DRUG UTILIZATION EVALUATION OF ANTIHYPERTENSIVE DRUGS IN DIABETIC PATIENTS WITH CKD

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1 WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Elhami et al. SJIF Impact Factor Volume 4, Issue 11, Research Article ISSN DRUG UTILIZATION EVALUATION OF ANTIHYPERTENSIVE DRUGS IN DIABETIC PATIENTS WITH CKD Elahe Elhami* and Kiran Nagaraju *Pharm D Student, Visveswarapura Institute of Pharmaceutical Sciences, Bangalore. Assistant Professor, Department of Pharmacy Practice, Kempegowda Institute of Medical Sciences (KIMS) Hospital and Research Centre, Bangalore. Article Received on 27 Aug 2015, Revised on 16 Sep 2015, Accepted on 06 Oct 2015 *Correspondence for Author Elahe Elhami Pharm D. Student, Visveswarapura Institute of Pharmaceutical Sciences, Bangalore ABSTRACT Background: High blood pressure, or hypertension, is a major factor in the development of kidney problems in people with diabetes. Both a family history of hypertension and the presence of hypertension appear to increase chances of developing kidney disease. Objective: To determine the drug utilization evaluation of antihypertensive drugs in diabetic patients with CKD in a department of Nephrology, KIM s hospital, Bangalore. Method: Retrospective observational study was conducted from March 2010 to August 2015 in 120 renal failure patient admitted to General Medicine at KIMS hospital, Bangalore. Information from the case sheets was retrieved into a well designed data collection form from diabetic patients with CKD. Results: Out of 120 diabetic patients with CKD, 70 (58.33) were male and 50 (41.66%) were females with mean age of 53.10±11.27 years. In the enrolled patients, we found that a total of 30patients (36%) were on monotherapy, 60 (50%) on two drug therapy, 24 (20%) on three drug therapy. The most common drug prescribed was ACE follow by diuretics drugs. About 66.66% of the prescribed drugs where from Essential Drug List (EDL) In our study only 34.21% patients were prescribed generic names. Conclusion: about (39.78%) of the patients are been prescribed with ACEI s in accordance with the JNC _7 guideline. and most of drugs were found to be rational and it also shows the management of hypertension in DM patients with CKD needs combination therapy. KEYWORD: Antihypertensive drug, CKD, drug utilization evaluation, JNC _7. Vol 4, Issue 11,

2 INTRODUCTION Hypertension affects about 20-60% of patients with type-2 diabetes. [1] Serious cardiovascular events are more than twice likely in patients with diabetes and hypertension than either disease alone. [2] Each year in the United States, more than 100,000 people are diagnosed with kidney failure, a serious condition in which the kidneys fail to rid the body of wastes. [3] Kidney failure is the final stage of chronic kidney disease (CKD). Diabetes is the most common cause of kidney failure, accounting for nearly 44 percent of new cases. [3] Even when diabetes is controlled, the disease can lead to CKD and kidney failure. Most people with diabetes do not develop CKD that is severe enough to progress to kidney failure. [4] High blood pressure, or hypertension, is a major factor in the development of kidney problems in people with diabetes. Both a family history of hypertension and the presence of hypertension appear to increase chances of developing kidney disease. [5] Hypertension can be seen not only as a cause of kidney disease but also as a result of damage created by the disease. As kidney disease progresses, physical changes in the kidneys lead to increased blood pressure. Therefore, a dangerous spiral, involving rising blood pressure and factors that raise blood pressure, occurs. Early detection and treatment of even mild hypertension are essential for people with diabetes. [5] The seventh report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC) stated that angiotensin converting enzyme inhibitors (ACE-I) is an important component of most regimens to control BP in diabetic patients. [4] In these patients, ACE-I may be used alone, but are much more effective when combined with thiazide type diuretic or other antihypertensive drugs. The JNC seventh report recommended that the BP in diabetics should be controlled to levels of 130/80 mmhg or lower. Rigorous control of BP is paramount for reducing the progression of diabetic nephropathy to end-stage renal disease (ESRD). In hypertensive patients with chronic kidney disease (CKD), defined as a glomerular filtration rate (GFR) < 60 ml/min, the JNC seventh report recommended a goal BP of 130/80 mmhg and a need for using more than one anti-hypertensive drug to achieve this goal. [6] OBJECTIVES To evaluate the utilization of antihypertensive drugs in diabetic patient with chronic kidney disease (CKD) at KIMS hospital Bangalore, To determine the number of antihypertensive drugs prescribed; To determine the number of antihypertensive drugs prescribed in Generic name; To determine the number of antihypertensive drugs prescribed belong WHO essential Vol 4, Issue 11,

