85 P a g e International Standard Serial Number (ISSN): 2319-8141 International Journal of Universal Pharmacy and Bio Sciences 6(6): November-December 2017 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO SCIENCES IMPACT FACTOR 4.018*** ICV 6.16*** Pharmaceutical Sciences RESEARCH ARTICLE!!! THE EVALUATION OF EFFECTIVENESS OF ANTIHYPERTENSIVE AGENTS AS MONOTHERAPY OR COMBINATION THERAPY IN A TERTIARY CARE HOSPITAL Basil Sunny 1 *, Sophiya T Varghese 1, Hemalatha S 2, Sivakumar T 3 * 1 Pharm.D (Doctor of Pharmacy), Nandha college of Pharmacy. 2 Lecturer, Nandha college of Pharmacy. 3 Principal, Nandha college of Pharmacy. KEYWORDS: Hypertension, Monotherapy, JNC-8, Antihypertensive, Combination therapy. For Correspondence: Basil Sunny* Address: Nandha college of Pharmacy, Erode, Tamilnadu 638052. ABSTRACT The prevalence of hypertension varies from 17-21 percentages in all states of India according to the ICMR survey. The rates are higher in old and obese patients. Hypertension doubles the risk of cardiovascular diseases, renal diseases, stroke, and retinal diseases. Our study was conducted in a tertiary care hospital and patients with systemic hypertension above the age of 18 were included in the study. This study was carried out in order to find out the efficacy of various antihypertensive therapeutic classes. Finally therapeutic goals were defined as per JNC 8. It was seen that fixed drug combination showed highest BP control than monotherapy and free equivalent combinations.
86 P a g e International Standard Serial Number (ISSN): 2319-8141 INTRODUCTION: Hypertension can be defined as persistent increase in blood pressure to an extent that places a patient at elevated risk for target organ damage. About 75 lakhs(13-15%)and around 9 crores disability adjusted life years worldwide(daly) contributed by high BP in 2001.Hypertension doubles the risk of cardiovascular diseases like coronary vascular events, peripheral vascular disease, End stage renal disease, stroke, retinal disease(hypertensive retinopathy). According to Framingham study it has been shown that hypertensive patient have four fold increase in cardiovascular events and 6 fold increase in congestive heart failure in comparison with normotensive individuals. [1-3] Hypertension is like an iceberg disease since large segments of hypertensive population are unaware/inadequately treated/ untreated. In India as per ICMR survey (2007-2008) prevalence of hypertension was varying from 17-21% in all the states. Prevalence of hypertension is higher in old and obese patients. Other risk factors are high sodium chloride intake, low calcium and potassium intake, alcohol consumption, psychosocial stress and low level of physical activity. [1,4] As per JNC 8 the pharmacologic treatment must be initiated when For patients < 60yrs of age, start treatment if BP is 140/90 mmhg For patients with diabetes, start treatment if BP is 140/90 mmhg For patients with CKD, start treatment if BP is 140/90 mmhg For patients 60yrs of age, start treatment if BP is 150/90 mmhg For patients < 80yrs of age, start treatment if BP is 140/90 mmhg For patients > 80yrs of age, start treatment if BP is 150/90 mmhg The risk of stroke could be reduced by lowering systolic BP by 10-12 mmhg and diastolic BP by 5-6 mmhg and by 12-16% for CHF within 5 years of treatment initiation. By controlling hypertension we could minimise the rate of progression of hypertension allied kidney disease. Based of hypertension severity, age and other cardiovascular risks, comorbidities, side effects and frequency of dosing, individualization of the treatment must be done i.e. whether to prescribe combination treatment or individual drug. [5-8]
87 P a g e International Standard Serial Number (ISSN): 2319-8141 MATERIAL AND METHODS: Data source: The study was conducted in a tertiary care hospital. The data were collected from the inpatient records; which include patient demographics, height, weight, diagnosis, comorbidities, laboratory data, medical and medication history, medication dosing frequency, mean BP, reduction in BP and JNC goal attainment. Cleaning: Inclusion criteria: Patients with systemic hypertension above the age of 18 were included in the study. Exclusion criteria: Those patients with recent attack of ischaemic stroke, MI were excluded from the study. Finally therapeutic goals were defined as per JNC8.For patients without any comorbidity (DM and CKD)BP control is defined as mean systolic BP <130 mmhg and mean diastolic BP < 80 mmhg and for patients with comorbidities (DM & CKD) BP control is defined as mean systolic BP <14O mmhg and mean diastolic BP < 90 mmhg respectively. Antihypertensive agents were classified into the following therapeutic classes: ACE inhibitors, ARB Blockers, Beta blockers, Calcium channel blockers, thiazides and thiazide like diuretics.all other antihypertensive therapeutic classes were excluded due to insufficient number for adequate analysis.
