Introduction

Hypertension is one the major leading causes of mortality and morbidity of cardiology patients as it is one of the major leading cause of cardiovascular events and requires a life long treatment (Kamath & Satish, 2016; Mateti, Mohd, Parmar, Konuru, & Kunduru, 2012). As it’s a lifetime therapy and used among majority population (Gupta & Gupta, 2009). Frequent assessment of prescription pattern and life style modifications is required as it lays a way for preparation and implementation of guidelines for effective patient care (Khurshid, Aqil, Alam, Kapur, & Kki, 2012; Kotchen, 2010). In India its prevalence is about 17-21% (Kamath et al., 2016). It has been also observed that prevalence rate has been varying with age 56.3% in patients of age > 60 yrs, 64.2% in > 70yrs and community. Urban community shows more prevalence than rural one (Anchala et al., 2014). Obese and overweight patients had a prevalence rate of 31% (Jangir et al., 2019). It is observed that 1.5 million deaths has been occurring annually by cardiovascular events. Hypertension itself doesn’t lead to serious cardiovascular condition or mortality but it lays a way for occurrence of serious events through its complications as it effects on all parts of the body. The raised blood pressure effects various organs and blood vessels and lead to a serious event (Erickson, Slaughter, & Halapy, 1997). Hence it should be lowered by using a drug among the numerous class of antihypertensives. Here pharmacists also plays a vital role to achieve treatment outcome and to improve quality of life. They act as a bridge or rope between health care professionals and helps to achieve individual treatment goals by personalized treatment regimen and to conduct studies (Suthar, Patel, & Shelat, 2019). As it’s a well known fact that the symptoms of hypertension will not get recognised by the patient in initial stages until it develops some serious effect or some temporary illness like fatigue,vertigo, severe and repeated headaches (Arief, Harika, & Satyanarayana, 2013). It is stated that the quality of most of the prescriptions were unsatisfactory with the guidelines which is leading to poor compliance. It is also observed that simplifying the daily doses increases adherence towards prescription or regimen prescribed (Konwar, Paul, & Das, 2014). As the time changes new drugs, formulations and combinations are available. Hence drug utilization studies, prescription pattern and prescriber attitudes towards prescription will help in modification/ amendment or preparation of new guidelines (Haq, Singh, Sehgal, Kumar, & Kaur, 2019; Jangir et al., 2019; Khurshid et al., 2012). Hence, our study is designed to asses the present trend of prescription and its compliance with guidelines.

In India prescriber usually prescribes by using brand names only. Now a days government is taking measures to provide prescription by including generic name. Hence pharmacoeconomic studies plays a vital role in rational use and drug compliance, as cost of drug is one of the factor for noncompliance due to increased economic burden (Dragomir et al., 2010; Kamath et al., 2016) . That’s why we have performed cost analysis to assess the economic burden on each patient.

Methodology

Aim and objectives

To study the prescription pattern of antihypertensive drugs prescribed and to perform the cost analysis to know economic burden on the patient.

Study Site

This study was carried out in out-patient and in-patient department of multispecialty hospital in Guntur.

Study design

This is a prospective observational and non interventional study. As it involves data collection from reports the patient file and doesn’t involve any biological sample taken from patient for the purpose of study.

Study Period

This study has been carried out for a period of 23 months. i.e.; from 2^nd April 2018 to 8^th March 2020.

Study Criteria

Inclusion Criteria

• Patients having cardiac issues and are using anti hypertensives.

• Patients above the age of 18 yrs.

• Patients of IP and OP of cardiology department who meets the criteria.

• Patients of both the gender.

• Patients who are willing to participate in the study and are willing to give written informed consent.

Exclusion Criteria

• Patients who are not willing to participate in the study.

• Patients who are willing to participate but refused to give informed consent.

• Paediatric patients.

• Patients suffering from renal failure and hepatic failure has not been included.

• Patients who were not using any antihypertensive.

• Pregnant women and lactating mothers were excluded.

Source of Data

All the relevant and necessary data had been collected from,

• Demographic data in the record has been collected and some of the necessary data not in the record has been collected by enquiring the patient or their care taker.

• Data relating to disease history, duration of treatment, number of pills per day, tests being conducted were collected from patient records.

• Treatment chart given to the patient.

• And other relevant sources depending upon patient record like bills of tests etc.

• Changes in the drug therapy has also been noted and documented for each visit and the tests carried out to monitor has been recorded.

