J Basic Clin Physiol Pharmacol 2015; 26(3): 295–300
Ajmal Mankadavath, Dilip Chandrasekhar*, Tina Thomas, Fathimath Zuhra, Shanoob Kaipanthodi and Jafer Chalil Parambil
A prospective drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital Abstract Background: Hypertension is a chronic illness associated with high morbidity and mortality. Once hypertension is diagnosed, starting antihypertensive therapy on a longterm basis along with regular follow up is important. Standardizing treatment guidelines and conducting drug utilization studies at regular intervals help physicians to prescribe drugs rationally. The present study was conducted to analyze the prescription patterns of antihypertensive drugs in a tertiary care referral hospital in Malabar region, Kerala, India. Methods: The study was conducted at the General Medicine and Cardiology Department involving the in-patients. Patients suffering from essential hypertension with or without other co-morbidities were included in the study. The frequency and proportion of prescribing different groups of antihypertensive drugs as monotherapy or combination therapy, and prescription of fixed drug combinations (FDCs) were analyzed. A total of 200 hypertensive patients were included in the study. Patient data were collected from in-patient’s case sheets and direct interviews with the patients and their observers. Results: The majority of the patients were females with 56%, whereas the males comprised 44%, with most of the patients suffering from stage-II hypertension. The study revealed that a high proportion of the hypertensive patients had co-morbid diabetes mellitus. The most commonly prescribed class of antihypertensive drugs was angiotensin receptor blockers, followed by calcium channel blockers and β-blockers. With regard to patient *Corresponding author: Dilip Chandrasekhar, Associate Professor, Department of Pharmacy Practice, Alshifa College of Pharmacy, Perinthalmanna, Kerala, 679325, India, E-mail: [email protected] Ajmal Mankadavath, Dilip Chandrasekhar, Tina Thomas, Fathimath Zuhra and Shanoob Kaipanthodi: Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kizhattur, Perinthalmanna, Kerala, India Jafer Chalil Parambil: Department of General Medicine, Alshifa Hospital, Perinthalmanna, Kerala, India
therapy, 32.0% received monotherapy, whereas 68.0% received combination therapy, 16% of which received FDCs. Conclusions: The study shows that clinical pharmacists can play a key role in promoting rational prescription and improving adherence to medication. Keywords: antihypertensive; drug use evaluation; angiotensin receptor blockers; calcium channel blockers; JNC VII. DOI 10.1515/jbcpp-2013-0131 Received September 3, 2013; accepted July 17, 2014; previously published online August 19, 2014
Introduction Hypertension is one of the most common health problems both in the developed and developing countries. It is an important public health challenge because of its associated morbidity and mortality caused by cardiovascular diseases and the attendant cost of therapy. Worldwide, hypertension affects nearly 26% of the adult population. By 2025, it is estimated that 29% of the world population will have hypertension. In 2000, more than 972 million people had hypertension, and this figure is expected to increase to 1.56 billion by 2025. In India, about 66 million people are suffering from hypertension, 25% of which are from urban areas while 10% are from rural areas [1]. Once hypertension is diagnosed, starting antihypertensive therapy on a long-term basis along with regular follow up is important. It is essential to conduct drug use evaluation for monitoring, evaluation, and necessary modification in prescription practices to achieve rational and cost-effective therapy. Deaths resulting from hypertension and its associated health problems account for a third of global mortality. Scientific evidence suggests that such adverse outcome can be prevented by lowering
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296 Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital blood pressure effectively. A number of drugs in various combinations are commonly used for effective and longterm management of hypertension. Therefore, drug use evaluation studies that evaluate and analyze the medical, social, and economic outcomes of drug therapy, as well as observe the prescribing attitude of the physicians, are more meaningful [2]. The choice of drug to prescribe for hypertension changes at very short intervals. The efficacy, side effects – both short-term and long-term effects – and costs of the prescription drug are some of the factors responsible for changes in therapy. Accordingly, there is a need to conduct drug use evaluation studies to determine if the current usage is rational, effective and tolerated, and in accordance with current guidelines for treatment of hypertension [3]. Drug utilization studies can be used for improving medical care and cost containment, and are useful for measuring or comparing the economic impact of drug use in the population. By identifying adherence to guidelines in the current use of medicines, it is possible to reduce drug expenditure and improve the allocation of limited resources when the prescribed drugs are not usually the most cost-effective [3]. Increasing prevalence and incidence of hypertension and irrational prescription habits of physicians reflect the need for conducting drug utilization studies. The present study was conducted to analyze the prescription pattern of antihypertensive drugs and to reveal the new trends in hypertension treatment modality.
also included in the data collection form. Medication history of the patient was obtained from the patient medication slips, prescriptions, and from in-depth patient interview regarding medication use. The data were analyzed using SPSS 17.0 Windows Version (IBM Corporation, Armonk, New York, USA). The categorical variables, frequencies, and percentages (%) were computed with the χ2-test.
