Drug Use Evaluation of Antihypertensive Drugs Prescribed for In-patients at Tertiary Care Teaching Hospital

INTRODUCTION

Hypertension or high blood pressure is defined as having persistent, elevated systolic blood pressure of 140 mm Hg or above and/or diastolic blood pressure of 90 mmHg or above. Untreated or sub optimally treated hypertension could lead to increased risk of morbidity and mortality due to cardiovascular, cerebrovascular, or renal diseases.¹ Increase in age, male gender, increase in BMI levels, tobacco and alcohol were found to be significant independent predictors of hypertension. The prevalence dramatically increases in patients older than 60yrs; in many countries, 50% of individuals in this age group have hypertension.² Complications of hypertension account for 9.4 million deaths worldwide every year.³ Hypertension is responsible for 45% of deaths due to heart disease and 51% of deaths due to stroke. It is estimated that the worldwide prevalence of hypertension would increase from 26.4% in 2000 to 29.2% in 2025.⁴ The main benefit of any antihypertensive treatment is lowering of blood pressure and this is largely independent of the class of medicine used. Once the decision has been made to initiate antihypertensive treatment, choice of medicine should be based on individual patient characteristics including age and comorbidities. Diuretic monotherapy is the current recommendation of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure for initial antihypertensive therapy.⁵

Most hypertensive patients require more than one drug for optimum BP control. Expert panels recommend use of combination therapy with two or more medications for Stage 2 and higher hypertension and in high-risk patients. However, the use of multiple drugs reduces patient compliance. Fixed-dose combination therapy helps improve patient compliance and thus achieves the target BP.⁶

The use of drugs in hypertensive patients must be rational; this implies that the appropriate drugs must be prescribed in the right dose, at correct time interval and for a sufficient duration of time.⁷ This study therefore envisages evaluation of the pattern, extent, rationality and frequency of use of the antihypertensive drugs in the treatment of essential hypertension for information to the esteemed medical fraternity.

In the case of most diseases drug therapy will enhance health related quality of life. However, inappropriate use of drugs may be harmful and could evoke new adverse symptoms. Drug related problems are of major concern in view of their physical, psychological and economic burden to the patients and to society as a whole.⁸ Thus optimizing drug therapy by preventing drug – related problems may influence the health costs, potentially save lives and enhance patient’s quality of life.⁹ Drug therapy optimization by preventing drug related problems definitely has greater influence on health expenses, potentially save lives and improves patient’s quality of life.¹⁰

Polypharmacy is now common, and carries a high risk of drugdrug interactions and drug-disease interactions. These may cause adverse effects, or the therapeutic effects of the combined medicines may change, with serious consequences for health.¹¹

Drug utilization researches on antihypertensive are useful for evaluating physician prescribing practices, choice of individual drug, estimating use of other agents that are used to treat hypertension and way of improving prescribing.¹² Several studies have shown that there is possible reduction in DRP’s through pharmacist initiated changes in drug therapy. With this above background the authors are fascinated carry out this study with general objective, to study the drug utilization evaluation and analysis of drug related problems of antihypertensive drugs at tertiary care teaching hospital. The specific objectives were to study the prescribing pattern and the rationality of antihypertensive drugs and to find out the potential drug related problems among hypertensive patients.

MATERIAL AND METHODS

This is a prospective study carried at the Department of Medicine of the SN Medical College and HSK Hospital, Bagalkot, over a period of 6 months. It is an 820 bedded multispecialty tertiary care teaching hospital with different specialties and super specialities. HSK Hospital provides primary and specialized health care facilities to people in and around Bagalkot district. The study was approved by Institutional Human Ethics Committee [File No: SNMC/IECHSR/2014-15/A04g-1.1], S.N.M.C and H.S.K Hospital and research Centre, Bagalkot, India. The study was conducted in accordance with the ethical principles of the ethical committee guidelines.

Study population:

Inpatients of either gender aged ≥18 years with primary and secondary hypertension and Patients receiving antihypertensive drugs were outlined as the main criteria for the inclusion of the patient prescription to the study sample. Patients attending outpatient department and patients with gestational hypertension were excluded from the study. Upon applying the inclusion and exclusion criteria, a sample of n = 160 patient charts was considered for the analysis.

Study measures:

All inpatient of general medicine wards were reviewed on daily basis. The medication details of all these patients were collected and documented in a data collection form. The data collected from patients during the study includes

• The patient’s socio demographic data such as age, sex, weight etc.

• Disease specific information like past medical history, reason for admission, allergies.

• Medication history including drug administered, route of administration, dosage, drugs involved in type of drug related problems, reason for intervention, suggestion made by student pharmacist

• Acceptance and significances of pharmacist interventions were documented in a suitabledesigned patients data collection form.

