Drug Utilization Evaluation of Antihypertensives in A Superspeciality Hospital

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1 Research Article Drug Utilization Evaluation of Antihypertensives in A Superspeciality Hospital Mahalaxmi Mohan Department of Pharmacology, MGVs Pharmacy College, Department of Pharmacology, Nashik , India. ABSTRACT An open label, prospective and comparative study on effectiveness of antihypertensive agents in the inpatient and out-patient department of a super specialty hospital was studied. Patients of either sex aged between years suffering from mild to moderate hypertension were randomly selected. Various classes of antihypertensive drugs used for the management of hypertension were Calcium channel blockers (CCBs); Angiotensin converting enzyme inhibitors (ACEI); beta adrenergic blockers (BBs); Angiotensin receptor blocker (ARBs); and diuretics. The side effects and satisfaction levels in both monotherapy and combined therapy were noted. Out of 180 patients of stage 1hypertension: 25% patients were treated with ARB S, 35% patients were treated with CCB S, 20% patients with CCB S + diuretics, 10% with ACE inhibitors and 10% patients were treated with BBs + CCB S. Similarly, out of 250 patients of stage 2hypertension: 20% patients were treated with CCB S+ diuretics, 30% patients were treated with CCB S + ARB S, 25% patients with BBs + CCBs, 15% patients with BBs + ARBs + Diuretics and 10% patients were treated with ACEs + BBs + CCBs. Similarly, out of 25 patients of severe hypertension: 40% patients were treated with BBs + CCBs and 60% patients were treated with CCBs + ARBs. Two drug combined therapy was more effective as compared to three drug combined therapy and mono therapy. Amongst various mono therapy and combination therapy, Amlodipine showed excellent satisfaction level when used alone and in combination with other drugs. The DDD/100 bed day s value for Amlodipine was found to be Key words: Defined daily dose (DDD), drug utilization, hypertension, super specialty hospital Received 28 July 2016 Received in revised form 11 August 2016 Accepted 13 August 2016 *Address for correspondence: Mahalaxmi Mohan, MGV s Pharmacy College, Department of Pharmacology, Mumbai-Agra Road, Panchavati, Nashik , India. E mail: mm_nasik@yahoo.co.in INTRODUCTION Hypertension (HTN) is an important public health challenge in both developing and developed countries resulting in high rates of mortality and morbidity. Socio-economic, behavioral, nutritional and public health issues have led to increase in cardiovascular disease (CVD), including stroke and myocardial infarction throughout the world. [1] A surplus of new drugs is now available, leading to better quality of life for these patients. Number of drugs in various combinations is generally used for effective long-term management. [2-4] Drug utilization studies, which evaluate, analyze the medical, social and economic outcomes of the drug therapy, are more significant and observe the prescribing attitude of physicians with the aim to provide drugs rationally.[5]drug utilization study is an important tool to study the clinical use of drugs in population and its impact on health-care system. [6,7] The medical intensive care unit (MICU) is a setting where the multiple medications are prescribed to patients. Periodic evaluation of drug utilization in MICU is necessary for optimization of health care system, proper use of resources and making prescription policy. [8] The assumed average maintenance dose per day for a drug used for its main indication in adults is called defined daily dose (DDD). Use of DDD is an important tool to compare the drug utilization among different clinical setup within a country and between different countries. DDD/100 bed-days provide a rough estimate of drug consumption in hospital inpatient and it is a fixed unit of Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 1

2 measurement independent of formulation and price. [9,10] The Anatomical Therapeutic Chemical (ATC) is used for the classification of active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties. It is controlled by the World Health Organization Collaborating Center for Drug Statistic Methodology (WHOCC), and was first published in [11] This pharmaceutical coding system divides drugs into different groups according to the organ or system on which they act and their therapeutic and chemical characteristic. Each bottom level ATC code stands for pharmaceutically used substance, or a combination of substances, for a single indication (or use). This means that one drug can have more than one code: Amlodipine, for example, has C08CA01 as a drug for oral treatment. On the