Results During the study period, a total of 200 hypertensive patients fulfilled the criteria for inclusion in the study. Demographic characteristics of the patients are depicted in Figures 1 and 2. Of the 200 hypertensive patients, 44% (n = 88) were males and 56% (n = 112) were females, indicating that hypertension is slightly more prevalent among females. The age difference between the two gender groups (p ≤ 0.1) was not statistically significant. The age of the subjects ranged from 25 to 100 years. Most of the hypertensive patients (49.3%) were in the age
Male 44% Female 56%
Figure 1 Demographic characteristics of the patients according to percentage. p = 0.270, i.e., no significant difference in the distribution of males and females in the study.
Materials and methods The study was conducted in one of the largest tertiary care teaching hospital in south Malabar region, Kerala, India for a period of 9 months. The hospital is unique and people from all over the world come to this hospital to avail of its services and receive treatment for various medical conditions. Ethical approval of the study was obtained from the Ethics Committee of Al Shifa Hospital PVT Ltd (ASH: ADM: 4038:012). The study was conducted at the General Medicine and Cardiology Department involving in-patients. Patients suffering from essential hypertension with or without other co-morbidities were included in the study. Depending on their age, the patients were divided into four groups ( 75 years). Hypertension was defined and staged according to the guidelines of the Seventh Report of the Joint National Committee (JNC VII) on the prevention, detection, evaluation, and treatment of high blood pressure [4]. Patient data were collected from in-patient’s case sheets and by conducting direct interviews with patients, their observers, and consulting physicians. Relevant data were extracted and recorded from eligible prescriptions using a data collection form. Documentation included demographic characteristics, pattern of drug use, and trends in treatment modality. Questionnaire for collecting patient’s view(s) about the disease were
Female
100%
Male
90% 80%
3.50%
6.50% 12%
70%
34%
60% 50% 40% 30%
5%
13.50% 10%
20%
15.50%
10% 0% Below 35 years 35–45 years
46–75 years Above 75 years
Figure 2 Demographic characteristics of the patients according to age. p = 0.181,.i.e., no significant difference in the distribution of males and females in each age group.
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Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital 297
25
22.5% 14.5%
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22% 13%
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Figure 4 Distribution of co-existing illness.
Among the three drug combinations, ARBs, β-blockers, and CCBs comprised the most commonly prescribed combination. About 16% (n = 32) of the patients were prescribed with fixed drug combinations (FDCs). Diuretics with ARBs, CCBs, or β-blocker (56.25%, n = 18) were the most frequently prescribed FDCs, followed by CCBs + β-blockers (31.25%, n = 10), and CCB + ARBs (9.37%, n = 3) (Figure 6).
50 45 40 35 30 47.5%
25 20
32%
15 10
13.5%
5
7%
0 One drug
Two drugs
Three drugs
Four drugs
Figure 5 Distribution of drug therapy regimen (antihypertensives).
