidity and mortality ^[5]. The target reduction in systolic and diastolic blood pressure is <140/90 mmHg (in non-diabetic patients) associated with a reduction in cardiovascular complications ^[6]. For hypertensive patients with diabetes or chronic kidney disease, the target of lowering blood pressure is lower, namely 130/80 mmHg. Antihypertensive treatment is generally for a lifetime. A treatment that is stopped sooner or later will be followed by a rise in blood pressure until it reaches the previous rate when antihypertensive treatment has just begun. However, it is possible to gradually reduce the dosage and amount of antihypertensive drugs for patients whose diagnosis of hypertension is certain and remains compliant with non-pharmacological treatment.

This action must be accompanied by strict blood pressure monitoring ^[7]. According to data from the World Health Organization (WHO), of as many as 50% of hypertensive patients in developing countries, only 25% received treatment and only 12.5% ​​were treated properly. Also, there are 50–70% of patients who are not compliant with prescribed antihypertensive drugs. The average compliance of patients on long-term treatment of chronic diseases in developed countries is only 50%, while in developing countries the possibility is much lower. Low patient adherence to hypertension treatment has the potential to be a barrier in achieving controlled blood pressure and can also be associated with an increase in the cost of treatment or hospitalization and complications of heart disease ^[8]. Healthy people for hypertension recommend the need for a more comprehensive and intensive approach to achieve optimal blood pressure control. Efforts are needed in increasing patient compliance with drug therapy to achieve the desired blood pressure target. At least 50% of patients prescribed antihypertensive drugs do not take the drugs as recommended. The most effective strategy is a combination of strategies such as education, attitude modification, and supporting systems ^[9].

Counseling to patients conducted by Pharmacists is a component of pharmaceutical services aimed at increasing therapeutic outcomes by maximizing the use of drugs appropriately ^[10]. Thus, patients can feel the benefits by improving the quality of life and quality of health services. The essence of counseling is to help people deal effectively with important issues or issues.

Patient compliance in taking medication or medication adherence is defined as the level of obedience of patients to follow the recommended treatment given. Compliance with taking medication is very important especially for patients with chronic diseases. Adherence to taking medication can be influenced by demographic factors, patient factors, therapeutic factors and the relationship of patients with health care workers. One indicator of patient compliance with antihypertensive medication is blood pressure control ^[11].

According to the Pharmaceutical Services Standard at the Primary healthcare centers, the Pharmacist's work at the Primary Healthcare Centers includes counseling and providing drug information (PIO, PelayananInformasiObat) to patients in need ^[12]. Proven through counseling, Pharmacists can identify and overcome drug-related problems, empower patients to implement positive self-behavior management, increase patient satisfaction and can optimize the quality of patient care. Effective counseling will make patients understand the disease and treatment that is being undertaken and improve medication adherence ^[13]. A study shows that chronic disease patients with long-term therapy that adhere to treatment instructions are estimated at only 30-50% ^[14]. A mistake that often occurs is if the complaint disappears, the patient feels healed, then is not compliant in taking medication ^[15].

Pandeglang Regency was previously designated as a disadvantaged area through Presidential Regulation (Perpres, Peraturan Presiden) Number 131 of 2015 concerning the Determination of Underdeveloped Regions in 2015-2019 ^[16]. Based on observations and data obtained from the Pandeglang District Health Office, the total number of Primary Healthcare Centers in the Pandeglang Regency are 36 Primary Primary Healthcare Centers. When this research was conducted, not all Primary Healthcare Centers were Pharmacists, so 16 Primary Healthcare Centers were used as research objects, with 16 Pharmacists, located in 16 sub-districts in the Pandeglang Regency. Also, research on the influence of antihypertensive drug counseling on hypertension patients' compliance and blood pressure at the Pandeglang District Health Center has never been done. Based on this background, this research was conducted.

