Evaluation of drug utilization in cardiovascular disease at a teaching and referral hospital in Northern Telangana.

OBJECTIVES: Cardiovascular disease (CVD) is the primary cause of death globally despite the advanced health-care facilities. Extensive disparity exists in pharmacotherapy pattern among CVD patients where rational drug use plays a pivotal role in promoting safety and efficacy. The study focused to evaluate drug utilization using the World Health Organization (WHO) prescribing indicators and defined daily dose (DDD) in patients admitted to a teaching/referral hospital in Northern Telangana.
MATERIALS AND METHODS: A total of 1120 medical records were analyzed for drug utilization for a period of 7 months. Prescription pattern was assessed using the WHO prescribing indicators and DDD to measure individual drug utilization categorized under anatomical-therapeutic-chemical classification.
RESULTS: Of the total admissions, 58.57% (55.19 ± 15.19 years) were male and 41.43% (56.64 ± 15.28 years) were female where coronary artery disease was the most common cause of admission followed by cardiomyopathy. Among prescribing indicators, percentage of drugs with generic names was least accounted with 26.86% and 18.95% during hospitalization and discharge, respectively. A mean of 11.55 (hospitalization) and 6.55 (discharge) drugs were prescribed per prescription. Antiplatelet (72.86%) and statin (80.62%) use was predominate during complete therapy. The DDD of furosemide (109.33) was found to be high, followed by atorvastatin (64.6), enalapril (58.44), aspirin (58.14) and clopidogrel (53.2).
CONCLUSION: Polypharmacy and least use of generic name were observed in the study which may affect the rationality. The use of antiplatelets, statins, and angiotensin-converting enzyme-inhibitors was appropriate, but furosemide overuse is of major concern. Therefore, appropriate prescription writing improvises treatment compliance in the patients, which results in rationality. Copyright:

Introduction

Cardiovascular disease (CVD) is the major reason of mortality among noncommunicable diseases (NCDs), constituting 26% in India.[12] Relative to other NCDs, deprived quality of life and high mortality rate is mounting with CVDs regardless of highly developed health-care facilities. In India, patients with acute coronary syndrome (ACS) have higher rate of ST-elevation myocardial infarction (STEMI) than do patients in developed countries; the treatment options differ between rich and poor which significantly altered mortality and morbidity.[3] Women develop CVD at older age and have greater comorbidities than men, though treatment and outcome did not differ after adjusting potential confounders.[4] Appropriate and safe drug use is a key factor in achieving quality health and accurate health care for hospitalized as well as ambulatory patients. Extensive disparity exists in the pharmacotherapy pattern among CVD patients where rational drug use plays a pivotal role in promoting safety and efficacy. Polypharmacy is warranted in CVDs as it results in irrationality; hence, prescribing indicators were developed to assess the prescribing performance in primary care by the International Network for Rational Use of Drugs and World Health Organization (WHO).[5]

Drug utilization research facilitates identification of clinical drug utilization and its impact on health-care system.[6] Defined daily dose (DDD) is one such measurement which identifies the clinical drug use and it is defined as “the assumed average maintenance dose per day for a drug used for its main indication in adults.”[6] It is a unit of measurement and does not essentially correspond to the prescribed or recommended daily dose. Drug utilization studies in India demonstrate the occurrence of wide spectrum of various cardiovascular drugs utilized for prophylaxis and therapeutic indication.[789101112] Continuous audit in critical care would provide insights into current practice and feedback for rationalizing prescribed practices.[13] Hence, we proposed to study the drug utilization pattern by assessing the prescribing performance of teaching/referral hospital in Warangal, Telangana, India, using the WHO prescribing indicators and metric calculation DDD.

Materials and Methods

Study design and patients

A prospective observational study was conducted in a teaching/referral hospital in Warangal, Telangana, India, for a period of 7 months (January–July 2016), which included a total of 1120 patients admitted to intensive coronary care unit. The present study is a part of PhD thesis, where necessary permission from the hospital (No.: 350/UCPSc/KU/2015, Dated 10/12/2015) and ethics approval from Kakatiya Institutional Ethics Committee (KIEC) (Approval No.: KIEC/KMC/MGMH/NCT/2016/12/001b) were obtained for conduct of the study.