•
56.3
. 32.8
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AR
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Stage 2 69.5%
2.5%
0
60 50 40 30 20 10 0
Stage 1 30.7%
12.5%
D
group of 46–75 years. Male patients below 45 years old outnumbered the female patients, indicating an earlier onset of hypertension among males in the study group. Most of the female hypertensive patients were above 45 years old. With regard to the patients’ family history, majority (61%, n = 122,) of the patients had a family history of hypertension, whereas 39% (n = 78) of them had none. With regard to food diet, the majority (84.5%, n = 169) of the subjects were non-vegetarians, most of which were regular consumers of various kinds of meat especially beef and food containing high amounts of saturated fat. Only a very small percentage (15.5%, n = 31) of them were vegetarians. With regard to social history, 8% (n = 16) of the subjects were alcoholic, 18.5% (n = 37) were smokers, and 4.5% were both alcoholic and smokers. Hypertension was classified according to the JNC VII criteria. Out of the 200 patients, 30.5% (n = 61) and 69.5% (n = 139) suffered from stage-I ( > 140/90 mmHg) and stage-II ( > 160/100 mmHg) hypertension, respectively (Figure 3). Of the reported hypertensive cases, 22.5% (n = 45) patients had associated diabetes mellitus (DM), 13% (n = 26) had dyslipidemia, 12.5% (n = 25) had coronary artery disease (CAD), 10% (n = 20) had asthma or chronic obstructive pulmonary diseases, 3% (n = 6) had DM with dyslipidemia, 2.5% (n = 5) had DM with CAD, 14.5% (n = 29) had no co-existing illness, and 22% (n = 44)had co-existing illness other than those mentioned above (Figure 4). With regard to treatment modality, 32.0% (n = 64) were on monotherapy, with the rest receiving combination therapy: 47.5% (n = 95) were prescribed with two drugs, 13.5% (n = 27) were prescribed with three drugs, and 7% (n = 14) were prescribed with four drugs (Figure 5). About 68% (n = 136) received some combination of antihypertensive agents. The most common drug combination was a 2-drug therapy of CCBs + β-blockers (20%, n = 40), followed by ARBs + diuretics (n = 56, 13%).
Figure 3 Classification of hypertension according to the JNC VII classification.
Figure 6 Distribution of combination therapy regimen.
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298 Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital The most frequently prescribed antihypertensive drug class in the study were ARBs (45.5%, n = 91), followed by CCBs (44.5%, n = 89), β-blockers (28%, n = 56), diuretics (24%, n = 48), and α-blockers (10.5%, n = 21) (Table 1, Figure 7). Table 2 shows the percentage of individual usage of antihypertensive drugs among study population.
Discussion Hypertension is a worldwide problem. Antihypertensive drugs are prescribed to control and prevent the morbidity and mortality associated with hypertension. Optimal blood pressure control is achieved by adherence to treatment guidelines and to the therapy. Adherence to treatment guidelines can be monitored by several methods. Drug utilization studies are one such important method. The study was conducted in a tertiary care referral hospital in Malabar region, Kerala, India. A total of 200 cases
Vasodilator Catecholamine depletor Central sympatholytics
were recorded and analyzed during a period of 9 months. The majority of the patients were females (56%). This finding may be due to the fact that 99% of the females in this study were housewives without any proper exercise and diet regimen and thus the prevalence among them of obesity, a risk factor for developing hypertension. This result is consistent with that of the study carried out by Susan et al. [5] and Khurshid et al. [6], but differs from that observed by Narendranth et al. [3] and Augustine et al. [7]. The majority of the patients were in the age group of 46–75 years. Greater prevalence of hypertension in this group may be due to changes in lifestyle, co-existing illness, hypertensive complications, or poor adherence to the therapy. This result is consistent with that obtained by Narendranth et al. [3] and Khurshid et al. [6]. The majority of the patients had a family history of hypertension (61.8%). This finding may be due to the fact that genetic factors may play a major role in the development of hypertension [6]. Also, the majority of the participants were non-vegetarians. Food containing high amounts of saturated and total fat is a major risk factor for hypertensive patients [7]. Among the subjects, 5% were alcohol drinkers although they were aware that they had hypertension,
Alpha+β blocker Centrally acting
Table 2 Distribution of number of drugs used.