Subjects and Method

The study uses an experimental research method with a static group comparison design. The purpose of this study was to determine the effect of antihypertensive drug counseling on adherence and clinical outcome of prolanic hypertension patients in 8 Primary Healthcare Centers by pharmacists who had received counseling training. This study uses a control group that is the delivery of drugs without giving drug counseling by the Pharmacist (Pharmacists only submit drug information). Drug counseling conducted by the Pharmacist includes in-depth explanation related to the name of the drug, time of use, duration of use, how to use it, effects that will arise, and other things that will arise, as well as identifying problems and finding solutions to problems in the use of antihypertensive drugs. Also given an explanation of non-pharmacological therapy (about diet, lifestyle, and physical activity).

The research instrument used was the patient's medical record/prescription drug data from the doctor to find out the results of the doctor's diagnosis that the patient had hypertension, know the patient's identity, and the drug is given to the patient, and the MARS (Medication Adherence Report Scale) questionnaire to determine the compliance of hypertensive patients in taking antihypertensive drugs. In this study, the independent variables were drug counseling and the dependent variable was Systolic Blood Pressure (SBP) and hypertension patient compliance levels in 16 Primary Healthcare Centers in Pandeglang District in June-August 2019 period. Also, there were confounding variables, namely frequency of drug use, history of hypertension, just experienced or has long experienced patient education, and patient character. The population in this study were patients who seek treatment and redeem prescriptions at 16 Primary Healthcare Centers in Pandeglang district in the period June-August 2019. Sampling was done purposively. The samples used in this study were patients diagnosed with hypertension by doctors by looking at medical record data, getting antihypertensive drugs by doctors, redeeming prescription drugs at Primary Healthcare Centers and those who met the inclusion and exclusion criteria.

1. Inclusion Criteria

1. Complicated hypertension patients receiving antihypertensive drugs in 16 Primary

Healthcare Center Pandeglang Regency

2. Patients aged ≥18 years.
3. Hypertensive patients funded by BPJS Health.
4. Patients have medical record data
5. Patients who have made at least four visits to the Primary Healthcare Centers with a minimum of on times experiencing blood pressure above normal and receive counseling services from Pharmacist.

2. Exclusion Criteria

1. The patient is undergoing hemodialysis
2. The patient is an obstetric-gynecology patient
3. Patients in one consecutive period of four months did not visit the Primary Healthcare Centers.

Data collection for hypertensive patients is carried out in June-August 2019. Data taken includes the patient's name, age, address, no. phone/cell, sex, occupation, and antihypertensive drugs used. Hypertension patient compliance data obtained through the MARS questionnaire at each meeting for 4 times, after receiving the drug and giving drug counseling by interview. The recapitulated data was then tested with KruskalWalis, Mann-Whitney, Wilcoxon, and Binomial Tests. The effect of the p-value is then compared with an error rate (α) of 5% or 0.05. If p-value ≤ 0.05, then Ho is rejected and H1 is accepted, meaning that there is a significant relationship between the dependent variable and the independent variable. If p value> 0.005, then Ho is accepted and H1 is rejected, meaning that there is no significant relationship between the dependent variable and the independent variable. This study hypothesizes that drug counseling can significantly influence the compliance of hypertensive patients and the blood pressure reduction of hypertension patients at 16 Primary Healthcare Centers in Pandeglang District in the period June-August 2019.

Result

This research was carried out throughout 3 (three) months from June to August 2019 and was conducted prospectively of hypertensive patients who participated in the BPJS PROLANIS group. Subjects who followed the study from beginning to end were 96 patients, consisting of 48 hypertensive patients who did not receive counseling from Pharmacists in 8 Primary Healthcare Centers (control groups) and 48 hypertensive patients who received treatment in the form of counseling from Pharmacists who had received counseling training (groups treatment) at 8 Primary Healthcare Centers. Sampling was carried out by the inclusion criteria and the Pharmacist's ability to provide counseling and monitor patient progress until the 4th meeting. Monitoring the level of therapeutic outcomes (blood pressure) and the level of adherence in patients carried out for 2 (two) months. Sociodemographic data consists of age, gender, and occupation. This data was obtained from the patient's medical record/prescription drug data from the doctor. The sociodemographic frequency distribution of respondents can be seen in table 1.