Methods

All the medical prescriptions were collected and the data was used to analyze the prescription pattern by prescribing indicators[13] and individual drug use by DDD measure. The WHO indicators intended to be used in primary care center/ambulatory patients, but in this study, it was extended to assess prescription pattern during hospitalization too. The prescribing indicators are (a) average number of drugs per prescription, (b) percentage of the drugs prescribed by their generic names, (c) percentage of the prescriptions with antibiotics prescribed, (d) percentage of the prescriptions with injections prescribed, and (e) percentage of the drugs prescribed from the essential drug list (EDL) or the hospital formulary.[14]

The quantification of the individual drug was done using DDD. This concept was developed to surmount the objection besides the traditional measurement units of drug utilization. It is expressed as DDD (for each drug in individual patient); DDD/100 bed-days (for inpatients in a hospital); and DDD/1000 persons-years (for inhabitants in a region/country). In the present study, DDD was expressed as DDD/100 bed-days since inpatients' drug use was considered and calculated using the equation below:[6]

Statistical analysis

The data was collected, compiled in MS-Excel, and analyzed for counts and percentages. The mean and standard deviation was computed for continuous variables. Graphical representation has been used for visual interpretation of the analyzed data.

Results

Sociodemographic characteristics

Of the total 1120 records, males were 58.57% (55.19 ± 15.19 years) and females were 41.43% (56.64 ± 15.28 years). Majority of males were admitted between 61 and 70 years and females between 51 and 60 years of age. Surprisingly, the prevalence rate was high in males and mortality rate was high in females (9.7%). When screening inpatient prescriptions, it was found that 78.39% were discharged, 8.84% left against medical advice, 8.21% deaths, and 4.55% could not be tracked. Urbanization is predominant (57.05%) underlying determinant compared to rural life (42.95%) of the study population. The mean length of hospital stay was 5.889 ± 3.599 days. Deaths due to ischemic heart disease (IHD) would be the cause for developing arrhythmias and heart failure (HF). Coronary artery disease (55.27%) and cardiomyopathy (24.02%) were the common diagnoses, followed by hypertension and HF as depicted in Figure 1.

Figure 1

Prevalence of cardiovascular and noncardiovascular diseases in the study population in percentage

Drug utilization

A total of 12,941 drugs were prescribed during hospitalization and 5745 drugs at discharge. During hospitalization, 56.5% patients were given 7–12 drugs, 32.14% were given 13–18 drugs, and at discharge 50.63% were prescribed with 7–9 drugs. Number of drugs per prescription is depicted in Figure 2.

Figure 2

Number of drugs received per prescription in the study population

Drug utilization during hospitalization

The DDD of different cardiovascular drugs is summarized in Table 1; it was found that furosemide (109.33), atorvastatin (64.60), enalapril (58.43), aspirin (58.14), and clopidogrel (53.219) were highly used. Among various cardiovascular drugs, majority of prescriptions included antiplatelets, lipid-lowering agents, angiotensin-converting enzyme (ACE) inhibitors, diuretics, antianginals, anticoagulants, and beta blockers, as shown in Table 2.