Materials and Methods

A relevant data collection form has been designed which contains all the information required for the study. Which includes the demographic details of the patient, social habits, occupation, educational status and co morbid conditions the patient experiencing. It also contains information regarding the treatment chart and drugs prescribed and modifications in therapy. It also contains the information regarding the cost of the travelling , hospital cost and necessary data required for the cost analysis.

Softwares used

MS-excel 2007 has bee used for initial evaluation and analysis. Later SPSS 16 version has been used for statistical evaluation of results.

Sequence of study

All the patients were informed regarding the study and its objectives, the data required and confidentiality of their personal information along with the subject rights and responsibilities in layman language and written informed consent was taken. At first initial evaluation was performed for all patients and then patients who meets criteria were included in the study by entering data in the entry forms and later analyzed for results.

Results and Discussion

Among the numerous patients that visit to study sites we have approached as many patients as possible and counselled the patient regarding their condition and drug therapy, necessary precautions to be taken. Mean while we observed the patient data and if the patient meets the study criteria then they were included in the study. Atlast we got total number of subjects (N) = 1250. Among them some of subjects later excluded from study (194 excluded) because during follow up they did not visit the study site for checkup and some of them had changed the hospital to get treated by a new prescriber. Some of the patients has developed renal or hepatic failure and meets the exclusion criteria. Some of the patients who were initially intrested in the study(113 discontinued) but later they were not willing to continue. So we have dicontinued them from the study. Among the remaining subjects we were unable to followup 81 patients due to wrong phone numbers and some were not able to recognise us when we called them as remainder for visit to hospital. Finally the total number of subjects actually included in the study (n) = 1056.

Gender Distribution

The subjects who were finally participated in the study were 1056 and among them there were 621 males and 435 females. Indicating males were 18% more prone to cardiovascular events when compard to males. Shown in Table 1 and represented in Figure 1. Table 2 shows the mean age of subjects with their standard deviation.

Age Distribution

Most of the patients were belong to 61 to 70 years of age group later occupies 51-60 years of age. As we had seen that there is not much difference in between the percentage, we can conclude that 51-70 yrs of age as high incidence of cardiovascular events. Patients below (18-40 yrs) 40yrs of age are very few. Shown in Table 3 and represented in Figure 2.

The mean age of male patients = 60.44 + 8.13 yrs

The mean age of female patients = 59.73 + 10.55 yrs

Mean age of total population = 60.13 + 9.22 yrs

Hence there is no much differnce in the mean age group of males and females for experiencing cardiovascular events according to our results obtained.

Distribution of patients according to Comorbidities

Most of the patients were suffering from Coronary artery disease (CAD), they were about 34.85% occupying the highest incidence. 15.15% were suffering with hypertension (HTN), 13.64% with dialated cardiomyopathy (DCM), 28.79 % were suffering with both hypertension and diabetes mellitus (DM) and finally 7.57% were suffering with myocardial infraction (MI) occupying least cardiovascular event when compared to others. Shown in Table 4 and represented in Figure 3.

Educational / literacy level of the patients

Among the patients about half of them are illiterate i.e.; 50.38%. remaining 49.62% were considered as literate because 27.94% has qualified ssc or 10^th class, 8.42% has discontinued education after inter, 7.67% has successfully completed their degree and the last 5.59% of patients has education of post graduation and higher. Shown in Table 5 and represented in Figure 4.

Occupation

Most of the patients 35.05% were daily wages, we have included farmers also under daily wages. Next occupies 25.57% patients who were housewives (females) or patients with no jobs, no jobs in the since they were not doing any work due to their age or other related factors, they just lead life with their family as liabilities. 15.24% were having their own businesses related to various fields. 7% members were doing jobs either in private sector or government sector. 17.14% were retired employees among them some are pensioners and some of them are not pensioners. Shown in Table 6 and represented in Figure 5.

Social Habits

Social habits is one of the most risk factors of various diseases or disorders. 38.54% of the patients are tobacco consumers either in chewable form or through smoking. 31.53% of patients dose not have any habits like smoking, consumption of tobacco and alcohol. 9.09% are only alcoholics they doesn’t smoke or consume tobacco, among them mostly are daily consumers, rest consume on weekends and some occasions. 20.84% of population are both alcoholics and tobacco consumers. Shown in Table 7 and represented in Figure 6.

Prescription Pattern

Total number of patients (n)=1056.

