A Cross-Sectional Study To Evaluate age and Gender Related Differences in Drug Utilization in Ischemic Heart Disease at a Tertiary Care Hospital

Drug utilization study is a powerful exploratory tool to evaluate the present trends of drug prescribing and appropriateness of prescription. To analyse the age and gender related differences in utilization of different classes of drugs in patients for Ischemic heart disease (IHD) management. This cross-sectional observational study was conducted from August 2017 to March 2018 in Cardiology department, PMSSY, BMC&RI, Bengaluru. The demographic, and drug prescription data of IHD patients were analyzed according to age group (18–59 years versus e” 60 years) and gender wise. Out of 520 patients diagnosed with IHD, 68% were male patients and 60% were aged e” 60 years. The most common co-morbid condition was Hypertension (66%) and was significant in patients aged e” 60 years (P= 0.0033). Anti-platelet drugs (100%) followed by Lipid lowering drugs (96%) were most commonly prescribed. The average number of drugs per prescription was found to be 6.44. Prescription of Dual anti-platelet therapy was found to be significant among men (<0.0001). Prescription of Diuretics (p = 0.045) and Pregabalin (p = 0.031) were significantly higher among females and Prescription of Angiotensin receptor blockers (ARBs) was significantly higher among those aged 18–59 years. Hypertension and Diabetes Mellitus were the most common co-morbidities observed with IHD. ARBs, Diuretics, Proton pump inhibitors, Anti Diabetic Agents and Pregabalin showed significant differences in the drug utilization with respect to age and gender. Dual anti-platelet therapy was observed to be significantly higher among males. This study has been registered in CTRI (CTRI/2018/05/013949).

World Health Organization (WHO) defines Drug utilization research as the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences. 1 It is a powerful exploratory tool to evaluate the present prescribing trends of drug use and to check the appropriateness of prescription. It helps in the management of drug specific problems thereby improving medication quality and patient safety.
Ischemic heart disease (IHD) is a condition in which there is an inadequate supply of blood and oxygen to a portion of the myocardium; it occurs due to an imbalance between myocardial oxygen supply and demand. 2 3 Men are more likely to suffer from angina pectoris and myocardial infarction at an early age as compared to women. 4,5 Co-morbidities associated with IHD and prescription of Hypolipidemics and Anti-hypertensives are observed to be more among men as compared to women. 6 Due to the differences in disease prevalence and also in co-morbidities among different age groups and gender variation, this study was taken up to observe the prescribing trend among stable IHD patients and to help in adequate drug procurement, rational usage and also to provide relevant and useful feedback to physicians.

Aims and Objectives
To analyze the age and gender related differences in utilization of different classes of drugs in out-patients for Ischemic heart disease management.

MATERIALS AND METHODS
The study was conducted between August 2017 to March 2018 at Cardiology department, Super-speciality hospital (PMSSY) attached to BMC&RI, Bengaluru among 520 out-patients diagnosed with IHD.

Study design -Cross-sectional observational study
After obtaining clearance and approval from the Institutional Ethics Committee, (Reference number: BMCRI/PS/56/2017-18) the out-patients diagnosed with IHD by the cardiologist, of either gender aged >18 years and willing to give written informed consent were included and patients diagnosed with other than IHD as their primary diagnosis were excluded from the study.
Their demographic data, history, clinical examination findings and reports of various investigations of every out-patient with IHD were recorded. The relevant data on drug prescription like number of drugs, dosage form, dose, route, time of administration, duration and frequency of drugs prescribed to each patient was recorded.
Drugs were classified based on WHO's Anatomic Therapeutic Chemical (ATC) classification system. They were divided into groups based on Anatomical main group (1 st level), Therapeutic, Pharmacological and Chemical characteristics (2 nd , 3 rd and 4 th levels). The total number of drugs, cardiovascular drugs and noncardiovascular drugs prescribed per person was noted. The age and gender related differences were analyzed based on the prescription of cardiovascular drugs and non-cardiovascular drugs. The characteristics of IHD patients was analysed to identify potential factors affecting utilization of cardiovascular drug classes.

Statistical analysis
The descriptive data in this study was analysed using mean, Standard deviation, percentage and proportions. Chi square test and Mann-Whitney U test was appropriately used to compare characteristics between the genders (male versus female), and between the age groups (18 -59 years versus > 60 years). A p-value of < 0.05 was considered to be statistically significant.
In our study, age and gender related differences was not observed in b-blockers, ACEIs and CCBs. Prescription of Diuretics (p = 0.045) and Pregabalin (p = 0.031) were significantly higher among females. Prescription of ARBs were significantly higher among those aged 18-59 years (p = 0.012) and PPIs was significantly higher among those aged > 60 years (p = 0.049). Anti Diabetic agents prescription was significantly higher among those aged > 60 years (p = 0.033) and in male patients aged > 60 years. Among the anti-platelets prescribed, dual anti-platelet therapy was found to be significantly higher among males (p < 0.0001). (Table 7) There was a significant difference in prescription of Cardiovascular drugs when compared to non-cardiovascular drugs with respect to age and gender (p < 0.0001) ( Table 8).