The patient charts were assessed for obtaining the prescribing pattern, rationality, drug related problems using Micromedex, JNC 7 and IGH 3 guidelines. The efficacy of antihypertensive drugs was studied by statistical methods. Each drug related problem was categorized on the basis of Hepler and Strand¹³ as follows

• Untreated indication

• Drug use without indication

• Adverse drug reaction

• Drug interaction

• Sub therapeutic dosage

• Over dose

• Failure to receive drug

• Medical condition resulted from unindicated drugs

The drug related problems suggestions were categorized as

• Cessation of drug.

• Substitution of drug.

• Change in frequency of administration.

• Change in drug dose.

• Others.

The involvement of student pharmacist in therapeutic decision was rated by wood model, the levels were named as

Level 1: Annotative: The pharmacist is clarifying a prescription and/or the intervention of a prescriber. The prescriber makes no change.

Level 2: Corrective: The pharmacist is actively questioning a prescription to try to get it changed or corrected. Advice accepted or rejected. The prescription may or may not be changed.

Level 3: Consultative: The pharmacist is making an active contribution to a discussion. Advice before the decision of initiation of drug therapy. The prescription may or may not change.

Level 4: Pro-Active: The pharmacist suggest something, which has not been previous considered, advice may be accepted or rejected. The prescription may or may not change.

Statistical Analysis:

Data analysis was done using the statistical methods and continuous data was presented as mean±SEM, while categorical data was present as percentages. Differences between means of two groups were compared using student’s t test. A p-value less than 0.05 were considered as statistically significant.

RESULTS

Age group and gender wise categorization of hypertensive patients:

During the hospital stay of 160 cases we found, out of 95 male patients 17 (17.89%) belong to 70 and above age group followed by 32 (33.68%) under 60-69 years age group, 25(26.31%) under 50-59 years age group, 16 (16.84%) under 40-49 years age group, and 4 (4.21%) under 30-39 years age group, 1(1.05%) under 20-29 years age group. Out of 65 female patients 20 (30.76%) belong to 70 and above age group followed by 19 (29.23%) under 60-69 years age group, 13 (20%) under 50-59 years age group, 13 (20%) under 40-49 years age group. [Results were summarized in table 1].

Class of antihypertensive drugs prescribed for hypertensive patients:

Eight different classes of antihypertensive drugs prescribed for 160 inpatients were assessed during study. During this study period diuretics and Calcium Channel Blockers were equally and mostly prescribed 94(25.54%) for hypertensive patients followed by β blockers 55(14.94%), ACE inhibitors 48 (13.04%), Angiotensin receptor blockers 42 (11.41%), α + β blockers 14 (3.80%), centrally acting drugs 11 (2.98%), α blockers 10 (2.71%) [Results were summarized in table 2]. 

Pattern of drug regimen prescribed for hypertensive patients:

In our study, the table no: 3- 7 reveals that the two drug regimen were prescribed more in 87 (35.66%) hypertensive patients followed by mono drug regimen 69 (28.28%) and three drug regimen were 60 (24.59%) prescriptions, four drug regimen were 19(7.79%) and ≥ 5 drug combination were also seen in 9(3.69%) prescriptions.

Assessment of rationality of antihypertensive drug prescribed for patients:

The rationality of antihypertensive drugs in 160 prescriptions was assessed by JNC 7 and IGH guidelines. Out of 160 prescriptions 141(88.125%) prescriptions were rational and 19(11.875%) prescriptions were irrationally prescribed as per JNC 7, and 147(91.88%) prescriptions were rational and 13(8.13%) were irrationally prescribed as per IGH. Out of 141 rational prescriptions as per JNC 7 38 patients were admitted in ICCU and 103 patients were in Medical wards and out of 19 irrational prescriptions 8 patients were admitted in ICCU and 11 in Medical wards. As per IGH 147 prescriptions were rational out of which 43 patients were admitted in ICCU and 104 were admitted in Medical wards and 13 prescriptions were found as irrational of which 4 patients were in ICCU and 9 patients in Medical wards. [Results are summarized in table 8-9].

Study of efficacy of antihypertensive agents on hypertension patients:

During the hospital stay the various types of antihypertensive drugs were prescribed to patients to reduce SBP & DBP. Out of these Amlodipine significantly reduced SBP (p 0.0003); Ramipril reduced both SBP (p 0.0416) and DBP (p 0.0446) significantly. In combination therapy Amlodipine + Atenolol showed significant reduction in SBP (p 0.0129) and DBP (p 0.0047) on discharge day when compared with BP on admission and other combinations like Amlodipine + Furosemide showed reduced SBP (p 0.0122) significantly and Furosemide + Ramipril (p 0.0139) significantly as compared to SBP on admission and the three drug combination like Amlodipine + Telmisartan + Hydrochlorothiazide showed significant reduction in SBP(p=0.0069) & DBP(p=0.0203) accompanied with BP on admission and the remaining results were summarized in table 10-14.