For each visit the physician use to prescribe, either it maybe continue the same or slight change in the prescription. So, we considered as a new prescription for each visit. Hence, 1056 x 4 visits = 4224 total number of prescriptions.

Among the 4224 prescriptions, dual therapy has been highly prescribed (43.18%) as effectiveness and treatment outcome is better when compared to single drug therapy which has been provided in 35.79% prescriptions. Dual therapy is generally preferred in patients who were not able to lower their raised blood pressure to their therapeutic goals. 17.04% prescriptions were prescribed with triple therapy. 2.84% prescriptions with quadruple therapy and the least 1.13% prescriptions with penta therapy. These quadruple and penta therapy were prescribed for patients with severe illness. Shown in Table 8 and represented in Figure 7.

Monotherapy

Among 4224 prescriptions 1512 (35.79%) prescriptions were monotherapy. In the monotherapy beta blockers were highly preferred. In them metoprolol and atenolol were highly preferred. Next occupies Angiotensin Receptor Blockers (ARB’s) 13.76%. among them Telmisartan was highly used drug. Next occupies the Calcium channel blockers (CCB’s) which were 12.69% and highly used are nifidepine and clinidepine. 5.69% were diuretics and 3.17 % angiotensin converting enzyme inhibitors (ACEI). Last 2.78% prescriptions contain α+β blockers. Shown in Table 9 and represented in Figure 8.

Dual therapy

Among the 4224 prescriptions 1824 (43.18%) were having dual therapy. The combinations used here are mostly fixed dose combinations in a single pill. Among the combinations being used beta blockers with ARB are highly used it occupies about 19.73%. Though this combination is not an idle one but some studies has shown effectiveness. 17.27% were beta blockers with CCB and which is more effective in lowering the raised blood pressure when compared to monotherapy. 17.12% were ARB with diuretics and it has been a good and preferable combination. 15.78% were two diuretics combined with sub classes variation. 13.16% were ARB with CCB. 5.26% were Beta blocker with alpha blockers. 3.94% were combination of beta blocker with diuretics. 3.78% were ACE with diuretics. Rest 2.64% and 1.32% were combination of ARB with (α+β) blocker and CCB with α blocker respectively. Shown in Table 10 and represented in Figure 9.

Triple therapy

Among the 4224 prescriptions 17.04% (720) was triple therapy. The combinations used here are mostly fixed dose combinations in a single pill and rare combinations are of two pills. It is preferred in patients whose raised blood were combination of ARB with BB and CCB. 13.33 % occupies with three types of combination they pressure was not controlled by using dual therapy. According to our observations the mostly used combination is beta blocker (BB) with two diuretics which occupies 23.34% of prescriptions of triple therapy. 20% prescriptions are ARB with BB and diuretic (DI), ARB with CCB and DI, BB with CCB and DI. 6.67% prescription occupies with 2 types of combinations they are two CCB combined with ARB and a combination of ACE, CCB with DI. Last 3.33% were combination of ARB with two diuretics. Shown in Table 11 and represented in Figure 10.

Quadruple therapy

Among the 4224 prescriptions 2.84% (120) was quadruple therapy. Here combination of ARB,BB with two DI and two ARB with two BB are mostly used and occupies 40% each. The last 20% combinations contains two diuretics combined with ARB and CCB. Here the combinations used are fixed dose combination with 2 pills or non fixed dose combinations with multiple pills. In quadruple therapy no combination is of a single pill. Shown in Table 12 and represented in Figure 11.

Penta therapy

Combinations used in penta therapy are non fixed dose combinations with multiple pills. Among the total prescriptions it occupies 1.13% stating less used. It is generally preferred in critically ill patients. The drugs used under this combination are ARB,CCB, (α+β) blocker with two diuretics. Shown in Table 13.

Cost Analysis

The cost analysis was determined by considering the direct medical and indirect medical costs imposed on the patients included in the study.

Cost of antihypertensive medications, cost of alternative medicines prescribed (gastro protective drugs, statins, antiplatelets and other cardiac drugs), cost incurred for undergoing 2D echocardiography and other lab tests along with outpatient fees were included in the direct medical costs. Charges incurred on the patients for travelling from their residence to hospital and loss of pay due to their hospital visits were included in indirect medical costs.

In direct medical cost category we observed that an average of Rs.1582.72 was incurred on patients for antihypertensive medications, Rs.1943.63 for alternative medicines, Rs.1000 for undergoing 2D echocardiography, Rs.514.77 for other lab tests, and Rs.600 for outpatient fees for their four visits. From this, the total average of direct medical cost was found out to be Rs.5641.12.