other hand, several different brands share the same code if they have the same active substance and indication. [11,12] In the present study, we have evaluated the drug utilization pattern among hypertensive and calculated the DDD for commonly used drugs in a superspeciality hospital (Apollo Hospital, Nasik). MATERIALS AND METHODS Type of study-it was an open label, prospective and comparative study. Place of study- The study was conducted in Apollo Hospital, Nashik, which is a leading hospital in the country, it is a 200 bedded hospital, offering 24 hours service to patients. Study population- All hypertensive patients of outpatient Department (OPD) and Inpatient Department (IPD) were diagnosed by hospital physician. Patients with systolic blood pressure above 140 mmhg and diastolic blood pressure above 90 mmhg were included in the study. Comorbid with hypertensive and diabetic patients were also included. Sample size-the sample size was 455. Study period- Study period was carried for six months from Aug 2015 to Jan Study criteria- Inclusion criteria-subjects who were newly diagnosed with established history of hypertension, subjects who were> 25 years and either gender, subjects with co-morbid diseases such as diabetes mellitus, hypertension, ulcer, acute pulmonary edema, myocardial infarction and coronary artery disease associated with all stages of hypertension, and subjects who are willing to participate and have submitted informed consent form were included in the study group. Exclusion criteria Subjects with significant hepatic and renal diseases, pregnant women, subjects who had psychiatric illness, who were chronically ill-looking, and subjects who were not treated with antihypertensive drug, were not included in the study. Data Collection Subjects were interviewed and selected with face to face interaction based on inclusive and exclusive criteria for the study. Standard subject s sociodemographic and clinical feature data collection forms were prepared and the particulars like age, gender, subject IP/OP number, diagnosis, subjects present/past medical history, number of days hospitalized, knowledge on hypertension, therapy duration for other major complication like coronary artery disease (CAD), myocardial infarction, hypertensive heart disease, diabetic complications and individual data were collected from individual subjects case sheets. In order to evaluate drug utilization pattern of antihypertensive medications in a superspeciality hospital, WHO core drug use indicators and WHO ATC/DDD metric system were used. The assessment of prescribing pattern for rationality of drug therapy in hypertensive study population based on WHO core drug use indicators included the prescribing indicators, patient care indicators, and facility indicators. The individual subject s case sheet data were gathered and enrolled manually in ordinary prescriber indicator form and then data was analyzed to find out the number of drugs prescribed, percentage of prescribed drugs analyzed from Nashik Standard Treatment Guidelines Apollo Hospital drug list. Statistical Analysis Measurement of drug utilization of antihypertensive medication was made using WHO ATC/ DDD metric system. [12,13] Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 2

3 Number of items used x Amount of drug per item (mg) Defined daily dose = WHO recommended DDD of drug Drug consumption in the study period x 100 DDD/ 100 bed-day = DDD X period of study X Bed Strength X Average Occupancy Total inpatient days for given period x100 Bed occupancy rate = Available beds x Number of days spent in study period RESULTS A total of 455 patients were consulted during the six month study period, in an outpatient and inpatient department of Apollo Hospital. Out of these 455 prescriptions, 180patients were in the age group of years, followed by 250 patients in years and 25 patients were 70 years, Male patients were found to be higher compared to female counterparts. Measurement of drug utilization of antihypertensive s medication using WHO ATC/ DDD metric system-measurement of drug utilization of antihypertensive medication were observed for the following drugs: Angiotensine converting enzyme inhibitors (ACE I)- Enalaprile and Ramipril; beta blocking agents- Metoprolol, Atenolol, Propranolol, Nebivolol; calcium channel blocker-amlodipine and Verapamil; Angiotensine II converting enzyme inhibitor- Telmisartan and Diuretics- Furosemide and Hydrochlorothiazide. A total of 455 subjects were randomly collected and enrolled in the study. The number of beds available in the ward was 200 and the number of days spent was 180 days. The average bed occupancy rate during this study period was Amlodipine medication was most frequently utilized and showed DDD/100 bed days followed by Ramipril, with DDD/100 bed days and Enalpril, with DDD/100 bed days. The impressed number of DDD assigned for each antihypertensive is given by the DDD/ATC WHO metric system. [14] Table 1: Antihypertensive drug consumption in general medicine wards using DDD/100 beds days Antihypertensive Drugs ATC Code WHO recommended DDD(mg) DDD/100 bed days Amlodipine C08CA Ramipril C09AA Enalpril C09AA Furosemide C03CA Nebivolol C07AB Telmisartan C09CA Atenolol C07AB Verapamil C08DA Hydrochlorothiazide C03AA Propranolol C07AA Metoprolol C07AB Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 3