Comparison of efficacy between mono and combination therapy:

We had chosen 2 drug and their 2 combinations to compare the efficacy of drugs. Table 6.1 reveals that mean reduction in SBP increased in patients prescribed Amlodipine and Atenolol combination when compared with mean reduction in SBP of only Amlodipine treated patients but is not significant. Mean reduction in SBP increased in Furosemide and Amlodipine received patients as compared with Furosemide alone treated and there is increase in mean reduction in DBP in patients treated with combination of Furosemide and Amlodipine as compared with Furosemide alone. [Results were summarized in table 15-16].

Assessment of Types and Description of various DRPs found in patients:

The various Drug related problems like improper drug selection, Adverse drug reactions, Overdose, Drug – drug interactions and prescriptions with wrong frequency were assessed in patient. There were 5(0.97%) improper antihypertensive drug selections found in prescriptions like Labetalol used in COPD, Clinidipine used in CCF and ACEI and ARBs given together and 5(0.97%) adverse drug reactions like Atenolol induced bradycardia, Amlodipine induced pedal edema, Ramipril induced dry cough. 9(1.73%) prescriptions contained significant interactions which include Ramipril – Spironolactone caused hyperkalemia, Insulin – Moxifloxacin caused hypoglycemia. One (0.19%) prescription contained overdose of Furosemide administration and there were 35(6.73%) wrong frequency drug prescriptions like Hydrochlorothiazide given at night, Telmisartan given twice daily [Results are summarized in table 17].

Assessment of drug interactions found in antihypertensive prescriptions:

During the study, a total of 520 drug related problems were found, out of which 474 were drug interactions. In this 149(31.43%) were found as Major drug interactions with 48 prescriptions containing Aspirin – Clopidogrel interactions, Moderate 320 (67.51), of which 37 prescriptions were of Atorvastatin – Clopidogrel interactions and 23 prescriptions had interactions of Aspirin – Ramipril, Minor 3(0.63) and contraindications were 2(0.42%).The contraindicated drugs were Carbidopa – Linezolid and Levodopa – linezolid because this combinations cause hypertensive crisis [Results were summarized in table 18].

Assessment of antihypertensive drugs affecting organ systems by various DRPs:

Out of 26 DRP’s 11(42.30%) drugs affected the renal system, 7(26.92%) drugs affected cardiovascular system and 4(15.38%) drugs affected both endocrine and respiratory systems [Results summarized in table 19].

Suggestions provided by the intervening student pharmacist:

During the hospital stay, 9 (34.62%) drug – drug interactions were suggested as significant like Aspirin+ Clopidogrel which was intervened to monitor PT and INR levels and intervention was made to monitor serum potassium levels of Ramipril+ Spironolactone. The frequencies of administration of 8 (30.77%) drugs were changed, for example Hydrochlorothiazide given at night was suggested to administer during morning. 5 (19.23%) drugs were suggested to substitute for the elimination of the DRP like Telmisartan was substituted for Ramipril induced dry cough. Suggestions were made in 2(9.69%) drugs like Labetalol and Carvedilol used in COPD for the cessation of the drug use due to its contraindications and 2(9.69%) drugs were suggested to change the drug dose like Furosemide given 80 mg thrice a day to twice a day [Results are summarized in table 20].

Assessment of the outcome of pharmacist interventions: The suggestions were evaluated by the physician and out of 26 interventions, 19(73.07%) were accepted and 7(26.92%) were not accepted change in drug therapy was done in 9(34.61%) and 17(65.38%) drug therapies remained unchanged [Results are summarized in table 21].

Pharmacist involvement in drug therapy decision making: The 26 DRPs were categorized as per the level of assessment from level 1 to level 2.The level 1 contained only 12 drugs (46.15%) followed by 14(53.85%) in level 2 [Results are summarized in table 22]

References consulted for retrieving proper evidence: For the references used for finding the total 520 DRPs were obtained from the 3 resources. Out of the 3 resources, secondary resource like Micromedex, was used in high proportion 479(92.11%), primary resources like JNC 7 and IGH guidelines were also referred 25 (4.80%).The tertiary resource also were used in 16 (3.08%) interventions [Results were summarized in table 23].

DISCUSSION

Drug utilization research may provide insights into different aspects of drug use and drug prescribing, such as pattern of use, quality of use, determinants of use, and outcome of drug use.¹⁴

A study conducted in Davengere also shows the prevalence of hypertension was 4.9% in 18-29 year age group, which increased to 31.2% in subjects of age over 70 years40. This is in occurrence with our study where maximum numbers of patients were found in age group 50-70 years. This represents that increasing in age is a risk factor to develop hypertension in India.