ACE I
Drug
Alpha blocker Diuretic β-blockers CCB’s ARB’s 0
10
20
30
40
50
Figure 7 Percentage of antihypertensive drugs prescribed on the basis of pharmacological class. Table 1 Antihypertensive drugs prescribed on the basis of pharmacological class. Drug class
Number
Percent
ARBs CCBs β-Blockers Diuretic α-Blocker ACE I Centrally acting α + β-Blocker Central sympatholytics Catecholamine depletor Vasodilator
68 67 42 36 16 14 13 11 7 4 2
45.33% 44.67% 28.00% 24.00% 10.67% 9.33% 8.67% 7.33% 4.67% 2.67% 1.33%
Number
Percent
Losartan Metoprolol Nifidipine Amlodipine Carvedilol Furosemide Hydrochlorothiazide Moxonidine Prazosin Telmisartan Diltiazem Ramipril Enalapril Atenolol Clonidine Verapamil Olmisartan Reserpine Nebivolol Hydralazine Torsemide Bisoprolol Labetalol Methyldopa Propranalol Spironolactone
49 35 31 17 15 14 13 13 13 12 11 10 8 6 6 5 4 4 3 2 1 1 3 1 1 2
32.67% 23.33% 20.67% 11.33% 10.00% 9.33% 8.67% 8.67% 8.67% 8.00% 7.33% 6.67% 5.33% 4.00% 4.00% 3.33% 2.67% 2.67% 2.00% 1.33% 0.67% 0.67% 2.00% 0.67% 0.67% 1.33%
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Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital 299
whereas 3% used to drink alcohol but had reduced their alcohol intake and frequency after the diagnosis. Reduction in alcohol use is one of the major lifestyle modifications that have a positive effect on reducing blood pressure [7], although 92% of the patients were non-alcohol users. Smoking is the one of the major risk factors for developing hypertension. In this study, 122 patients were nonsmokers. This group consisted mostly of housewives, and about 18.7% of them were smokers. International guidelines suggest that cessation of smoking is one of the major steps in improving the lifestyle for reducing blood pressure [7]. Hypertension was staged according to the guidelines of the JNC VII. Among the patients, 30.7% suffered from stage-I ( > 140/90 mm Hg) and 69.3% from stage-II ( > 160/100 mm Hg) hypertension. The majority of the patients were suffering from stage-II hypertension, consistent with the findings of Joshi et al. [2] and Augustine et al. [7]. This study found that a high proportion of the hypertensive patients had co-morbid DM. This result is not surprising because it reflects the global trend. DM is followed by dyslipidemia, CAD, and asthma. Some patients had DM in combination with dyslipidemia or CAD. This result is consistent with that obtained by Augustine et al. [7]. The majority of the patients received combination therapy (68%). Given that most of the patients were suffering from stage-II hypertension, the JNC VII guidelines require combination therapy to treat the illness. Two drug therapies were prescribed most often, followed by three drug combinations, and four drug combinations. The prescription of more than three drugs for 7.3% patient may be attributed to the possibility of some patient presenting with multiple disease conditions. This observation is similar to that of Bajaj et al. [8]. The most commonly prescribed antihypertensive drug class was ARBs, followed by CCBs, β-blockers, diuretics, α-blockers, and angiotensin converting enzyme inhibitor (ACEI). ARBs are the most frequently prescribed group in hypertensive diabetics because angiotensin antagonism is reported to decrease the onset and progress of microvascular complications of hypertension and DM [7]. FDCs were commonly used (16%). This practice may be an attempt to improve patient compliance and reduce treatment costs. Such trend of multiple drug therapy in hypertension was also reported by Bajaj et al. [8].
Conclusions Hypertension is a progressive and complex disorder that is difficult to treat effectively in the long term. The present
study was conducted to analyse the prescription patterns antihypertensive drugs. Among the subjects, the females were found to be more prone to hypertension than males, with most of the patients belonging to the age group of 46–75 years. Diabetes was the major co-existing illness observed among the hypertensive patients. Prescription patterns of antihypertensive drugs changed with new drug introductions. ARBs and CCBs are the most commonly prescribed antihypertensive drugs. There is also a significant increase in the prescriptions of newer antihypertensive drugs, such as moxonidine. In this study, it was found that pharmacological management was given more importance than non-pharmacological management. In conclusion, this study strongly highlights the need for conducting studies on drug use evaluation to identify adherence to treatment guidelines in the current use of medicines and to reduce expenditure on medications. Clinical pharmacists can play a key role in promoting rational prescription and improving adherence to medication. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References 1. Biradar SS, Rajashekhar K, Srinivas R, Raju SA. Assessment of pharmacist mediated patient counseling on hypertension incompliance with quality of life in south Indian city. Int Res J Pharm 2012;3:18–26. 2. Joshi M, Rao BS, Khan GM. Study of drug use in essential hypertension and their compliance. Kathman U J Sci Eng Tech 2006;2:1–18. 3. Narendranath S, Somashekar HS, Reshma SR, Keerthi Sagar J, Ramachandra K. Prescriptive pattern of antihypertensives in tertiary care hospital using DU-90%. Int J Pharm Res Dev 2011;4:107–13. 4. Dipiro JT, Talbert RL, Matzke GR, Wells BG, editors. Pharmacotherapy: A pathophysiological approach. Washington, DC: The McGrawHill Companies, 7th ed. 130–71. 5. Susan R, Anu K, Achu T, Soumya G, Vijayakumar K, Anish TS. Antihypertensive drug compliance across clinic and
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300 Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital community settings, in Thiruvananthapuram, south India. Health Sci 2012;1:2. 6. Khurshid F, Aqil M, Alam MS, Kapur P, Pillai KK. Antihypertensive medication prescribing patterns in a university teaching hospital in south Delhi. Int J Pharm Sci Res 2012;3:2057–63. 7. Augustine L, Prasanth NV, Sanal Dev KT, Jasmin S, Kappekkat Y, Shinu C, et al. A study conducted on prescribing pattern
and cost of antihypertensive drugs in a tertiary level hospital in South Malabar region of Kerala. Der Pharma Chemica 2010;2:332–41. 8. Bajaj j K, Sood M, Singh SJ, Jerath P. Prescription patterns of antihypertensive drugs and adherence to JNC VII guidelines in a tertiary care hospital in north India. Int J Med Clin Res 2012;3:118–20.