4 Distribution of patients among stages of hypertension-out of 455 hypertensive patients, 180 patients (39.56%), 250 patients (54.94%), 25 patients (5.49%) were having stage 1, stage 2, and severe hypertension respectively (Table 2). Table 2: Distribution of patients among various stages of hypertension Stage of hypertension Number of hypertensive patients Stage Stage Severe Percentage (%) Gender wise distribution among stages of hypertension Out of 299 male hypertensive patients: 132 (44.14%) had stage 1 hypertension, 139 (46.48%) had stage 2 hypertension and 28 (9.36%) were with severe hypertension; whereas out of 156 female hypertensive patients, 85 patients (54.48%) were with stage 1 hypertension, 52 patients (33.33%) had stage 2 hypertension and 19 patients (12.17%) had severe hypertension (Table 3). Table 3: Gender wise distribution among various Stages of hypertension Male (n = 299) Female (n = 156) Stage 1 Stage 2 Severe Stage 1 Stage 2 Severe 132(44.14) 139(46.48) 28(9.36) 85(54.48) 52(33.33) 19(12.17) Medical history of the hypertensive patients-majority of patients (140) experienced tingling sensation as common symptom before diagnosing hypertension. Other symptoms observed were chest pain, headache, dizziness and blurred vision (Figure 1). Distribution of Mono therapy of antihypertensive agents in hypertensive patients- Out of a total of 455 patients 212 patients were taking mono therapy; 101 patients (22.19%) were taking Amlodipine, 80 patients (17.58%) were taking Telmisartan, 15 patients (3.29%)were taking Metoprolol, 10patients (2.19%) were taking Propranolol, 4 patients (9.0%) were taking Atenolol and 2 patients (0.43%) took Enalpril (Figure 2). Satisfaction level of mono therapy of antihypertensive agents- Patients experienced excellent (51.48%) satisfaction level of mono therapy with Amlodipine and Telmisartan (55%) (Table 4). Table 4: Satisfaction level of mono therapy of antihypertensive agents (n= 212) Drugs Level of Satisfaction Number of patients (%) Excellent Very good Good Not Satisfied Amlodipine (n=101) 52 (51.48) 28 (27.72) 16 (15.84) 5 (4.95) Atenolol (n= 4) 4 (100) Metoprolol(n= 15) 0 9 (60) 6 (40) 0 Telmisartan(n= 80 ) 44 (55) 25 (31.25) 11 (13.75) 0 Propranolol (n= 10) 7 (70) 3 (30) 0 0 Enalprile (n= 2) (100) 0 Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 4

5 Side effect profile of mono therapy of antihypertensive agents- Peripheral edema, dry cough and bradycardia were the common side effect with Amlodipine whereas dizziness was observed with Telmisartan (Table 5). Table 5: Side effect profile of mono therapy of antihypertensive agent (n = 212) Details of side effect Amlodipine (n = 101) Atenolol (n = 4) Metoprolol ( n = 15) Telmisartan ( n = 80) Propranolol ( n = 10) Enalpril (n=2) Peripheral 11 (10.89) edema Dry cough 8 (7.92) (50) Bradycardia 6 (5.94) 0 2 ( 13.33) Constipation (20) 0 Dizziness (18.75) 3 (30) 0 No side effects 76 (75.24) 4 ( 100) 13 (86.66) 65 (81.25) 5 (50) 1(50) Distribution of combined therapy of antihypertensive agents-out of total of 455 patients 243 patients were taking combined therapy; 40 patients (8.79%) were taking CCBs + Loop Diuretics, 110 patients (24.17%) were taking CCBs + ARBs, 60 patients (13.18%) were taking BBs + CCBs, 20 patients (4.39%) were taking BBS + ARBs + Diuretics, 13 patients (2.85%) were taking ACEs + BBs + CCBs (Figure 3). Satisfaction level of combined therapy of antihypertensive agents- Excellent satisfaction level was observed with CCBs on combination with other class of antihypertensive agents particularly with CCBs+ARBs (56.36%) (Table 6). Table 6: Satisfaction level of combined therapy of antihypertensive agents (n = 243) Drugs Level of Satisfaction Number of patients (%) CCB S +Loop Diuretics (n=40) CCB S +ARB(n=110) BB S +CCB S (n=60) BB S +ARB S +Diuretics (n= 20) ACE S+BB S+CC B S(n=13) Excellent Very good Good Not Satisfied 17 (42.5) 10 (25) 8 (20) 5 (12.5) 62 (56.36) 28 (25.45) 15 (13.63) 5 (4.54) 15 (25) 31 (51.66) 9 (15) 5 (8.33) 8 (40) 11 (55) 1 (5) 0 6 (46.15) 4 (30.76) 