Assessment of drug utilization pattern of antihypertensive medications using defined daily dose, drug utilization 90% and World Health Organization drug use indicators

INTRODUCTION

High blood pressure (hypertension) is a major global health problem and serves as a significant contributor to developing cardiovascular, cerebrovascular, peripheral artery disease, and kidney complications. The 2019 Global Burden of Disease data highlighted that cardiovascular disease resulted in 18.6 million deaths globally, with a marked increase in disability-adjusted life years (DALYs), indicating a substantial impact on global health statistics.¹ A wide range of antihypertensive medications are available for the treatment of hypertension. In spite of the availability of a large number of antihypertensive agents, it has been found that control of BP in the normal range in India has been achieved only in 13.64% of the hypertensive population.²

The inappropriate drug prescriptions may lead to potentially serious complications in patients. This also puts a financial burden on them, reducing compliance and increasing the risk of adverse effects. Drug utilization studies (DUS) help in a better understanding of the pattern of drug usage, adherence to guidelines, effectiveness, safety, reducing cost burden, and better patient compliance. Thus, DUS guides clinicians to enhance therapeutic outcomes and minimize inappropriate drug usage. The pattern of usage of antihypertensive medications has also undergone change from time to time, reflecting advances in our understanding of the mechanisms of underlying hypertension and the development of more effective and safer drugs.

The drug utilization patterns help healthcare workers to have an in-depth and wide understanding of drug prescription patterns, their effectiveness, and safety concerns that help them to avoid irrational prescriptions and elevate the quality of healthcare practices to benefit the broader population.^3,4 Conducting DUS at regular intervals facilitates the promotion of rational drug use and enhances the understanding of patient health indicators.

The World Health Organization (WHO) defines DUS as the study of the promoting, distribution, prescribing, and use of medications in society, with particular focus on the resulting medical, social, and economic impacts.⁵ These studies aim to promote rational drug use, ensuring appropriate prescribing, distribution, and patient use of medicines for diagnosing, preventing, and treating diseases.⁶

Different WHO drug utilization indicators and the “Anatomical therapeutic chemical (ATC)”/”Defined daily dose (DDD)” toolkit were used for assessing DUS. The ATC/DDD methodology is being used in various standard classifications of medications between countries, national health policies, pharmacoepidemiologic studies, pharmacovigilance, and drug utilization research. Each drug is given at least one ATC code, and drugs are categorized into several groups based on the organ or system they act on, and on the basis of their therapeutic and chemical properties.⁵ To facilitate comparisons of drug consumption over time and across different regions, the DDD measurement unit has also been developed along with the ATC classification system. The DDD, assigned by the WHO Collaborating Centre, represents the assumed average daily maintenance dose for a drug that is used as a primary indication in adults.

DU 90% is another simple and cost-effective tool that can be used to assess drug prescribing practices. It identifies the drugs that account for 90% of the total volume of prescribed medications, ranked by their DDD.^7,8 Thus, analysis of drug utilization patterns helps in the improvement of therapeutic effectiveness and gives valuable feedback to prescribers. This feedback further plays a guiding role for prescribers in the promotion of rational use of medicines and the minimization of adverse reactions. The aim of the current study was to examine the prescribing practices, utilization, and adverse drug responses of antihypertensive drugs in hypertension patients at an East Delhi tertiary care hospital.

MATERIAL AND METHODS

A prospective observational study was undertaken in the Pharmacology and General Medicine Departments at the University College of Medical Sciences and Guru Teg Bahadur Hospital, a tertiary care facility in East Delhi, from January 2021 to August 2022. Approval from the University College of Medical Sciences (UCMS) Institutional Human Ethics Committee (IECHR/2020/PG/46/25-R1) was obtained.

RESULTS

Out of the 150 patients that were part of the study, 62 (41.33%) were between the ages of 61 and 75, while 45 (30%) were older than 75, 34 (22.67%) patients were between the ages of 46 and 60, and 9 (6%), between the ages of 30 and 45. The mean age of patients was 67.54 ± 12.38 years. Of the patients, 77 (51.33%) were men and 73 (48.67%) were women. Additionally, 67 (44.67%) had no family history of hypertension, while 83 (55.33%) had a family history. Out of 150, 77(51.33%) patients were on antihypertensives for 0-1 year, while 73(48.67%) were on antihypertensive treatment for more than 1 year. A majority of 50(33.33%) patients had cardiovascular diseases as a co-morbidity, whereas 34(22.67%) patients had diabetes mellitus [Table 1].