88 P a g e International Standard Serial Number (ISSN): 2319-8141 RESULTS: 1. POPULATION CHARACTERSTICS DEMOGROGRAPHICS MALE 118 FEMALE 102 AGE <40 48 40-50 52 50-60 26 60-70 64 70-80 21 >80 9 COMORBIDITIES DM 68 CKD 10 TB 41 THYROID 35 CARDIAC 34 2. JNC GOAL ATTAINMENT ACCORDING TO AGE AGE GOAL ATTAINED NOT ATTAINED <40 41 9 40-50 8 42 50-60 30 0 60-70 48 12 70-80 19 1 >80 8 2
89 P a g e International Standard Serial Number (ISSN): 2319-8141 3. JNC GOAL ATTAINMENT IN PATIENTS WITH COMORBIDITIES COMORBIDITIES ATTAINED NOT ATTAINED DIABETIC 46 24 CKD 0 10 OTHERS 89 21 NO COMORBIDITIES 18 12 4. MEAN BLOOD PRESSURE MONOTHERAPY CCB B- BLOCKER ACE INHIBITORS Mean systolic BP (mmhg) 124 126.35 138 Mean diastolic BP (mmhg) 78.84 81.05 90 Goal attainment (%) 79.3 84.4 82.7 FDC CCB + DIURETIC ARB + DIURETIC Mean systolic BP (mmhg) 131.6 135 Mean diastolic BP (mmhg) 84.6 85 Goal attainment (%) 91.8 87.6 FEC CCB + DIURETIC ACE + CCB ARB + DIURETIC Mean systolic BP (mmhg) 146.5 135 142.9 Mean diastolic BP (mmhg) 89.45 82.5 92.3 Goal attainment (%) 72.1 85.2 64.6 V: GOAL ATTAINMENT BASED ON THERAPEUTIC CLASS THERAPEUTIC CLASS FEC FDC CCB + DIURETIC 72.1 91.8 ARB + DIURETIC 64.6 87.6
90 P a g e International Standard Serial Number (ISSN): 2319-8141 100 90 82.1 89.7 73.96 80 70 60 50 40 MONOTHERAPY FDC FEC 30 20 10 0 GOAL ATTAINED DISCUSSION: The population individualities for all the 220 patients who were on antihypertensive therapy are shown in Table 1. Among them 46.36 % are female patients and 53.63% are male patients. There were more geriatric patients and 86.36 % of the patients had either diabetes, TB, CKD or other comorbidities which require lower JNC blood pressure goals. This study found that patients receiving antihypertensive therapy were on 1 of the 5 antihypertensive therapeutic classes as monotherapy and showed remarkably similar average reductions in blood pressure for FDC. These results are consistent with those found in an observational study carried out by Michael R. Bronsert et al., in 2013 to compare the effectiveness of different antihypertensive therapeutic classes stated that monotherapy also had similar reductions in BP as FDC. [1] In spite of similar BP reduction among different therapeutic classes, B- blockers showed higher rates of JNC8 goal attainment in patients initiated with monotherapy followed by ACE inhibitors.
91 P a g e International Standard Serial Number (ISSN): 2319-8141 It was observed that patients who were on FDC antihypertensive treatment had substantially greater reductions in BP and higher JNC goal attainment rates than patients on monotherapy(table 4).Among FDC two combinations were selected, that is CCB + Diuretic and ARB + Diuretic and it showed 91.8% of goal attainment for CCB + Diuretic combination and 87.6% for ARB + Diuretic. A cross-sectional survey conducted by Roas S et al., on Antihypertensive combination in primary care settings indicated that patients initiated on FDC obtain better control of BP than patients initiated on monotherapy alone. [9] The patients who were on FEC tend to have lower goal attainment as compared to monotherapy and FDC. Among FEC three combinations were included in the study, which comprise of CCB + Diuretic, ACE inhibitors + CCB and ARB + Diuretic. Among them ACE inhibitors + CCB showed higher effectiveness (85.2%) as compared with CCB + Diuretic (72.1%) and ARB + Diuretic (64.6%). On analysing the JNC goal attainment based on therapeutic class for both FEC and FDC,it was found that for CCB + Diuretic 72.1% of patients have controlled BP in FEC and 91.8 % for FDC. In case of ARB + Diuretic 64.6% of patients had controlled BP in FEC and 87.6% in FDC. As per JNC8 guidelines for hypertension, patients with diabetes and CKD only require 140/90 for their goal attainment whereas for patients without comorbidities require 130/80 for the same. From this study it was found that only 46% of diabetic patients attainted their therapeutic goal whereas for CKD patients none attained their therapeutic goal. For patients without comorbidities 18% shown goal attainment. CONCLUSION: Antihypertensives continue to be one of the highly consumed drugs all over the world. Coming to the effectiveness of antihypertensive therapy JNC has launched certain guidelines for BP reduction. This study was carried out in order to find out the efficacy of various antihypertensive therapeutic classes. It was seen that FDC showed highest BP control followed by monotherapy and FEC.
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