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Ajmal Mankadavath, Dilip Chandrasekhar*, Tina Thomas, Fathimath Zuhra, Shanoob Kaipanthodi and Jafer Chalil Parambil
A prospective drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital Abstract Background: Hypertension is a chronic illness associated with high morbidity and mortality. Once hypertension is diagnosed, starting antihypertensive therapy on a longterm basis along with regular follow up is important. Standardizing treatment guidelines and conducting drug utilization studies at regular intervals help physicians to prescribe drugs rationally. The present study was conducted to analyze the prescription patterns of antihypertensive drugs in a tertiary care referral hospital in Malabar region, Kerala, India. Methods: The study was conducted at the General Medicine and Cardiology Department involving the in-patients. Patients suffering from essential hypertension with or without other co-morbidities were included in the study. The frequency and proportion of prescribing different groups of antihypertensive drugs as monotherapy or combination therapy, and prescription of fixed drug combinations (FDCs) were analyzed. A total of 200 hypertensive patients were included in the study. Patient data were collected from in-patient’s case sheets and direct interviews with the patients and their observers. Results: The majority of the patients were females with 56%, whereas the males comprised 44%, with most of the patients suffering from stage-II hypertension. The study revealed that a high proportion of the hypertensive patients had co-morbid diabetes mellitus. The most commonly prescribed class of antihypertensive drugs was angiotensin receptor blockers, followed by calcium channel blockers and β-blockers. With regard to patient *Corresponding author: Dilip Chandrasekhar, Associate Professor, Department of Pharmacy Practice, Alshifa College of Pharmacy, Perinthalmanna, Kerala, 679325, India, E-mail: [email protected] Ajmal Mankadavath, Dilip Chandrasekhar, Tina Thomas, Fathimath Zuhra and Shanoob Kaipanthodi: Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kizhattur, Perinthalmanna, Kerala, India Jafer Chalil Parambil: Department of General Medicine, Alshifa Hospital, Perinthalmanna, Kerala, India
therapy, 32.0% received monotherapy, whereas 68.0% received combination therapy, 16% of which received FDCs. Conclusions: The study shows that clinical pharmacists can play a key role in promoting rational prescription and improving adherence to medication. Keywords: antihypertensive; drug use evaluation; angiotensin receptor blockers; calcium channel blockers; JNC VII. DOI 10.1515/jbcpp-2013-0131 Received September 3, 2013; accepted July 17, 2014; previously published online August 19, 2014
Introduction Hypertension is one of the most common health problems both in the developed and developing countries. It is an important public health challenge because of its associated morbidity and mortality caused by cardiovascular diseases and the attendant cost of therapy. Worldwide, hypertension affects nearly 26% of the adult population. By 2025, it is estimated that 29% of the world population will have hypertension. In 2000, more than 972 million people had hypertension, and this figure is expected to increase to 1.56 billion by 2025. In India, about 66 million people are suffering from hypertension, 25% of which are from urban areas while 10% are from rural areas [1]. Once hypertension is diagnosed, starting antihypertensive therapy on a long-term basis along with regular follow up is important. It is essential to conduct drug use evaluation for monitoring, evaluation, and necessary modification in prescription practices to achieve rational and cost-effective therapy. Deaths resulting from hypertension and its associated health problems account for a third of global mortality. Scientific evidence suggests that such adverse outcome can be prevented by lowering
Brought to you by | McMaster University Authenticated Download Date | 10/25/15 4:22 AM
296 Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital blood pressure effectively. A number of drugs in various combinations are commonly used for effective and longterm management of hypertension. Therefore, drug use evaluation studies that evaluate and analyze the medical, social, and economic outcomes of drug therapy, as well as observe the prescribing attitude of the physicians, are more meaningful [2]. The choice of drug to prescribe for hypertension changes at very short intervals. The efficacy, side effects – both short-term and long-term effects – and costs of the prescription drug are some of the factors responsible for changes in therapy. Accordingly, there is a need to conduct drug use evaluation studies to determine if the current usage is rational, effective and tolerated, and in accordance with current guidelines for treatment of hypertension [3]. Drug utilization studies can be used for improving medical care and cost containment, and are useful for measuring or comparing the economic impact of drug use in the population. By identifying adherence to guidelines in the current use of medicines, it is possible to reduce drug expenditure and improve the allocation of limited resources when the prescribed drugs are not usually the most cost-effective [3]. Increasing prevalence and incidence of hypertension and irrational prescription habits of physicians reflect the need for conducting drug utilization studies. The present study was conducted to analyze the prescription pattern of antihypertensive drugs and to reveal the new trends in hypertension treatment modality.