Table 1

Defined daily dose of cardiovascular drugs in the study population

ATC code	Drug name	DDD/unit	ROA	Cases	DDD/100 bed-days
A02BC02	Pantoprazole	40 mg	O, P	903	63.91
A10BA02	Metformin	2 g	O	255	2.27
C01AA05	Digoxin	0.25 mg	O, P	225	16.136
C01BD01	Amiodarone	0.2 g	O, P	42	6.023
C01CA03	Norepinephrine	6 mg	P	46	0.182
C01CA07	Dopamine	0.5 g	P	64	0.303
C01CA08	Dobutamine	0.5 g	P	56	0.332
C01DA08	Isosorbide dinitrate	20 mg	SL	515	38.472
C01DA14	Isosorbide mononitrate	40 mg	O	59	2.193
C01DA16	Nicorandil	40 mg	O	162	3.577
C01DA17	Ivabradine	10 mg	O	11	0.771
C03BA08	Metolazone	5 mg	O	169	27.742
C03CA01	Furosemide	40 mg	O, P	715	109.33
C03CA04	Torsemide	15 mg	O, P	18	1.03
C03DA01	Spironolactone	75 mg	O	136	6.489
C07AA05	Propranolol	0.16 g	O	1	0.025
C07AB02	Metaprolol	0.15 g	O, P	467	11.737
C07AB03	Atenolol	75 mg	O, P	3	0.189
C07AG01	Labetalol	0.6 g	O	8	0.006
C07AG02	Carvedilol	37.5 mg	O	223	3.013
C08CA01	Amlodipine	5 mg	P	69	5.371
C08CA05	Nifedipine	30 mg	O, P	2	0.071
C08DA01	Verapamil	0.24 g	O, P	50	1.134
C08DB01	Diltiazem	0.24 g	O	3	0.062
C09AA02	Enalapril	10 mg	O, P	792	58.436
C09AA05	Ramipril	2.5 mg	O	4	0.284
C09CA07	Telmisartan	40 mg	O	12	4.676
C10AA05	Atorvastatin	20 mg	O	903	64.601
B01AA03	Warfarin	7.5 mg	O, P	2	0.0411
B01AA07	Acenocoumarol	5 mg	O	38	1.2804
B01AB01	Heparin	10 TU	P	67	0.0397
B01AB05	Enoxaparin	2 TU	P	615	0.2187
B01AC04	Clopidogrel	75 mg	O	738	53.196
B01AC06	Acetylsalicylic acid	1 tab	O	816	58.14
B01AD01	Streptokinase	1.5 MU	P	123	1.458
B01AD11	Tenecteplase	40 mg	P	10	0.089
R03AC02	Salbutamol	0.8 mg	Inhalation	155	6.18
J01DD04	Ceftriaxone	2 g	P	255	21.33

ATC=Anatomical-therapeutic-chemical, DDD=Defined daily dose, O=Oral, P=Parenteral, RoA=Route of administration, SL=Sublingual

Table 2

Overall drug utilization in total number of prescriptions of the study population

Drugs prescribed	In-hospital (n=1120)	At discharge (n=877)
Cardiac drugs
Antiplatelets	964 (86.07)	716 (81.64)
Anticoagulants	623 (55.62)	24 (27.37)
Thrombolytics	133 (11.87)	0
Antianginals	638 (56.96)	347 (39.58)
Statins	903 (80.62)	672 (76.62)
ACE inhibitors	795 (70.98)	568 (64.77)
Angiotensin receptor blocker	12 (1.07)	11 (1.25)
Beta blockers	471 (42.05)	566 (64.54)
Alpha and beta blockers	225 (20.09)	192 (21.89)
Diuretics	738 (65.89)	483 (55.07)
Antiarrhythmics	47 (4.2)	13 (1.48)
Calcium channel blockers	121 (10.8)	71 (8.1)
Inotropes	356 (31.79)	134 (15.28)
Noncardiac drugs
Oxygen	467 (41.7)	0
Bronchodilators	226 (20.18)	47 (5.36)
Intravenous fluids	381 (34.02)	0
Antidiabetics	180 (16.07)	144 (16.42)
Antibiotics	433 (38.66)	139 (15.85)
Centrally acting drugs	183 (16.34)	43 (4.9)
Antiulcer drugs	938 (83.75)	616 (70.24)
Antihistamines	171 (15.27)	5 (0.57)
Laxatives	127 (11.34)	11 (1.25)
Mucokinetics	134 (11.96)	23 (2.62)
Antiemetics	110 (9.82)	12 (1.37)
Antidiarrheals	38 (3.39)	4 (0.46)
Analgesic, anti-inflammatory, and muscle relaxant	86 (7.68)	84 (9.58)
Thyroid drugs	11 (0.09)	12 (1.37)
Vitamin supplements	298 (26.61)	388 (44.24)
Overall electrolyte	394 (35.18)	131 (14.94)
Erectile dysfunction drugs	48 (4.29)	37 (4.22)
Antivertigo	15 (1.34)	5 (0.57)
Ursodeoxycholic acid	11 (0.09)	5 (0.57)
Benign prostatic hyperplasia drug	1 (0.01)	1 (0.1)

ACE=Angiotensin-converting enzyme

Antiplatelets

Aspirin was the major antiplatelet prescribed in 72.86%, followed by clopidogrel in 65.89% of prescriptions. Only 21.7% of prescriptions have fixed combination of these two medications. In ACS, only 80.67% were prescribed with aspirin and 77.45% with clopidogrel.