3 list; To Compare the prescribing pattern of antihypertensive drugs in diabetic patients with chronic kidney disease (CKD) with seventh report of the Joint National(JNC7) guideline. MATERIALS AND METHOD A Retrospective observational study was conducted from March 2010 to August 2015 in 120 diabetic patient with CKD admitted to General Medicine at KIMS hospital, Bangalore. Inclusion criteria: Age > 35 years old, diabetic patients with chronic kidney disease of both sex attending medicine unit and nephrology unit, without any CVS complication. Exclusion criteria seriously ill patients requiring ICU admission and Drug poisoning. METHODS We used the medical records of the patients to obtain diagnostic information, demographic information, and laboratory test result, (such as serum creatinine and random blood sager, FBS HBA1C, PPBS, GRBS), drug therapy used etc. Data were collected retrospectively for the period March 2010 to August 2015 and were noted in the structured case record form by the researcher All patients with HTN and DM with CKD seen during the study period were analyzed. Non target BP was defined as greater than or equal to 130/80mmHg, according to the JNC seventh report. Reduced renal function or renal impairment was defined as creatinine clearance (cr cl) < 60 ml/min. Creatinine clearance was calculated using Cockcroft_Gault equation. Total number of antihypertensive drugs Different classes of drugs used in treatment of various hypertension ailments based on WHO Essential drug Indicators. Generic vs. brand names antihypertensive drugs were noted. RESULT Table 1: Demographic data and clinical characteristic of study population (n=120) Out of 120 patients, 70 (58.33) were male and 50 (41.66%) were female. The mean age of DM patients with CKD in our study population was 53.10±11.27 years among our study population the greatest numbers of DM patients with CKD were in the age group of years 63(52.20%). The most recently recorded values of systolic, diastolic BP and random blood glucose level were 13.66±1.49; 87.66±8.49; ±23.36 mg/dl respectively. The mean serum creatinine of the patients was 35.46±14.39 ml/min. Vol 4, Issue 11,

4 Table 1: Demographic data and clinical characteristic of study population (n=120). Parameter Range Patients (%) Mean +- SD Age ±11.27 Sex Female 50(41.66) Male 70(58.33) Creatinine clearance GFR30-59ml/min GFR15-29ml/min GFR<15ml/min 80(66.66) 30(25) 10(8.33) SBP <130or =130 40(33.33) (mmhg) >130 80(66.66) DBP <80or=80 40(33.33) (mmhg) >80 80(66.66) RBS <200mg/dl 85(70.83) >200mg/dl 35(29.16) Table 2: out of 228 drugs prescribed for 120 diabetic patient with CKD, out of 228 drugs prescribed for 120 patients, most common drugs were 90(39.78%) enalapril follow by 53(23.42%) hydrochlorothiazide, 15(6.58%) torsemide, 15(6.58%) verapamil, 14(6.13%) furosemide, 11(4.82%) losartan, 10(4.38%%) bisoprolol, 9(3.94%) metoprolol, 5(2.17%) amlodipine, 6(2.63%) prazocin. Table 2: Overall patterns of use of antihypertensive drugs prescribed in diabetic patients with CKD. Drug groups Frequency Percentage% DIURETICS FUROSEMIDE 14 (6.13%) TORSEMIDE 15 (6.60%) HYDROCHLOROTHIAZIDE 53 (23.42%) ACE INHIBITOR ENALAPRIL 90 (39.78%) CALCIUM CHANNELBLOCKERS AMLODIPINE 5 (2.17%) VERAPAMIL 15 (6.58%) BETA ADRENERGIC BLOCKERS BISOPROLOL 10 (4.38 %%) METOPROLOL 9 (3.94%) ALPHA ADRENERGIC BLOCKERS PRAZOCIN 6 (2.63%) ARE INHIBITOR LOSARTAN 11 (4.82%) TOTAL 228 (99.99) Vol 4, Issue 11,