also included in the data collection form. Medication history of the patient was obtained from the patient medication slips, prescriptions, and from in-depth patient interview regarding medication use. The data were analyzed using SPSS 17.0 Windows Version (IBM Corporation, Armonk, New York, USA). The categorical variables, frequencies, and percentages (%) were computed with the χ2-test.
Results During the study period, a total of 200 hypertensive patients fulfilled the criteria for inclusion in the study. Demographic characteristics of the patients are depicted in Figures 1 and 2. Of the 200 hypertensive patients, 44% (n = 88) were males and 56% (n = 112) were females, indicating that hypertension is slightly more prevalent among females. The age difference between the two gender groups (p ≤ 0.1) was not statistically significant. The age of the subjects ranged from 25 to 100 years. Most of the hypertensive patients (49.3%) were in the age
Male 44% Female 56%
Figure 1 Demographic characteristics of the patients according to percentage. p = 0.270, i.e., no significant difference in the distribution of males and females in the study.
Materials and methods The study was conducted in one of the largest tertiary care teaching hospital in south Malabar region, Kerala, India for a period of 9 months. The hospital is unique and people from all over the world come to this hospital to avail of its services and receive treatment for various medical conditions. Ethical approval of the study was obtained from the Ethics Committee of Al Shifa Hospital PVT Ltd (ASH: ADM: 4038:012). The study was conducted at the General Medicine and Cardiology Department involving in-patients. Patients suffering from essential hypertension with or without other co-morbidities were included in the study. Depending on their age, the patients were divided into four groups ( 75 years). Hypertension was defined and staged according to the guidelines of the Seventh Report of the Joint National Committee (JNC VII) on the prevention, detection, evaluation, and treatment of high blood pressure [4]. Patient data were collected from in-patient’s case sheets and by conducting direct interviews with patients, their observers, and consulting physicians. Relevant data were extracted and recorded from eligible prescriptions using a data collection form. Documentation included demographic characteristics, pattern of drug use, and trends in treatment modality. Questionnaire for collecting patient’s view(s) about the disease were
Female
100%
Male
90% 80%
3.50%
6.50% 12%
70%
34%
60% 50% 40% 30%
5%
13.50% 10%
20%
15.50%
10% 0% Below 35 years 35–45 years
46–75 years Above 75 years
Figure 2 Demographic characteristics of the patients according to age. p = 0.181,.i.e., no significant difference in the distribution of males and females in each age group.
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Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital 297
25
22.5% 14.5%
20
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Figure 4 Distribution of co-existing illness.
Among the three drug combinations, ARBs, β-blockers, and CCBs comprised the most commonly prescribed combination. About 16% (n = 32) of the patients were prescribed with fixed drug combinations (FDCs). Diuretics with ARBs, CCBs, or β-blocker (56.25%, n = 18) were the most frequently prescribed FDCs, followed by CCBs + β-blockers (31.25%, n = 10), and CCB + ARBs (9.37%, n = 3) (Figure 6).
50 45 40 35 30 47.5%
25 20
32%
15 10
13.5%
5
7%
0 One drug
Two drugs
Three drugs
Four drugs
Figure 5 Distribution of drug therapy regimen (antihypertensives).