A total of 876 drugs were prescribed in all the prescriptions (n=150) included for this study. The average number of drugs prescribed per encounter was 5.85. The generic name was used to write the prescription for 797 (90.98%) drugs, and an injectable dosage form was given for 10 (1.14%) out of 876 drugs. Of the 876 drugs that were prescribed, 806 (92%) were from the EDL, and 783 (89.38%) were given out by the hospital pharmacy. Of the study population, 108 patients (72%) knew the right dosage, and every patient knew the right dosage form. 84.67 % (127/150) of patients have the knowledge of the correct medication name. Every patient understood the proper way to take their prescribed drugs. In each prescription, the number of drugs prescribed ranged from one to eleven. Only one drug was prescribed in 14 (9.33%) prescriptions. The average number of antihypertensive drugs prescribed per prescription was 2.30 [Table 2].

The most common antihypertensive written in prescription belonged to calcium channel blockers (CCBs), being prescribed in 107 (31.19%) patients. Angiotensin receptor blockers (ARBs) were prescribed to 61 (17.78%) patients. Among CCB, amlodipine was the most frequently prescribed CCB in 107(71.33%) patients, while telmisartan was the most commonly prescribed drug among ARBs in 61(40.67%) patients. Fixed-dose combinations of telmisartan + hydrochlorothiazide and telmisartan + amlodipine were also prescribed in one patient, respectively [Table 3].

Utilization of various antihypertensive medications based on their DDD/patient was most frequent for amlodipine (91.41), followed by telmisartan (41.07). Among the medicines that account for 90% of DDD of prescriptions, i.e., DU90%, five drugs were within DU90%. Amlodipine was most used accounting for 47.49% of total DDD prescribed, followed by telmisartan at 21.33%, furosemide at 8.75%, hydrochlorothiazide at 7.11%, and enalapril at 6.5% [Table 4].

In our study out of total patients, 21 patients reported ADR in the 2^nd week and 17 patients reported ADR in the 8^th week of follow-up. The severity assessment of ADR was performed by the Hartwig and Siegel scale.⁹ No lethal and severe ADR were reported. On the 2^nd week of follow-up, 6(28.57%) ADRs reported were of moderate category and 15(71.42%) were of mild category, while on the 8^th week of follow-up, 5(29.41%) ADRs were in the moderate category and 12(70.58%) were in the mild category [Table 5].

DISCUSSION

Antihypertensive drug therapies have evolved in the last decades due to an increasing understanding of pathophysiology of hypertension. Multiple classes of antihypertensive drugs are available for treatment of hypertension, which creates confusion among prescribers to choose the most appropriate drug for a particular patient. Drug utilization review or medication utilization evaluation studies are one of the potential tools that help to study drug utilization patterns among prescribers, patients, and the healthcare facility. In addition, these studies also help to provide feedback to prescribers regarding their performance and prescribing behavior. Thus, this research had been undertaken with the aim of observing and analyzing the prescription patterns of antihypertensive medications within the outpatient department of a tertiary care hospital.

Most of the patients in our study were between the 61 and 75 age range (41.33%), with those over 75 (30.0%) making up the second largest group. This aligns with studies by Naik HG et al.¹⁰ (2019), Hussain SS et al. (2017), and Singh D et al. (2020), wherein most patients fell within the same age demographic.^10-12 In present study, 77(51.33%) patients were males, whereas 73(48.67%) were females, which is comparable to the research carried out by Naik HG et al. (2019), where the percentage of males and females was 50.33% and 49.46%, respectively.¹⁰ A higher number of prescribed medications per encounter can cause an increased likelihood of side effects, higher risk of drug interactions, decrease in drug effectiveness, more risk of allergic reactions, and potential confusion for the patient in managing multiple medications. In current study, an average of 5.85 drugs and 2.30 antihypertensive drugs, respectively were prescribed per prescription. These values are less than those of a study conducted in Tamil Nadu by Nachiya JRA et al. (2015) (7.56 ± 2.76).¹³ It is encouraging to know that in current study average number of drugs prescribed in patients was less as reported in previous study.

The use of brand names in prescriptions may be attributed to the vigorous advertising strategies employed by pharmaceutical corporations and thus accounts for the majority of irrational prescribing. Use of generic names for prescribing of medications offers cost-effectiveness, clarity, increased accessibility, regulatory compliance and reliability, collectively ensuring affordable, standardized, and accessible healthcare. This is particularly relevant for a nation like India, which encounters financial constraints due to the poor socioeconomic status of the majority of its patients. Therefore, it is essential to educate healthcare providers to encourage the prescription of generic drugs. In our analysis, 90.98% of the total drugs had been prescribed by using their generic nomenclature. This observation parallels a study conducted by Varakantham V et al. (2017), which found that 80.7% of the drugs were prescribed using their generic names.¹⁴ Singh D et al¹². (2020) stated that 38% of drugs were administered using generic names in their study; however, Gupta CN et al.¹⁵ (2019) discovered that only six percent of medications were prescribed with generic names in their research.^12,15

92% of the total drugs prescribed in present study were from the essential drugs list (EDL). The drugs prescribed from EDL are much better in our study as compared to another study, in which only 65% of drugs were prescribed from the EDL.¹⁶ While our study highlighted a substantial use of drugs listed in the EDL, it brought to light a significant prospect for refining prescribing practices. This observation indicates that there is opportunity to further optimize the process of drug prescription in accordance with the principles of rational drug use.