5 Table3: distribution and pattern of antihypertensive therapy in diabetic patients with CKD: Out of 120 patients were prescribed a total of 228 anti hypertensive drugs, an average of 2.45±0.91 drugs per prescription. a total of 30patients (36%) were on monotherapy, 60 (50%) on two drug therapy, 24 (20%) on three drug therapy. ACE was the most commonly (55.55%) prescribed drug class as monotherapy 30(50%) hydrochlorothiazide + enalapril, follow by torsemide+ enalapril 15(25%) were the most commonly prescribed two-drug combination therapy in patients, hydrochlorothiazide + enalapril + verapamil 15(62.50%), follow by furosemide + metoprolol + prazocin 6(25%) were the most commonly prescribed three-drug combination therapy in patient. Table3: pattern of antihypertensive therapy in diabetic patients with CKD. DRUG CLASS NUMBER OF PATIENTS PERCENTAGE% MONOTHERAY30 (36%) ACE INHIBITOR ENALAPRIL % ARE INHIBITOR LOSARTAN % DIURETICS HYDROCHLOROTHIAZIDE % TOTAL % TWO DRUG THERAPY60 (50%) HYDROCHLOROTHIAZIDE+ ENALAPRIL 30 50% TORSEMIDE+ ENALAPRIL 15 25% FUROSEMIDE+AMLDOPINE % ENALOPRIL+BISOPROLOL % TOTAL % THREE DRUG THERAPY24 (20%) HYDROCHLOROTHIAZIDE+ENALAPRIL+VER APAMIL % FUROSEMIDE+METOPROLOL+PRAZOCIN 6 25% FUROSEMIDE+LOSARTAN+MEROPROLOL % TOTAL % Table 4: distribution of drugs based on brand and generic usage: In our study out of 228 drugs prescribed, drug prescribing by brand names150 (65.78%) was more than prescribing by generic name 78(34.21%). Table 4: distribution of drugs based on brand and generic usage: DRUG PRESCRIBED NUMBER OF DRUGS(N=228) PERCENTAGE% GENERIC NAME % BRAND NAME % total Vol 4, Issue 11,

6 Table 5: prescription pattern of anti hypertension drugs according to essential drug list 2015: Out of 120 patients in our study 80(66.66%) patients prescribing according to essential drug list Table 5: prescription pattern of anti hypertension drugs according to essential drug list Antihypertension drugs Frequency Percentage% Essential drug list % Total 120 Table6: co morbidity condition: Among the 120 patients studied, there were a total of 367 coexisting illnesses such as hypertension 80 (66.66%), CKD 120(100%), cardiac disease100 (83.33%), foot ulcer 10(8.3%), cellulitis 17(14.16%), neurological disorders 13(10.83%) and anemia 27(22.5%). Table6: co morbidity condition COMORBIDITY CONDITION NUMBER OF PATIENTS PERCENTAGE (%) HYPERTENSION % CKD % CARDIAC DISEASE % FOOT ULCER % CELLULITIS % NEUROLOGICAL DISORDERS % ANEMIA % DISCUSSION This study investigated the patterns of antihypertensive drug therapy in diabetic hypertensive patients with CKD. This study showed that 80 (66.66%) of the total patients had (GFR30-59 ml/min) and 30(25%) of patients had (GFR 15-29ML/MIN) and 10(8.33%) of patients had GFR (<15 ml/min). This study revealed that 36% of the total patients were on single drug therapy, 50% were on two drugs, 20% were on three drugs therapy which differs from study done by shah J et al., where monotherapy was prescribed to 76%, 2 drugs were given to 22%, 3 drugs 2%. [7] ACEI was the most commonly prescribed drug class both in mono and combination therapy. The reported mono and combination use of ACEI was (39.78%) % which is lower than that reported by shah J et al., in treating diabetic hypertensive patients. [7] ACEI prevents microvascular complications and can prevent progression of renal damage and also ESRD in addition to lowering BP. [6] Thus our practice coincides very well with evidence base JNC 7guideline. Diuretic ranked second followed by calcium channel blocker Vol 4, Issue 11,