In indirect medical cost category we observed that an average of Rs.263.63 was incurred on patient for travelling charges, and Rs.413.6 for loss of pay during their hospital visits. Fro By combining the total average of direct and indirect medical costs, we got the total average economic burden of Rs.6318.39 on patients for four visits (6 months) to hospital which shows that a burden of Rs.1579.60 was imposed per visit. Shown in Table 15; Table 14 .

Monotherapy

According to (Haq et al., 2019) BB (49.95%) was highly used as monotherapy. ARB (31.78%), CCB(9.15%), DI(4.56%), ACEI (4.56%). In our study we observed BB (61.91%) , ARB (13.76%), CCB (12.69%), DI (5.69%), ACEI (3.17%) and complies with (Haq et al., 2019) α +β blockers (2.78%). According to (Singla, Singh, Gupta, & Sehgal, 2018) ARB (45.47%), BB(9.09%), CCB(22.75%), ACEI(20.64%), DI (2.05%). According to (Romday, Gupta, & Bhambani, 2016) DI (29.48%) is highly used but it’s a contradict result to our observations. CCB (21.96%) which is next to highly used similar to our observations. ARB (16.18%), BB (10.4%), ACEI (19.07%), Alpha antagonists (2.91%). According to (Kuchake, Od, Surana, Patil, & Dighore, 2009; Malpani, Waggi, Panja, & Christien, 2018; Mishra, Kesarwani, & Keshari, 2017; Philip et al., 2016) and (Ashok et al., 2015) CCB (51.7%, 54%, 42.7%, 55% & 31.03% rspectively) was highly used as monotherapy. According to (Dhanaraj, Raval, Yadav, Bhansali, & Tiwari, 2012) ACE-Inhibitors (46.8%) was highly used. According to (Tandon et al., 2014) ARB (40.42%) was highly used.

Dual therapy

According to (Haq et al., 2019) ARB+BB (30.84%), ACEI+BB (25.48%) are the highly used combination. ACEI+DI(1.82%), ARB+CCB(10.92%), ARB+DI(12.74%), BB+CCB(12.74%), BB+DI (1.82%), CCB+DI (3.64%) has been used. In our study we observed BB+ ARB are highly used it occupies 19.73% and complies with (Haq et al., 2019) and (Singla et al., 2018) (47.46%) but (4.81%) according to (Romday et al., 2016) entirely contradict to our observation. BB+CCB (17.27%) and in (Singla et al., 2018) (4.13%) but (Romday et al., 2016) indicates 12.04% similar to our observations. (17.12%) ARB+DI but according to (Singla et al., 2018) (24.76%) indicating next highly used combination and 21.67% indicated in (Romday et al., 2016). 15.78% were two diuretics combined with sub classes variation. (13.16%) ARB + CCB and (13.24%) in (Romday et al., 2016) indicating similar result to our study but in (Singla et al., 2018) (4.13%) indicating less used. (5.26%) BB+ alpha blockers. (3.94%)BB+DI , 6.02% at (Romday et al., 2016) and in (Singla et al., 2018) (5.1%) similar to our observations. (3.78%) ACEI+DI and in (Singla et al., 2018) (6.19%) but highly used (26.48%) according to (Romday et al., 2016) entirely contradict to our observation. (2.64%) ARB + (α+β) blocker was observed in our study. (1.32%) CCB + α blocker similarly indicated in (Romday et al., 2016) (1.3%). According to (Singla et al., 2018) BB+ACEI (5.15%), CCB+DI (3.08%) were also used. According to (Romday et al., 2016) BB+ACEI (4.81%), CB+DI (9.63%) were also used as in (Singla et al., 2018).