Source: Data processing researchers from the results of medical records and interviews

1. Age

Based on the results of research, the lowest age of hypertension is 36 years old and the highest age is 70 years old. The age is then classified based on age classification according to the Indonesian Ministry of Health (2009) ^[17] with an age range of 40-82 years. Based on the frequency distribution, those aged> 65 years who are included in the elderly group have the highest frequency of experiencing hypertension, which is 37%. After the age of 45 years, the artery walls will experience thickening due to the accumulation of collagen in the muscle layer, so that the blood vessels will gradually narrow and become stiff. Systolic blood pressure increases because the flexibility of large blood vessels decreases with age until the seventh decade while diastolic blood pressure rises until the fifth and sixth decades and then settles or tends to decrease. Increased age will cause some physiological changes, in the elderly, there is an increase in peripheral resistance and sympathetic activity. The regulation of blood pressure, namely reflex baroreceptors in old age, has decreased sensitivity, while the role of the kidneys has also been reduced where renal blood flow and glomerular filtration rates have decreased ^[17].

2. Gender

Based on gender, it was shown that women had more hypertension, 77 people (80%) than men, 19 people (20%). Based on the theory that up to the age of 55 years, men are at higher risk than women, but women above that age have a greater chance ^[18]. Women who have not experienced menopause are protected by the hormone estrogen which plays a role in increasing levels of High-Density Lipoprotein (HDL). High levels of HDL are protective factors in preventing the process of atherosclerosis. The protective effect of estrogen is thought to be an explanation of a woman's immunity at premenopausal age. Premenopausal women begin to lose little by little the hormone estrogen which has been protecting blood vessels from damage. This process continues where the hormone estrogen changes in quantity according to a woman's natural age, which generally begins to occur in women aged 45-55 years ^[17].

3. Job

Based on the job shows that the level of hypertension is higher in housewives, namely 51 people (53%). This is in line with research which states that respondents who do not work have a 1.42 times risk of developing hypertension because work is related to psychological effects on the work environment ^[19]. The psychological influence experienced can be in the form of stressful events. This is following the theory which states that stress can increase peripheral blood vessels and cardiac output so that it will stimulate sympathetic nerve activity ^[17]. In the use of antihypertension, the drugs used do not only consist of a single antihypertension but some are also composed of two drugs antihypertension. Single antihypertension (85%) is more widely prescribed than antihypertensive drugs (15%). This is following the research from Norman (2012) ^[20] and Saepudin, et al (2013) ^[21], which obtained the results that most respondents received a single antihypertensive drug.

Antihypertensive Drugs

Antihypertensives which are often prescribed singly consist of amlodipine, captopril, and bisoprolol. The most commonly used drugs for single antihypertensive use are amlodipine 5 mg (P1 = 50.98%, P2 = 55.92%, P3 = 63.54% and P4 = 57.73%). Based on the use of antihypertensive drugs, the drugs used are amlodipine and captopril. This is not the same as the research from Norman (2012) and Saepudin, et al (2013) which obtained the results that the most widely used antihypertensive drugs both single and antihypertensive drugs are hydrochlorothiazides. The differences that occur in the use of drugs for hypertensive patients can be caused by the pathophysiological conditions of illness in each different patient. So that treatment aims to overcome other health problems besides hypertension and to support the treatment of hypertension. The use of antihypertensive drugs more than two drugs is done to increase the antihypertensive effect and reduce side effects. The use of amlodipine, captopril, and bisoprolol drugs are the guidelines for the Formulary Primary Healthcare Centers published by the Pandeglang District Health Office and the treatment of hypertension therapy for the Ministry of Health of the Republic of Indonesia.

