Review of Global Medicine and Healthcare Research Volume 2 Number 2 (211) Publisher: DRUNPP Managed by: IOMC Group Website: www.iomcworld.com/rgmhr/
Drug Utilization Pattern and Co-morbidtities Among Hypertensive Patients in Sub-Urban Hospital, Malaysia Baig MR 1, Shih Yuit W 1, Ramani M 1, Chia Jin P 1, Asma M 2, Tahir MK 3 * 1 Department of Pharmacy, Asian Institute of Medical Sciences, 81, Bedong, Kedah Darul Aman, Malaysia 2 Chief Pharmacist, Hospital Sultan Abdul Halim, Sungai Petani Malaysia 3 College of Clinical Pharmacy, King Faisal University, Alahsah, Kingdom Of Saudi Arabia * Corresponding author; Email: tahir.pks@gmail.com ABSTRACT Background: To reach an optimum blood pressure level among hypertensive patients, combinations of two or more antihypertensive drug classes may be needed. Objective: This study aimed to describe the drug utilisation pattern of anti-hypertensive agents in sub-urban government hospital, Hospital Sultan Abdul Halim, Sungai Petani, Malaysia. Methodology: A cross-sectional retrospective evaluation of prescription was done from 3 March 29 to 19 June 29. Data analysis was conducted using Statistical Package for Social Sciences (SPSS) software version 13.. The chi-square test was used to determine the differences between proportions. Odd rations were calculated to identify the groups at higher risk of co-morbidities. Results: A total of 5 hypertensive patient s prescriptions were screened for the study, in which 288 (57.6%) were males and 212 (42.4%) were females. The most common comorbidity found in these hypertensive patients were cardiac disease (39.8%), followed by diabetes mellitus (38%) with nephropathy. The male patients were with high risk of comorbidities. Polytherapy was found to be the most preferred prescribing pattern, 318 (63.6%) patients were given polytherapy, while 182 (36.4%) patients were given monotherapy. Beta blocker (BB), 242 times (48.4%) is the highest prescribed drug class followed by angiotensinconverting enzyme inhibitors (ACEI), 235 times (47.%); calcium channel blockers (CCB), 218 times (43.6 %); diuretics, 146 times (29.2%); and the least prescribed drug is alpha blockers, 15 times (.3%). An increase of 42.3% was found in antihypertensive drug consumption in hospital from 21 to 29. Conclusion: The study shows Polytherapy is the most preferred prescribing pattern for treating hypertension in Hospital Sultan Abdul Halim when compared to the use of a single type of antihypertensive drug, monotherapy. The use of beta blockers and short-acting preparations were commonly used both as monotherapy and combination treatment. Overall therapy was not found complaint with the Malaysian guidelines for the management of hypertension. Keywords: Drug utilisation, Anti-hypertensive agents, Diabetes mellitus, Beta blocker, Angiotensin-converting enzyme inhibitors, Malaysian guidelines Vol. 2 No 2 (211) Page 139
Introduction Among the developed nations like U.S there are more than 7 million adults with confirm diagnosis of hypertension [1] which latter put an addition burden due to serious adverse cardiovascular and cerebrovascular events, including myocardial infarction (MI), angina pectoris, stroke, and renal disease [2]. These risks can be avoided by the proper management of hypertension. Commonly used anti-hypertensive agents are thiazide-type diuretics such as hydrochlorothiazide (HCTZ), angiotensin-receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel blockers. 3 Mono therapy is more affective at initial stages however, in most of the case a combination therapy is recommended to control hypertension [2, 3]. It is seen that in developed countries, only 27% of hypertensive on treatment had adequate blood pressure control i.e below 14/9 mmhg [4]. The scenario is worse in developing countries [5]. In Malaysia a review from the Information and Documentation System Unit of the Ministry of Health of Malaysia showed that cardiovascular disease had been the principal cause of death in government hospitals over the years, accounting for 23% to 26% of deaths from 1994 to 21. Cardiovascular disease is the major cause of hospital admissions and death in government hospitals in Malaysia. The National Health and Morbidity survey showed 61% of Malaysians had co-morbidity along with hypertension. The prevalence of hypertension in Malaysians aged 3 years and above was 42.6% in 26 [6]. The choice of anti hypertensive drug class patients is influenced by, many factors like the presence of multiple co-morbid conditions and the possibility or risk of drugdrug interactions. To reach an optimum blood pressure level in these patients, combinations of two or more antihypertensive drug classes may be needed. This study aimed to describe the pattern of use in a sub-urban government hospital, its compliance with guidelines, and its economic impact. Vol. 2 No 2 (211) Page 14