•
56.3
. 32.8
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AR
B+
C
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Stage 2 69.5%
2.5%
0
60 50 40 30 20 10 0
Stage 1 30.7%
12.5%
D
group of 46–75 years. Male patients below 45 years old outnumbered the female patients, indicating an earlier onset of hypertension among males in the study group. Most of the female hypertensive patients were above 45 years old. With regard to the patients’ family history, majority (61%, n = 122,) of the patients had a family history of hypertension, whereas 39% (n = 78) of them had none. With regard to food diet, the majority (84.5%, n = 169) of the subjects were non-vegetarians, most of which were regular consumers of various kinds of meat especially beef and food containing high amounts of saturated fat. Only a very small percentage (15.5%, n = 31) of them were vegetarians. With regard to social history, 8% (n = 16) of the subjects were alcoholic, 18.5% (n = 37) were smokers, and 4.5% were both alcoholic and smokers. Hypertension was classified according to the JNC VII criteria. Out of the 200 patients, 30.5% (n = 61) and 69.5% (n = 139) suffered from stage-I ( > 140/90 mmHg) and stage-II ( > 160/100 mmHg) hypertension, respectively (Figure 3). Of the reported hypertensive cases, 22.5% (n = 45) patients had associated diabetes mellitus (DM), 13% (n = 26) had dyslipidemia, 12.5% (n = 25) had coronary artery disease (CAD), 10% (n = 20) had asthma or chronic obstructive pulmonary diseases, 3% (n = 6) had DM with dyslipidemia, 2.5% (n = 5) had DM with CAD, 14.5% (n = 29) had no co-existing illness, and 22% (n = 44)had co-existing illness other than those mentioned above (Figure 4). With regard to treatment modality, 32.0% (n = 64) were on monotherapy, with the rest receiving combination therapy: 47.5% (n = 95) were prescribed with two drugs, 13.5% (n = 27) were prescribed with three drugs, and 7% (n = 14) were prescribed with four drugs (Figure 5). About 68% (n = 136) received some combination of antihypertensive agents. The most common drug combination was a 2-drug therapy of CCBs + β-blockers (20%, n = 40), followed by ARBs + diuretics (n = 56, 13%).
Figure 3 Classification of hypertension according to the JNC VII classification.
Figure 6 Distribution of combination therapy regimen.
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298 Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital The most frequently prescribed antihypertensive drug class in the study were ARBs (45.5%, n = 91), followed by CCBs (44.5%, n = 89), β-blockers (28%, n = 56), diuretics (24%, n = 48), and α-blockers (10.5%, n = 21) (Table 1, Figure 7). Table 2 shows the percentage of individual usage of antihypertensive drugs among study population.
Discussion Hypertension is a worldwide problem. Antihypertensive drugs are prescribed to control and prevent the morbidity and mortality associated with hypertension. Optimal blood pressure control is achieved by adherence to treatment guidelines and to the therapy. Adherence to treatment guidelines can be monitored by several methods. Drug utilization studies are one such important method. The study was conducted in a tertiary care referral hospital in Malabar region, Kerala, India. A total of 200 cases
Vasodilator Catecholamine depletor Central sympatholytics
were recorded and analyzed during a period of 9 months. The majority of the patients were females (56%). This finding may be due to the fact that 99% of the females in this study were housewives without any proper exercise and diet regimen and thus the prevalence among them of obesity, a risk factor for developing hypertension. This result is consistent with that of the study carried out by Susan et al. [5] and Khurshid et al. [6], but differs from that observed by Narendranth et al. [3] and Augustine et al. [7]. The majority of the patients were in the age group of 46–75 years. Greater prevalence of hypertension in this group may be due to changes in lifestyle, co-existing illness, hypertensive complications, or poor adherence to the therapy. This result is consistent with that obtained by Narendranth et al. [3] and Khurshid et al. [6]. The majority of the patients had a family history of hypertension (61.8%). This finding may be due to the fact that genetic factors may play a major role in the development of hypertension [6]. Also, the majority of the participants were non-vegetarians. Food containing high amounts of saturated and total fat is a major risk factor for hypertensive patients [7]. Among the subjects, 5% were alcohol drinkers although they were aware that they had hypertension,
Alpha+β blocker Centrally acting
Table 2 Distribution of number of drugs used.