Anticoagulants

Enoxaparin, low-molecular-weight heparin (LMWH) utilization, was predominated in 53.66% of prescriptions compared to 4.73% with unfractionated heparin. Based on the physician recommendations, both are sequentially prescribed in 1.25% of prescriptions. Among oral anticoagulants, acenocoumarol (acitrom) was prescribed in 3.39%, followed by warfarin in 0.18% of prescriptions. Males have received more LMWH (58.03%) and unfractionated heparin (62.26%) than females.

Thrombolytics

Streptokinase (10.98%) was mostly prescribed whereas tenecteplase (0.89%) was found in few cases as it was newly introduced in the hospital drug formulary due to its beneficial effects and ease of administration compared to streptokinase. Only about 16.7% were prescribed with streptokinase in ACS patients.

Lipid-lowering agents

Atorvastatin was commonly prescribed in 80.62% of prescriptions.

Inotropic agents

Digoxin was mostly prescribed (20.09%) and others were least prescribed (atropine, 6.96%; dopamine, 5.71%; dobutamine, 5%; adrenaline, 4.82%; and noradrenaline, 4.10%). About 35.9% of HF patients were prescribed with digoxin.

Antiarrhythmics

Amiodarone was found in 3.75% of prescriptions, followed by adenosine and isoprenaline (0.71% and 0.09%, respectively).

Antihypertensive agents

Among ACE inhibitors, enalapril was prescribed in 70.08%, followed by ramipril in 0.27% of prescriptions. Angiotensin receptor blockers (ARBs) were prescribed least, i.e., telmisartan in 0.89% and combination drug (telmisartan + hydrochlorothiazide) in 0.18% of prescriptions. Among diuretics, majority of prescriptions have furosemide (63.84%) than torasemide (1.61%), metolazone (15.09%), spironolactone (12.14%), and diuretic combination (4.02%). The use of diuretic was about 87.56% in HF. Beta blockers such as metaprolol, atenolol, and propranolol were prescribed in 43.57%, 0.27%, and 0.09% of prescriptions, respectively. Only 42.56% in ACS and 38.34% in HF were given beta blockers. Alpha and beta blockers such as carvedilol and labetalol were prescribed in 19.91% and 0.27% of prescriptions, respectively. Among calcium channel blockers (CCBs), amlodipine (6.16%) was mainly prescribed compared to diltiazem (0.27%) and verapamil (4.46%). Centrally acting antihypertensive methyldopa was prescribed in 0.09% of prescriptions.

Antianginal agents

Isosorbide dinitrate was mostly prescribed in 45.98% of prescriptions and other antianginals include nicorandil (14.46%), oral glyceryl trinitrate (9.82%), injectable glyceryl trinitrate (9.46%), isosorbide mononitrate (5.27%), ivabradine (0.98%), and ranolazine (0.27%). In ACS, only 11.63% were prescribed with nitrates.

Others

Among noncardiac drugs, pantoprazole (80.44%) was prescribed mostly, followed by intravenous fluid normal saline, 31.7%; ceftriaxone, 22.77%; multivitamin, 18.75%; tramadol, 13.75%; alprazolam, 12.77%; and Phenergan, 12.77%. An overview of noncardiac drugs is provided in Table 2.

Prescription pattern during discharge

The average drugs per prescription during hospitalization was 11.55 (range of 2–32) and during discharge was 6.55 (range of 2–10) with least number of drugs with generic names shown in Table 3. During discharge, majority were prescribed with antiplatelets, 81.64%; statins, 76.62%; ACE inhibitors, 64.77%; beta blockers, 64.54%; diuretics, 55.07%; and antianginals, 39.58%, followed by anticoagulants, nonselective beta blockers, cardiotonic, CCBs, and ARBs, and the details are summarized in Table 2. All the prescribed drugs are present in EDL and meet the standard treatment guidelines. Females received less aspirin (42.56%), statins (39.58%), and ACE inhibitors (41.7%) than males.

Table 3

Pattern of prescription writing using the World Health Organization prescribing indicators in the study population

Prescribing Indicators (optimal level)	In-hospital (n=1120), %	At discharge (n=877), %
Average number of drugs prescribed per prescription (≤3)	11.55	6.55
Percentage of drugs prescribed by generic name (100%)	26.86	18.95
Percentage of prescriptions with an antibiotic prescribed (≤30%)	38.66	15.85
Percentage of prescriptions with an injection prescribed (≤10%)	99.55	6.27
Percentage of drugs prescribed from the national EDL (100%)	97.01	94.74

EDL=Essential drug list

Prescription errors

Negligible prescription errors were found in the discharge medication, in which the type of error was repetition of drug and more drugs of the same class which may lead to increase in dose and possibly development of serious side effects.