DISCUSSION
This study was aimed at identifying age and gender related differences in drug use among patients with IHD along with co-morbid illness. Drug prescribing practices will aid in drug procurement and provide feedback to treating physician in rational prescribing.
During the study period, among 520 prescriptions, male preponderance (60%) was observed and was in accordance with other studies 3,7,8,9 , indicating that IHD is slightly more    Among the co-morbid illness, age and gender differences were noted in the prevalence of HTN and T2DM as it was significantly greater among males patients aged > 60 years. Therefore utilization of Anti-diabetics followed the same trend as Anti-hypertensives.
In our study we observed that HTN was the most common co-morbidity and significantly higher among patients aged > 60 years (p = 0.0003) and males aged > 60 years (p = 0.0006) which was in accordance with previous studies. 3,7,8,9 Shruthi D et al 3 in her study observed Type 2 Diabetes Mellitus in 38% patients with IHD similar to our study (38%). Hence Anti Diabetic agents prescription was significantly higher among those aged > 60 years (p = 0.033) and in male patients aged > 60 years.
The mean age was 57.7 years similar to study conducted by Zachariah et al 9 with 56.9 years. Very little difference in the two age groups was noted which was similar to study conducted by Kunnoor N et al 7  In our study, for the treatment of IHD, various cardiovascular drugs namely Antiplatelet drugs, Anticoagulants, Anti-anginal drugs, Lipid modifying agents, b -blockers, Angiotensin converting enzyme inhibitors (ACEIs), Angiotensin II receptor blockers (ARBs), Calcium channel blockers (CCBs), Diuretics, and non -cardiovascular drugs -Anti Diabetic agents, Proton Pump Inhibitors, calcium, Pregabalin, Iron preparations, Nutraceuticals were prescribed.
Most of the drugs prescribed in our study were in accordance with AHA/ACC guidelines for treatment of stable IHD. In our study the commonly prescribed drugs were Aspirin among Anti-platelet drugs, Atorvastatin among Lipid lowering drugs, Ramipril among ACEIs, Telmisartan among ARBs, Metoprolol among b-blockers and Amlodipine among CCBs and these drugs were freely available in our hospital pharmacy.
In our study higher rates of utilization of Anti-platelet drugs and Lipid lowering drugs were observed irrespective of age and gender which was similar to previous studies. 3,10 Dual Anti-platelet Therapy (DAPT) prescription was found to be significantly higher among males (<0.0001) which was contradictory to results obtained by Jyothi et al in a retrospective study conducted among IHD patients and observed that females were more commonly prescribed. (11) DAPT was more effective than aspirin monotherapy in reducing ischemic events (7.3% DAPT vs. 8.8% aspirin, p = 0.01) among IHD patients, at the cost of increased bleeding (2.0% DAPT patients vs. 1.3% aspirin patients, p=0.004) which was observed in a study conducted by Bhatt DL et al. 12 There was a significant difference in prescription of Cardiovascular and noncardiovascular drugs with respect to age and gender (p < 0.0001) this difference was not observed in study conducted by Kunnoor N et al 7 Prescription of Diuretics (P=0.045) was significantly higher among females, but this observation did not correlate with the study done by Kunnoor N et al 7 In our study, higher rates of utilization of Diuretics may be due to higher rates of heart failure among females but this data was not recorded and it was one of the limitations of our study.
The utilization of ACEIs and ARBs in male patients was not significantly different from their use in female patients (46% vs. 45.7%; p = 1 and 32.7 vs. 37.5; p = 0.35 respectively) similar to the study done by Kunnoor N et al 7 Prescription of Angiotensin receptor blockers was significantly Use of ACEIs has beneficial effects against Fibrosis and cardiac remodelling thereby decreasing morbidity and mortality in IHD.
In our study there was no significant difference in Utilization of â-blockers with respect to age and gender. Metoprolol was the most commonly prescribed beta blocker followed by Carvedilol. Kunnoor N et al 7 observed a significant higher prescription of â-blockers (p = 0.015) among patients aged 18 -59 years and those aged > 60 years.
Kunnoor N et al. observed a significantly higher use of CCBs in male patients aged > 60 years similar difference was observed in our study but it was not statistically significant (p = 0.07 ). The 2011 NICE guidelines recommend use of CCBs in patients aged > 55 years and ACE-Is in patients aged < 55 years 13 In our study there were no age and gender differences in Utilization of Anti-anginal drugs (Vasodilators) similar to the study done by Kunnoor N et al 7 Differences in number of drugs per prescription (< 5 and > 5) were analyzed according to age and gender but the difference was not statistically significant.
No differences in the prescription of cardiovascular drugs were observed with respect to age and gender. A significant difference in the prescription of Non -Cardiovascular drugs was observed between patients aged 18 -59 years and groups similar to study by Kunnoor N et al 7 Patients were stratified into 3 groups based on the duration of IHD i.e., < 1 year , 1 -5 years and > 5 years and we observed a significant differences between the groups (p = 0.0066) among patient aged > 60 years.
Strengths -This is one of the few studies conducted to analyze age and gender related differences in IHD. The findings of the present study clearly highlight the need for patient age to be taken into consideration when initiating pharmacotherapy for IHD, especially among outpatients who consume drugs for life long.
Limitations -Associated indications like Heart failure and Left ventricular dysfunction was not considered. Other modifiable risk factors like smoking, obesity, lifestyle and lipid profile of the patient was also not taken into consideration during assessment in our study. A prospective study with larger sample sizes among inpatients and adequate data on Adverse Drug Reactions monitoring is recommended to accurately estimate the age and gender-related differences in drug use in IHD at a tertiary care setting. The result of this study cannot be generalized since the study was conducted in a super-specialty set up of a tertiary care hospital among homogenous population.

CONCLUSION
HTN and DM were the most common comorbidities observed with IHD. ARBs, Diuretics, PPI, ADAs and Pregabalin showed significant differences in the drug utilisation with respect to age and gender. Dual anti-platelet therapy was observed to be significantly higher among males.