ACE I
Drug
Alpha blocker Diuretic β-blockers CCB’s ARB’s 0
10
20
30
40
50
Figure 7 Percentage of antihypertensive drugs prescribed on the basis of pharmacological class. Table 1 Antihypertensive drugs prescribed on the basis of pharmacological class. Drug class
Number
Percent
ARBs CCBs β-Blockers Diuretic α-Blocker ACE I Centrally acting α + β-Blocker Central sympatholytics Catecholamine depletor Vasodilator
68 67 42 36 16 14 13 11 7 4 2
45.33% 44.67% 28.00% 24.00% 10.67% 9.33% 8.67% 7.33% 4.67% 2.67% 1.33%
Number
Percent
Losartan Metoprolol Nifidipine Amlodipine Carvedilol Furosemide Hydrochlorothiazide Moxonidine Prazosin Telmisartan Diltiazem Ramipril Enalapril Atenolol Clonidine Verapamil Olmisartan Reserpine Nebivolol Hydralazine Torsemide Bisoprolol Labetalol Methyldopa Propranalol Spironolactone
49 35 31 17 15 14 13 13 13 12 11 10 8 6 6 5 4 4 3 2 1 1 3 1 1 2
32.67% 23.33% 20.67% 11.33% 10.00% 9.33% 8.67% 8.67% 8.67% 8.00% 7.33% 6.67% 5.33% 4.00% 4.00% 3.33% 2.67% 2.67% 2.00% 1.33% 0.67% 0.67% 2.00% 0.67% 0.67% 1.33%
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Mankadavath et al.: Drug use evaluation of antihypertensive drugs in in-patients of a tertiary referral care hospital 299
whereas 3% used to drink alcohol but had reduced their alcohol intake and frequency after the diagnosis. Reduction in alcohol use is one of the major lifestyle modifications that have a positive effect on reducing blood pressure [7], although 92% of the patients were non-alcohol users. Smoking is the one of the major risk factors for developing hypertension. In this study, 122 patients were nonsmokers. This group consisted mostly of housewives, and about 18.7% of them were smokers. International guidelines suggest that cessation of smoking is one of the major steps in improving the lifestyle for reducing blood pressure [7]. Hypertension was staged according to the guidelines of the JNC VII. Among the patients, 30.7% suffered from stage-I ( > 140/90 mm Hg) and 69.3% from stage-II ( > 160/100 mm Hg) hypertension. The majority of the patients were suffering from stage-II hypertension, consistent with the findings of Joshi et al. [2] and Augustine et al. [7]. This study found that a high proportion of the hypertensive patients had co-morbid DM. This result is not surprising because it reflects the global trend. DM is followed by dyslipidemia, CAD, and asthma. Some patients had DM in combination with dyslipidemia or CAD. This result is consistent with that obtained by Augustine et al. [7]. The majority of the patients received combination therapy (68%). Given that most of the patients were suffering from stage-II hypertension, the JNC VII guidelines require combination therapy to treat the illness. Two drug therapies were prescribed most often, followed by three drug combinations, and four drug combinations. The prescription of more than three drugs for 7.3% patient may be attributed to the possibility of some patient presenting with multiple disease conditions. This observation is similar to that of Bajaj et al. [8]. The most commonly prescribed antihypertensive drug class was ARBs, followed by CCBs, β-blockers, diuretics, α-blockers, and angiotensin converting enzyme inhibitor (ACEI). ARBs are the most frequently prescribed group in hypertensive diabetics because angiotensin antagonism is reported to decrease the onset and progress of microvascular complications of hypertension and DM [7]. FDCs were commonly used (16%). This practice may be an attempt to improve patient compliance and reduce treatment costs. Such trend of multiple drug therapy in hypertension was also reported by Bajaj et al. [8].
Conclusions Hypertension is a progressive and complex disorder that is difficult to treat effectively in the long term. The present
study was conducted to analyse the prescription patterns antihypertensive drugs. Among the subjects, the females were found to be more prone to hypertension than males, with most of the patients belonging to the age group of 46–75 years. Diabetes was the major co-existing illness observed among the hypertensive patients. Prescription patterns of antihypertensive drugs changed with new drug introductions. ARBs and CCBs are the most commonly prescribed antihypertensive drugs. There is also a significant increase in the prescriptions of newer antihypertensive drugs, such as moxonidine. In this study, it was found that pharmacological management was given more importance than non-pharmacological management. In conclusion, this study strongly highlights the need for conducting studies on drug use evaluation to identify adherence to treatment guidelines in the current use of medicines and to reduce expenditure on medications. Clinical pharmacists can play a key role in promoting rational prescription and improving adherence to medication. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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