Discussion

Gender distribution was nearly equal, and majority were younger (<45 years) similar to CREATE registry[3] than those in observational studies of developed countries (63–69 years).[1516] Coronary artery disease and cardiomyopathy were the common causes of hospitalization. It was reported that the rate of STEMI and NSTEMI is equal in patients with IHD unlike CREATE study.[3] In contrast to DEMAT study,[4] both the genders of the present study are equal in the ACS prevalence despite the occurrence of potential confounders. Compared to national data on cardiovascular mortality rate (26%),[2] the present findings inhospital mortality was 8.21% within the margin where most deaths due to ACS are documented, which would be the cause for developing arrhythmias and HF.

Antiplatelets, statins, ACE inhibitors, and diuretics were mostly prescribed, which certainly improve the treatment outcomes. Almost all patients received antiplatelets similar to other centers in Southern India.[1718] Enoxaparin was found effective in treating pulmonary embolism, venous thrombosis, and unstable angina,[19] and the utilization of anticoagulants was optimal to other Indian studies (75%–85%).[320] Recent addition of tenecteplase in the hospital drug formulary was identified in the study which was proved more advantageous than streptokinase. The use of streptokinase was less where only about 10.98% were thrombolyzed within the window period for myocardial damage. Atorvastatin was the only lipid-lowering drug utilized, but it was found that the dose was not calculated according to low-density lipoprotein cholesterol levels and was lower than the recommended use. The use of ACE inhibitors and statins was optimal and similar to other studies.[318] Inotrope use is short term to stabilize the hemodynamic status as long-term use escalates mortality. Similar to ACS-US registry,[21] females receive less heparin and ACE inhibitors, aspirin, and statins than males.

The DDD concept provides a rough estimate on the number of units of drug used per 100 beds in a day. It was assumed that every patient prescribed with a definite drug takes specific DDD [Table 1] every day, disregard to the dosage alteration and the patient-related factors. It was observed that DDD of furosemide was markedly high in comparison with others; therefore, it has to be utilized with precaution as it results in nutrient deficiencies with fluid loss.

The use of aspirin, clopidogrel, beta blockers, and ACE inhibitors in ACS was low, compared to East[7] and South India[89] and high in some regions of South India.[10] In HF, the use of diuretics and beta blockers was almost equal,[11] whereas the use of digoxin and ACE inhibitors was high compared to South India.[1112]

Polypharmacy was high for discharged patients and it may be acceptable as the study center is a tertiary care setting where majority of patients are hospitalized with several comorbidities. A relationship between polypharmacy and comorbidities is a proven risk factor for adverse reactions, which significantly augment the duration of hospitalization.[22] It is strongly recommended that the use of generic name in prescriptions enable improved information exchange and better communication between health-care providers.[23] A very low percentage of drugs, prescribed by generic name, was found, which is a major concern. Appropriate use of antibiotics and injectables was found in the study. As the inpatients receive more injections, probability to promote risk of blood-borne diseases is also high. However, the overuse/misuse of antibiotics is a global threat[24] and the use of injectables depends on the patients' condition, regardless of the availability of oral dosages during hospital stay. All the drugs used were from the EDL, which is imperative to promote rational drug use and cost effectiveness.[25] Prescription errors can be reduced using generic names, and polytherapy could be reduced using fixed combinations rather than single formulation which may potentially improve drug utilization.

Conclusion

The study concludes that during the study period, males were mostly admitted and the mortality rate was high in females. Irrational drug uses such as polypharmacy and nongeneric names were observed in the prescriptions. Cardiovascular drug doses are appropriate as the study center is a government one and here major concern relies on whether the drug was prescribed to the patient or not. Hence, rational drug use relies on accurate prescription writing, patient education, and compliance to the treatment which is vital in achieving the appropriate beneficial outcome.

Financial support and sponsorship

The research was supported by the UGC, New Delhi (RGNF-2016-17-SC-TEL-5373).

Conflicts of interest

There are no conflicts of interest.