3 (23.07) 0 Side effect profile of combined antihypertensive therapy Peripheral edema, dry cough, dizziness were commonly reported with combined therapy (Table 7). Level of satisfaction in patients taking Amlodipine- In this study, frequently used drug was Amlodipine (n=380) in both mono therapy and combined therapy. Out of 380 Amlodipine users, 155 patients (40.78%) showed excellent level of satisfaction, 120 patients (31.57%) showed very good level of satisfaction, 70 patients (18.42%) showed good level of satisfaction and 35 patients (9.21%) were not satisfied (Figure 4). Co-morbid conditions with hypertension In this study we observed 325 patients (71.42%) had diabetes mellitus with hypertension, 130 patients (28.57%) had respiratory disorders with hypertension (Table 8). Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 5

6 N o o f P a tie n t s N o. o f P a tie n t s N o o f p e r s o n s N o o f P a tie n t s International Journal of Pharma Research & Review, Sept 2016;5(9):1-8 ISSN: Table 7: Side effects profile of combined therapy of antihypertensive agents (n=243) Details of side effect CCB S+Loop Diuretics BB S+CCB S (n=60) CCB S+ARB S (n=110) BB S+ARB S+ Diuretics ACE S+BB S+CCB S (n =13) (n=40) (n= 20) Peripheral (18.18) 3 (15) 0 edema Dry cough 14 (35) 16 (26.66) 10 (9.09) 2 (10) 4(30.76) Headache (3.63) 1 (5) 0 Bradycardia (1.81) 1 (5) 0 Constipation (23.07) Dizziness 18 (45) 20(33.33) Nausea No side 8 (20) 24 (40) 74(67.27) 13 (65) 8 (61.53) effect Table 8: Co morbid conditions with hypertension Disease No. of patients Diabetes mellitus 325 (71.42) Respiratory disorders 130 (28.57) M e d ic a l h is to r y o f th e h y p e r te n s iv e p a tie n ts M o n o th e r a p y o f A n tih y p e r te n s iv e a g e n ts T in g lin g s e n s a tio n C h e s t p a in H e a d a c h D iz z in e s s B lu rred vision N o h is to r ic a l d is o r d e r 0 A m lo d ip in e T elm isartan M e to p r o lo l P ropranolol A te n o lo l E n a lp r il F ig. 1 -M e d ic a l h is t o r y o f th e h y p e r t e n s iv e p a tie n t s F ig. 2 - D is t r ib u t io n o f M o n o t h e r a p y o f A n tih y p e r t e n s iv e a g e n t s in h y p e r te n s iv e p a t ie n t s C o m b in e d th e r a p y o f a n tih y p e r te n s iv e a g e n ts T o ta l a m lo d ip in e U s e r s (n = 3 8 0, in c lu d in g b o th m o n o a n d c o m b in e d th e r a p y ) E x c e lle n t V e ry g o o d G o o d N o t s a tis fie d C C B s + A R B s B B s + C C B s C C B s + L o o p d iu r e tic s B B s + A R B s + D iu r e tic s A C E s + B B s + C C B s F ig. 3 -D is t r ib u tio n o f c o m b in e d t h e r a p y o f a n t ih y p e r t e n s iv e a g e n t s 0 E x c e lle n t V e r y g o o d G o o d N o t s a tis fie d F ig. 4 - L e v e l o f s a t is f a c t io n in p a t ie n t s Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 6

7 DISCUSSION The present study highlights the drug utilization pattern of antihypertensive agents of a superspeciality hospital atnashik. The effectiveness of antihypertensive agents was compared according to minimum side effect as well as satisfaction level of the patient as indicated in earlier study. [13] The drugs which minimize elevated blood pressure with minimal side effect or which showed max satisfaction level after using were consideredthe most effective antihypertensive agents. Regarding the satisfaction level of mono therapy (n=212) of antihypertensive agents, patients showed varied degrees of satisfaction. The incidence of peripheral edema, dry cough, bradycardia and dizziness were reported. Amongst monotherapy, calcium channel blocker- Amlodipine was best effective in patients. Thismight be due to lesser complications of CCBs, high safety of the drug and its preferential use in cases with no previous antihypertensive treatment. Furthermore, Amlodipine has rapid onset of action and with availability of slow release formulations and different doses, once a day dosing is possible with smooth blood pressure control as reported in earlier study.[15]in combination therapy (n= 243) two drug combination proved to be more effective than three drug combination. Despite of side effects like peripheral edema, dry cough, dizziness, the combined therapy lowered elevated blood pressure effectively and patients did not experience any discomfort. Earlier studies showed that ACE inhibitors are more effective. On the other hand, some studies indicated that beta blockers are more effective whereas other observations reported that calcium channel blockers and Angiotensine receptor blockers are more effective..