Of the total prescribed medications, 89.38% were dispensed by the hospital pharmacy. The patient had a 72% understanding of the appropriate pharmaceutical dosage, surpassing the findings of Nachiya JRA et al., (2015) where only 38.3% of patients possessed accurate knowledge of drug dosage.¹³ This practice can be enhanced by increasing awareness about importance of effective communication among pharmacist. This includes ensuring they effectively communicate essential details such as the accurate dosage, duration, and frequency of drug administration to patients.

Out of total 876 drugs prescribed, 343(39.15%) drugs belonged to a class of antihypertensive drugs. CCBs were the first choice given for hypertension in 107 (31.19%) participants, while ARBs were used as antihypertensive in 61 (17.78%) participants. A comparable outcome was observed in a study done by Suthar KM et al. (2022), Singh D et al. (2020), Naik HG et al. (2019), Varakantham et al. (2017), Datta S et al. (2016), and Rajasekhar DG et al. (2016) where CCBs were most frequently prescribed antihypertensive drugs.^{9,12,14,16-18} Drugs like renin-angiotensin inhibitors and CCBs effectively and safely lower blood pressure levels, with good tolerability. CCBs are commonly used due to their efficiency and wealth of information on minimizing cardiovascular and renal effects of hypertension, in both monotherapy and combination therapy.

Among CCBs, amlodipine was prescribed in 107(71.33%) patients. The second most common group of antihypertensives prescribed was ARBs in 61(40.67%) patients, and telmisartan was the most commonly prescribed drug among ARBs. Similar to our study outcomes of previous research demonstrated that amlodipine was the most commonly prescribed antihypertensive drug, followed by telmisartan.¹² In contrast to our study, results of studies by Suthar KM et al. (2022) and Naik HG et al. (2019) demonstrated that amlodipine was the most commonly prescribed drug, followed by diuretics, i.e., hydrochlorothiazide and furosemide, respectively.^10,17 Another study reported that amlodipine was most frequently prescribed, followed by atenolol.¹⁶ Study by Narkar NS et al. (2021) showed that the ARBs were most commonly prescribed antihypertensive medications, followed by CCBs and diuretics.¹⁹

In the present study, prescribed antihypertensive drugs were categorized according to the ATC classification and the DDD system. Results revealed that the average dose of prescribed drugs per day was 8.98 mg for amlodipine and 47.61 mg for telmisartan. In a previous study done by Singh et al. (2020), the average daily dose prescribed was 5mg for amlodipine and 46.15 mg for telmisartan.¹² Utilization of various antihypertensive medications based on their DDD/patient was most frequent for amlodipine (91.41) in this study, followed by telmisartan (41.07). Among the medicines that account for 90% of DDD prescriptions, i.e., DU90%, were amlodipine, telmisartan, furosemide, hydrochlorothiazide, and enalapril. Similar to our study antihypertensive drug consumption in DDD/1000 patients/day was highest for amlodipine 4.724, followed by telmisartan 4.723 as reported by Singh D et al. (2020), while in another study antihypertensive drug consumption in DDD/1000 patients/day was highest for amlodipine (17.50), followed by furosemide oral (6.81) and furosemide i.v. (3.74).^10,12 Amlodipine has a long half-life and can be given as a single daily dose. Also, blood pressure takes one week to return to baseline if amlodipine is discontinued, and provides better safety as no severe rebound hypertension is seen with amlodipine.^20,21 In the present study, at the 2^nd and 8^th week of follow-up, no severe ADRs were reported with antihypertensive medications. Nevertheless, a previous study done by Chandra S et al. (2019) noted 37 ADRs, and on the Hartwig and Siegel scale, 1(2.7%) ADR was in the severe category, while 14(37.8%) and 22(59.4%) were in the moderate and mild categories.²²

CONCLUSION

This study provides insights into demographic characteristics, prescribing indicators, patient care indicators, facility metrics, current prescribing patterns of antihypertensive medications, and associated ADRs. The drug utilization patterns observed in this study were quite similar to those found in other studies conducted across India. DUS can be a valuable tool for understanding patterns in hypertension treatment and optimizing clinical practice to improve patient outcomes. By routinely evaluating prescribing patterns, healthcare practitioners may ensure that patients obtain the most suitable and efficacious medicines for hypertension.