7 and ARE inhibitor when considering overall utilization of various antihypertensive drugs which differs from results of study done by shahj et al where CCB was second most frequently prescribed drug followed by beta blocker and diuretic. [7] Most commonly prescribed combinations were30 (50%) hydrochlorothiazide + enalapril, follow by torsemide + enalapril15 (25%) were the most commonly prescribed two-drug combination therapy in patients, hydrochlorothiazide + enalapril + verapamil15 (62.50%), follow by furosemide+ metoprolol + prazocin6 (25%) were the most commonly prescribed three-drug combination therapy in patients The combination of this drug provides added advantage because of different drugs have a different mechanism of action for reduction in blood pressure. They are also beneficial in nullifying adverse effects of each other as tachycardia caused by beta blocker is counteract by beta blockers. [8] ACEI and thiazide combination is pharmacologically favourable since it produces an additive anti hypertensive effect and minimizes most adverse effects of either the ACEI or the diuretics, especially hypokalemia. [9] Even guidelines also suggests that patient with chronic kidney disease should receive ACEI/ARB in combination with diuretic. The importance of the diuretic agent was also emphasized by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack. [10] Prescribing by generic name allows flexibility of stocking and dispensing of various brands of a particular drug that are cheaper and are as effective as proprietary brands. This is the basis of essential drug list use. [11] The percentage of generics prescribed in our study (34.21%) is very low and the drug use from essential drug list was 66.66%. This study has certain limitations like patients were not followed up for the gathering detailed and long term information on BP control achieved and occurrence of complications. Moreover the sample size was also small. Larger studies involving different age groups and large number of patients are required to implement these findings to general population of India. In our population the risk of cardiac disease were more follow by hypertension disease. CONCLUSION The prescriptions analysed were in according to guidelines of JNC _7 and most of drugs were found to be rational and it also shows the management of hypertension in DM patients with CKD needs combination therapy. Vol 4, Issue 11,

8 REFRENCE 1. Arauz-pacheco C. The treatment of hypertension in adult patients with diabetes. Diabetes Care, January 2002; 25(1): Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK prospective diabetes study group. BMJ, 1998; United States Renal Data System. USRDS 2007 Annual Data Report. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics, Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, What is kidney disease of diabetes: External. 6. Seventh report of the Joint National committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Hypertension, 2003; 42(6): Shah J, Khakhkhar T, Bhirud S, et al., Study of utilization pattern of anti-hypertensive drugs in hypertensive diabetic patients with or without reduced renal function at tertiary care teaching hospital. (IJMSPH), 2013; 2(2): Harrison. Hypertensive Vascular Disease. In: Dr. Fauci's and Dr. Longo's (eds.) Harrison's Principles Internal Medicine. 18th ed. United States: The McGraw-Hill Companies, 2008; Ishimitsu T, Yagi S, Ebihara A, Doi Y, Domae A, Shibata A. Long term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension. Jpn Heart J, 1997; 38: Major outcomes in high risk hypertensive patients randomized to angiotensin-converting enzyme inhibitors or calcium channel blockers vs diuretics: The antihypertensive and Lipid- Lowering Treatment to prevent Heart Attack Trial (ALLHAT). JAMA, 2002; 288: patel k.p, patel b, oza b, et al., pattern of antidiabetic drugs use in type-2 diabetic patients in a medicine outpatient clinic of a tertiary care teaching hospital. ijbcp., 2013 july-aug; 2(4): Vol 4, Issue 11,