Methodology A cross-sectional retrospective evaluation of prescription was done for the patients attended Hospital Sultan Abdul Halim, Sungai Petani. - Study Duration: The study was conducted from 3 March 29 to 19 June 29. - Study Design: A retrospective study was conducted based on the availability of the prescription forms of the patients with diagnosis of hypertension. A standard data collection form was developed and validated by a group of a Pharmacist; Medical Doctor and a Professor. The data form was designed in such a way that it collects the information about the patient s demographic characteristics and drug utilization pattern, which includes age, gender, race, indication, dosage of commonly prescribed antihypertensive drugs in the Hospital. Sampling Method: All the information was collected with the permission of the director and the ethical committee of the state with the supervision of the concern Pharmacist. This research is registered in Clinical Research Centre (CRC) with a government approval. Sample sizes of 5 prescription forms of patients with hypertension were selected. Convenience sampling technique was employed for the selection of patients. Information was analyses based on data regarding race, age, gender, indications and trends in the prescribing of antihypertensive medications at Hospital Sultan Abdul Halim, Sungai Petani. Data analysis was conducted using Statistical Package for Social Sciences (SPSS) software version 13.. The chi-square test was used to determine the differences between proportions. Odd rations were calculated to identify the groups at higher risk of co-morbidities. Results A total of 5 patients prescription was collected. The patients receiving medications for antihypertensive agent were 288 (57.6%) males and 212 (42.4%) females. The age Vol. 2 No 2 (211) Page 141
distribution of 5 patients studied shows that the highest number of patients receiving medication of antihypertensive agent was within the age range of 51-6 years having 166 (33.2%). In terms of race majority of the patients were Malay 298 (59.6%) followed by Chinese 113 (22.6%) and 89 (17.8%) of Indian (Table 1). In most of the case the patients have other medical complications in addition to hypertension. Majority, 199 (39.8%) were with cardiac disease like; angina, Myocardial infraction and ischemic heart diseases followed by Diabetes Mellitus patients and renal failure. Details are described in Table 1. However, the prevalence of comorbid diabetes mellitus was significantly higher among Malays than Chinese and Indians (Table 2). In terms of gender, men were more like to be at the risk of cardiac complications (OR 1.335 [CI 1.153-1.545]) and renal failure (OR 1.128 [CI.788-1.616]). While female were found at higher risk of diabetes mellitus (OR 1.114[CI.96-1.369]). About 318(63.6%) patients were on treatment with poly-therapy for hypertension while rest were treated with mono-therapy. Beta blockers (BB) were the most frequently prescribed drugs for antihypertensive treatment. Those receiving antihypertensive therapy, the most frequently prescribed drug types were, metoprolol 161(32.2%); perindopril 154(3.8%); amlodipine 98(19.6%); atenolol 67(13.4%); frusemide 66(13.2%); captopril 59(11.8%); vastarel 58(11.6%); felodipine 57(11.4%); chlorthiazide 42(8.4%); nifedipine 4(8.%); and the least are carvedilol, losartan, ramipril, terazosin 2(.4% each); and doxasin 1(.2%). Details about the various anti-hypertensive agents used are shown in Table 3. Discussion Findings of the current study demonstrate that the most frequently prescribed antihypertensive drug class were Beta-Blockers (48.4%). In about n=37 cases it is used as a single therapy however, in n=25 it is used in combination with other antihypertensive drugs. Unlike the finding of [1] the use of ACEI, CCBs, Diuretics or ARBs was found least in our study. BB was observed to be most commonly prescribed regimens. These finding are not in Vol. 2 No 2 (211) Page 142