[16] Use of antihypertensives in geriatric patients and in diabetic patients with CKD suffering from hypertension have also been reported. [17,18] But in our study calcium channel blockers (Amlodipine) was reported as most effective antihypertensive agent in both mono and combined therapy. The average maintenance dose of Amlodipinei.e DDD/100 bed days is The existing current guidelines suggest that 1 antihypertensive agent is required in most patients with hypertension to reach BP goals that will effectively reduce the cardio vascular risk. Choice of combination therapy depends upon the risk factors, presence of co-morbidities like diabetes, renal dysfunction and adverse effect and tailored according to individual patient. The adequate control of blood pressure in hypertensive patients was shown to be most effective on combination of two antihypertensive drugs. CONCLUSION In this study all groups in mono therapy and combination therapy were effective in reducing blood pressure. Combination therapy was used in large proportion of patients to treat moderate hypertension, in which two drug combinations were used more. The main outcomes of the study were: i)amlodipine was reported most effective in both cases of mono therapy and combined therapy of antihypertensive patients.the DDD/100 bed day s value for Amlodipine was found to be ii)treatment rates depend on age: young hypertensive patient compared with the older age groups were less aggressively treated (with low rate of drug treatment mostly with mono therapy). iii) Treatmentintensity increased where concomitant diseases were present, while there were only minor changes in preferences of the various drug classes.iv)selected physician variables did not influence drug prescribing. ACKNOWLEDGEMENT The author is thankful to the Prin. Dr. R. S. Bhambar for permitting us to carry out the study at Apollo Hospital, Nashik. REFERENCES 1. Solanki KC, Mistry RA, Singh AP, Jadav SP, Patel NM, Trivedi HR. Drug utilization study of anti-hypertensive drugs and their adverse effects in patients of a tertiary carehospital. J ClinExp Res.2010; 1: Hansson L, Dahlof B, Gudbrandsson T, Hellsing T, Kullman S, Kuylenstierna J. Antihypertensive effect of felodipine or hydralazine when added to beta-blocker therapy. J CardiovasPharmacol, 1988; 12: Kjeldsen SE, Farsang C, Sleigh P, Mancia G. World Health Organization; International Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 7

8 Society of Hypertension WHO/ISH hypertension guidelines-highlights and Update. J Hypertens, 2001; 19: Ramsay LE. British Hypertension Society Guideline for hypertension management: Summary. Br Med J. 1999, 319: Tiwari H, Kumar A, Kulkarni KS. Prescription monitoring of anti-hypertensive drug Utilization at the Punjab University Health Centre in India. Singapore Med J, 2004; 45(3): Shankar PR, Upadhyay DK, Subish P, Bhandari RB, Das B. Drug utilisation among older Inpatients in a teaching hospital in Western Nepal. Singapore Med J. 2010; 51: Sachdeva PD, Patel BG. Drug Utilization Studies- Scope and future perspectives. Int J Pharm Biol Res.2010; 1: Patel KM, Barvaliya JM, Patel KT and Tripathi BC. Drug Utilization Pattern in Critical Care Unit in a Tertiary Care Teaching Hospital in India. J.ClinExp Res : Oslo: WHO Collaborating Centre for Drug Statistics Methodology. WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC Classification and DDD Assignment, Oslo: WHO Collaborating Centre for Drug Statistics Methodology. WHO Collaborating Centre for Drug Statistics Methodology. ATC index with DDDs, ATC/DDD Methodology: History. WHO Collaborating Centre for Drug Statistics Methothodology. 12. WHO Collaborating Center of Drug Statistic Methodology. Guidelines for ATC classification and DDD assignment. Oslo, ISBN,2013; 9(8): Jaiprakash H, Vinotini K, Vindiya, Vsalni, Vikneshwara, Vigneswaran, Vinosha, Min CV. Drug Utilization Study of antihypertensive drugs in a clinic in Malaysia.Int J Basic ClinPharmacol 2013; 2(4): Ushadevi KH, Rubiya S, Vigneshwaran E, Padmanabha YR. Drug use evolution of Antihypertensive medications in outpatients in a secondary care hospital. Asian J. Pharm. Clin Res. 2013; James PA, Oparil S, Carter BL, et al. Evidencebased guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth JointNationalCommittee(JNC8).JAMA.2014;3 11: Mancia G, Fagard R, Narkiewicz K, et al. ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens,2013; 31: Atlaf M, Rasheed A, Mujtaba A, Shaik M. Drug utilization evaluation of antihypertensives in geriatric patients in a tertiary care hospital. Int.J.Pharmacy and Pharmaceutical sciences. 2014; 6(9): Elhami E, Nagaraju K. Drug Utilization Evaluation of antihypertensive drugs in diabetic patients with CKD. World J Pharmacy and Pharmaceutical Sciences. 2015;4(11): Mahalaxmi Mohan et.al, IJPRR 2016;5(9) 8