Triple therapy

According to (Haq et al., 2019)triple therapy combinations used were ACEI+BB+CCB (3.33%), ARB+BB+CCB (36.63%) indicating next to highly used combination, ARB+BB+DI (46.62%) stating highly used combination, ARB+CCB+DI (9.99%) and BB+CCB+DI (3.43%). In our study we observed BB+DI+DI (23.34%) as highly used combination but (Singla et al., 2018) states least used combination(1.93%). ARB+BB+CCB(20%) which is next to highly used combination according to (Haq et al., 2019) and (Singla et al., 2018) (29.39%) occupies same place in our study. ARB+BB+DI (13.33%) which is highly used combination according to (Haq et al., 2019) and (Singla et al., 2018) (45.11%) and occupies third place in our study. CCB+ARB+DI (13.33%), BB+CCB+DI (13.33%). ARB + CCB +CCB & ACE+CCB+DI are 6.67%, ARB+DI+DI (3.33%). According to (Singla et al., 2018) ACE+BB+DI (17.72%). BB+CCB+DI (1.93%) and ARB+CCB+DI (3.92%) are less used which is similar to our observations. According to (Romday et al., 2016) ARB+CCB+DI (19.78%) was highly used indicating similarly with our study. ARB+BB+DI (8.47%), ARB+BB+CCB (16.11%) used indicating similarly with our study. ACE+CCB+DI (19.78%), ARB+DI+DI (11.3%) indicating contradict to our observations. ACEI+BB+DI (8.47%), ACE+BB+CCB (16.09%) which are not used in our study.

Quadruple therapy

According to (Haq et al., 2019) the quadruple combination used is ACEI+ARB+BB+DI only one type of combination is used and in our study we observed 3 types of combination ARB+BB+DI+DI (40%), ARB+ARB+BB+BB (40%) and ARB+CCB+DI+DI (20%). According to (Singla et al., 2018) ARB+BB+DI+DI (50.12%) combination is highly used which is nearly similar to our observations. ARB+BB+DI+CCB (33.38%), CCB+CCB+DI+ARB (5.5%). ARB+DI+DI+CCB(5.5%) combination is less used which is nearly similar to our observations but according to (Romday et al., 2016) it is highly used 60.04%. According to (Romday et al., 2016) CCB+BB+DI+DI (39.96%) is another combination used.

Penta therapy

According to (Singla et al., 2018) the penta therapy combination used is ARB+DI+DI+BB+CCB and in our study we observed ARB+CCB+ (+β) blocker+DI+DI. In both the studies ARB+DI+DI+CCB has commonly combined with another drug.

Cost Analysis

According to (Mudhaliar et al., 2017) the cost of anti hypertensive medication (average per patient) is Rs 3823.58 /- per year indicating Rs 1911.79 /- which is nearly similar to our study as it marginal higher than the cost of our study observations. According to (Rachana, Anuradha, & Shivamurthy, 2014) cost of anti hypertensive medication of monotherapy is Rs 2362.69 + 1521.67, polytherapy is Rs 2525.72 + 853.33, fixed dose combination is Rs 2576.48 + 1399.47 per year. Upon calculation for six months the average antihypetensives cost is Rs 1244.14 + 629.07 for all type of therapies which is mostly similar but little lower than our study observations.

Conclusions

Our study provides a prescription pattern of antihypertensives and cost analysis among cardiology patients which indicates the rational use of drugs to an extent, however there should be further research is required to reduce economic burden. During counseling we have observed that most of the coronary artery disease patients were aware that there is a type of block in blood vessels. Rest of the patients were not aware of their cardiovascular event they are suffering. They believe that they were suffering from increased blood pressure. We have also observed that most of them suffering from hypertension were having left ventricular hypertrophy and fewer are with arrhythmias. Most of the guidelines suggest usage of diuretics as first line therapy but in our study beta blockers has been preferred more as monotherapy. A regular monitoring of prescription pattern seems to be very much useful for good results of treatment outcome because it indicates the current status and usage of medications according to standard guidelines or not and lay a way to asses the reason for deviation. Further research is to be required for rational therapy based on economic status and conditions of the patient. Pharmacoeconomics plays a vital role in promotion of drug compliance and rational use of drug. Fewer studies are available in this area in India. Hence studies related to economic burden, cost effective, cost minimization etc economical studies should also be encouraged.

Acknowledgement

We are greatful for all the hospitals and subjects who have given dedicated support for our study. We would like to thank all the participants for participating in the study and giving their valuable time.

Abbreviations

ACE-I= Angiotensin Converting Enzyme Inhibitors; ARB = Angiotensin Receptor Blocker; BB = Beta blocker; CAD = Coronary artery disease; CCB = Calcium Channel Blocker; DCM = Dilated cardiomyopathy; DI = Diuretics; DM = Diabetes Mellitus; HTN = Hypertension; MI = Myocardial Infraction.

Funding Support

The authors declare that they have no funding support for this study.

Conflict of Interest

The authors declare that they have no conflict of interest for this study.