compliance with the findings of [1]. Moreover, the compliance level to the Malaysian clinical practice guidelines for the treatment of hypertension was also low, which prefer the use of ACEI, CCBs, Diuretics or ARBs as first line of therapy. β-blockers are no longer preferred as compelling evidence showed that they were associated with 16% increase in the risk of stroke when compared to other agents [6] and an excess cardiovascular event risk of 18% in older patients (>6years) [7] It has also been shown to increase the incidence of new-onset diabetes compared to other drugs, especially in those with high metabolic risk [8]. They were the least effective agents in terms of LVH regression [9] and reduced central aortic pressure less effectively [1] than newer antihypertensive agents. β-blockers should only be prescribed when compelling indications such as heart failure or ischaemic heart disease co exist [11]. In addition its is also seen that in about 76 (%) diabetic patients, BB were used in combination or as a single line of therapy. Evidence are there that discourage the use of BB among diabetic patients which make it difficult to predict signs and symptoms of hypoglycemia such as tremors and tachycardia may be absent, making it more difficult for patients to recognize an oncoming episode. In addition, multiple effects on glucose metabolism have been reported, usually with the noncardioselective beta-blockers (e.g., propranolol, pindolol, timolol) but occasionally also with relatively beta-1 selective agents (e.g., metoprolol). Conclusion Polytherapy is the most preferred prescribing pattern for treating hypertension in Hospital Sultan Abdul Halim when compared to the use of a single type of antihypertensive drug, monotherapy. The use of beta blockers and short-acting preparations were commonly used both as monotherapy and combination treatment. Overall therapy was not found complaint with the Malaysian guidelines for the management of hypertension. Vol. 2 No 2 (211) Page 143
References 1. Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics 27 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 27;115(5):e69 e6171. 2. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. 23;289(19):256 2572. 3. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: Analysis of 354 randomised trials. BMJ. 23;326(744):1427. 4. Colhoun HM, DongW, Poulter NR. Blood pressure screening, management and control in England: results from the health survey for England. 1994. J Hypertens 1998; 16: 752 757. 5. Murray CJL, Lopez AD (eds). The Global Burden of Diseases, Comprehensive Assessment of Mortality and Disability From Diseases, Injuries and Risk Factors in 199 Projected to 22: World Health Organisation. Harvard University Press: USA 1996. 6. Lindholm LH, Carlberg B, Samuelsson O. Should beta-blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 25;366(9496):1545-53. 4 7. Khan N, McAlister FA. Re-examining the efficacy of beta-blockers for the treatment of hypertension: a meta-analysis. CMAJ. 26;174(12):1737-42. 8. Elliot WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 27;369(9557):21-7. 9. Schmieder RE, Martus P, Klinbeil A. Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA. 1996;275(19):157-13. 1. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFÉ) study. Circulation. 26; 113(9):1213-25. 11. Malaysian Hypertension Guideline Working Group. Clinical Practice Guidelines on Management of Hypertension. 3rd ed. 28. MOH/P/PAK/156.8 (GU). Vol. 2 No 2 (211) Page 144
Table 1: Demographic and Medical information of patients Demographics N= 5 % Gender Male Female 288 212 57.6 42.4 Age of Patients Range 12-98 Year Mean age= 57±12.94 Race 11-2 21-3 31-4 41-5 51-6 61-7 71-8 81-9 >9 Malay Chinese Indian 2 9 34 9 166 14 8 13 2 298 113 89.4 1.8 6.8 18. 33.2 2.8 16. 2.6.4 59.6 22.6 17.8 Co-morbidities Heart Disease Diabetes Mellitus Renal Failure 199 19 17 39.8 38. 3.4 Number of Patient with one of Multiple Medical complication HPT+DM+CD+RD HPT+DM+CD HPT+DM+RD HPT+CD+RD HPT+DM HPT+CD HPT+RD HPT alone 1 74 5 2 11 122 9 177.2 14.8 1.4 22 24.4 1.8 35.4 Vol. 2 No 2 (211) Page 145
Table 2: Prevalence of co-morbidities as per Age and Race of the Patient Demographics Age Race 11-2 21-3 31-4 41-5 51-6 61-7 71-8 81-9 >9 Malay Chinese Indian Diabetes Mellitus N(19) 2(1.1%) 6(3.2%) 34(17.9%) 75 (39.5%) 38 (2.%) 29 (15.3%) 6(3.2%) X 2 13.581, df=8, p=<.93 15 (55.3%) 4 (21.1%) 45 (23.7%) X 2 7.253, df=2, p=.27* Cardiac Complication N(199) 5(2.5%) 26(13.1%) 67(33.7%) 55(27.6%) 39(19.6%) 7(3.5%) X 2 33.21, df=8, p=<.1* 122 (61.3%) 43(21.6%) 34(17.1%) X 2.4, df=2, p=.819 Renal Failure N(17) 1(5.9%) 2(11.8%) 2(11.8%) 2(11.8%) 5(29.4%) 4(23.5%) 1(5.9%) X 2 19.44, df=8, p=<.15* 9(52.9%) 7(41.2%) 1(5.9%) X 2 4.222, df=2, p=.121 Table 3: Various categories of antihypertensive drugs prescribed in single and combination drug therapy Drugs Single Combination ACEI ARB BB CCB DIU AB (n=235) (n=51) (n=242) (n=218) (n=146) (n=15) 65 14 37 54 12 17 37 25 164 134 15 Note: As different cases were on poly pharmacy, therefore the sum is not always 1% Vol. 2 No 2 (211) Page 146