In our study most prescribed class of antihypertensive drugs were diuretics and CCBs followed by beta blockers. A similar study conducted in an out-patient department by Arshad H. Mohd et al, shows that the most commonly prescribed drug classes involved were calcium channel blockers followed by Angiotensin receptor II blockers.¹⁵

In our study, it was observed that the two drug regimen was prescribed more (35.66%) followed by mono drug regimen (28.28%) and three drug regimen (28.28%) respectively. A combination of agents from different drug classes is 2 to 5 times more effective in lowering BP than increasing the dose of monotherapy. A low dose of two agents reduces adverse events too, not only those that are dose related but also because the mechanism of action of one drug may interfere with the pathways for adverse effects of the second drug.² Three drug single – pill fixed dose combinations expand the options for effectively treating hypertensive patients with stage II hypertension who have not attained goal BP with two drugs.¹⁶ For comparison 73% of hypertension patients prescribed antihypertensive combination in survey conducted in Nigeria.¹⁷ In an Indian study 60% and 40% of patients reviewed combination and monotherapy respectively.¹⁸

In our study rationality was assessed by using Joint National Committee – VII and Indian Guidelines of hypertension. These guidelines were intended to provide practitioners with a standard approach to the rational, safe, and effective use of antihypertensive for prevention of hypertension based on currently available clinical evidence and emerging issues. Rational recommendations of antihypertensive were very high for the hypertensive patients in our study that is 141(88.125%) rationally as per JNC 7 and 147 (19.88%) as per IGH. The remaining 19(11.875%) prescriptions were irrationally prescribed as per JNC 7 and 13(8.13%) prescriptions as per IGH.

A recent study conducted in postmenopausal women by Vishal.R. Tandon et al shows antihy pertensive prescription trends largely adhere to existing guidelines and are rational except polypharmacy, generic and fixed dose combinations prescribing, were some of the common pharmacologically considered irrationality noticed.¹⁹ Similarly, in our study Physicians were well adhered to both JNC 7 and IGH guidelines which was a positive signal to control hypertension for patients visiting our hospital.

While studying efficacy of mono and combination therapy in our study, it was observed that combination therapy showed significant raise in mean reduction of SBP and DBP. This once again proves the efficacy of combination therapy over monotherapy.

As we discussed above, in our study combinations also used more than 50% thus there were more possibility of DDI’s in our prescriptions and also various studies have shown that potential drug – drug interactions are frequent when patients receive multiple prescriptions.²⁰

A study conducted on the assessment of drug therapy problems in Adama hospital Medical College, East Ethiopia was compared with our study and revealed that the most drug related problems of antihypertensive drugs were drug interactions followed by adverse drug reactions majorly dry cough followed by peripheral edema and decreased heart rate. The other drug related problems include prescriptions containing wrong frequency and overdoses. These drug related problems caused non- medication adherence of patients that led to a poor effectiveness of therapy. The data collected on the burden of drug related problem among hypertensive patients was helpful for policy makers to effectively plan in preventing risks caused by these problems.²¹

In present study we found 474 DDI’s in prescriptions of 160 hypertension patients in our tertiary care hospital. Out of these, 9(1.73%) interactions were clinically significant. A similar study carried out in a superspeciality hospital setting in South India shows that among the 227 patients, 48 of them developed 53 clinically significant interactions.²²

These potential DDI’s can be reduced in presence of clinical pharmacists and understand about DDI by physicians which was already proved in study conducted in Thailand.²³ Antihypertensive drugs affecting organ systems by various drug related problems were assessed to improve the understanding of the pharmacology of these drugs. For example, diuretics affect the renal system and any DRPs to these classes of drugs affect this system and decrease the effect of drug. Therefore this assessment plays an important role in improving the effectiveness of drugs.

Suggestions were provided by the intervening student pharmacist on the significant drug – drug interactions, adverse drug reactions, wrong frequencies and contraindications to equally involve with the physicians to improve the patient understanding and care. A preliminary interest of pharmacist was to analyze, identify, categorize, minimize and prevent the DRPs.

Pharmacist interventions were evaluated by the physicians to develop an effective prescription pattern. Pharmacist intervention suggestion in the present study was found to be effective, most of the interventions were accepted (73.07%) including change in drug therapy, change in dose of drug and change in frequency of prescribed drugs. But few suggestions (26.92%) in prescriptions were not accepted.

CONCLUSION

Our study on antihypertensive drugs at tertiary care teaching hospital shows that the choice of drugs reasonably complies with the JNC 7 and IGH guidelines on management of hypertension. Overall the pharmaceutical care is placed as an important strategy for the resolution of a serious problem of public health, the morbimortality related to the use of medicines; which on the other hand, exerts an important impact on the resources addressed to healthcare and on the individuals’ quality of life²⁴. The study may provide support for actions to implement pharmaceutical care programs that would have a positive effect on healthcare and prevent complications in patients with chronic diseases associated with hypertension²⁵.