Effects of Pharmacist Counseling on Adherence

Distribution of Patient Compliance in this study an assessment of patient compliance was obtained based on the results of the MARS questionnaire. Patients were divided into two groups, namely without giving counseling and Pharmacist counseling. The purpose of the grouping is to determine the effect of counseling from pharmacists on patient compliance in taking anti-hypertensive drugs and on their clinical impact, namely systolic blood pressure. The MARS questionnaire contains 5 questions containing answers always, often, sometimes, rarely and never with a total MARS score of 25. Compliance is said to be high if the MARS score obtained is 25. If the MARS score obtained is 6-24 then it includes moderate compliance. If the MARS score obtained is less than 6 then it is considered low compliance. The MARS questionnaire that has been validated by Dyah Perwitasari, et al (2015) ^[22] can be seen in table 2. Based on the results of the MARS questionnaire from the 1st to 4th meetings, it was found that the average level of adherence for the intervention group was 21.40 (P1), 23.80 (P2), 24.38 (P3) and 24.42 (P4).

Whereas for the group of patients without pharmacist counseling, the average level of adherence was lower, namely 21.31 (P1), 22.35 (P2), 23.56 (P3) and 23.58 (P4). After being tested statistically non-parametric (Kruskal-Wallis), there were significant differences between groups at each meeting (p-value = 0.00 <0.05). The data then continued with the Mann-Whitney test analysis, where the results obtained were significant differences between the levels of patient compliance at meeting 1 and meeting 2 (p-value = 0.00 <0.05) and meeting 2 and meeting 3 (p-value = 0.01 <0.05), which indicates that counseling intervention from the Pharmacist can improve patient compliance at the previous meeting. The same results were also obtained after further testing, the Binomial Test, whereas many as 38 patients in the intervention group had better adherence at the second meeting from the first meeting, 15 patients had better adherence at the third meeting from the second meeting and 10 patients had a better level of adherence at fourth meeting from the third meeting. This amount is more than the control group patients, which further strengthens the hypothesis, namely the presence of pharmacist counseling intervention can increase adherence to hypertension patients PROLANIS.

According to Putriani (2014) ^[23], compliance can occur due to the patient's desire to recover, but the role of the Pharmacist in explaining the drug is also important to increase the success of hypertension therapy. This study shows that the provision of drug counseling by pharmacists is very important to improve patient compliance in taking the drug so that the subsequent effects can increase the success of therapy in the treatment of hypertension.

MARS score less than 6 = low compliance; MARS score 6-24 = moderate compliance; MARS score 25 = high compliance.

  Source: ^[22]

Effects of Pharmacist Counseling on Systolic Blood Pressure (SBP)

Systolic blood pressure was also analyzed using the Kruskal-Wallis test, where the results obtained were asymp. Sig 0.00 <0.05, meaning that there were differences from each meeting. Mann Whitney test results obtained that the Asymp.Sig value. (2-tailed) is 0.012, the value is less than α = 0.050, so it can be concluded that after being given counseling intervention at the first meeting, there is a significant decrease in the patient's Systolic Blood Pressure (SBP). The analysis continued with the Wilcoxon and Binomial Test, where the number of patients whose SNP dropped at the second meeting was greater in the intervention group than in the control group. The same thing happened at the third and fourth meetings, where the total number of patients with SBP fell more than the group of patients who were given Pharmacist counseling compared to the group of patients who did not get Pharmacist counseling. Average systolic blood pressure also differed between the treatment group and the control group, namely P1 = 164 mmHg, P2 = 154 mmHg, P3 = 150 mmHg and P4 = 145 mmHg (treatment group) and P1 = 169 mmHg, P2 = 163 mmHg, P3 = 158 mmHg and P4 = 157 mmHg (control group). So it can be concluded that the provision of antihypertensive drug counseling by pharmacists can reduce the systolic blood pressure of prolanis patients in Primary healthcare centers. Complete results related to the use of antihypertensive drugs, levels of adherence and SBP can be seen in table 3.

a = KruskalWalis Test

b = Mann Whitney Test

c = Wilcoxon dan Binomial Test