Download Antihypertensive drug use in diabetics

Antihypertensive drug use in diabetics - A drug utilization study
Dr. R.P.Limaye
Department of Pharmacology, Bharati Vidyapeeth DU Medical College & Hospital,
Sangli, Maharashtra, India
Dr. M.M.Ghaisas
Department of Pharmacology, SCE’s Indira College of Pharmacy,
Pune, Maharashtra, India
Ms. S.A.Naik Department of Pharmacology, SCE’s Indira College of Pharmacy,
Pune, Maharashtra, India
Ms. M.S.Kadam
Department of Pharmacology, SCE’s Indira College of Pharmacy,
Pune, Maharashtra, India
Mr. R. Sonawane
Department of Pharmacology, SCE’s Indira College of Pharmacy,
Pune, Maharashtra, India
Corresponding Author: Dr. R.P.Limaye
E-mail: [email protected]
Department of Pharmacology, Bharati Vidyapeeth DU Medical College & Hospital,
Sangli, Maharashtra, India
Running title: Antihypertensive utilization in diabetics
Abstract
Introduction and Background: Diabetes is a multisystem metabolic disorder
complicated by concurrent presence of hypertension. Patients with both disorders
have multifold chances of developing complications. Appropriate treatment of
hypertension is known to reduce the prevalence of this occurrence. Hence the study
was planned to study the antihypertensive drug utilisation in diabetics. Such drug
utilization studies help in providing evidence for intervention in present therapeutic
trends.
Methods: Observational study, carried in consenting patients from the database of
tertiary care hospitals in Pune and Sangli from September 2013 to January 2014. In a
predefined format information regarding use of drugs was recorded. No personally
identifiable information was collected.
Results: Majority of patients were from age group 61-70. Most prescribed drug was
angiotensin II receptor inhibitors, in combination calcium channel blockers were most
prescribed.Only 6% received aspirin while 13% lipid lowering agents.
Conclusions: Majority of the patients received Angiotensin receptor blockers in
single drug and calcium channel blockers in multidrug treatments. This pattern did not
exactly followed the present guidelines but was not irrational. However use of aspirin
and lipid lowering agents was very low compared to expectations and guidelines.
Keywords: antihypertensives, diabetics, drug utilization
Introduction
Diabetes is a chronic metabolic disorder which is characterised by high blood sugar
level, either because the pancreas does not produce enough insulin, or because cells
do not respond to the insulin that is produced. Diabetes and hypertension frequently
occur together. Hypertension and diabetes are two of the leading risk factors for
atherosclerosis and its complications, including heart attacks and strokes. They share
certain physiological traits – that is, the effects caused by each disease tend to make
the other disease more likely to occur, some of these effects include: Increased fluid
volume –Increased arterial stiffness - Impaired Insulin Handling – Changes in the way
the body produces and handles insulin can directly cause increase in blood
pressure.1,2,3
Hypertension (defined as a blood pressure ≥140/90 mmHg) is an extremely common
comorbid condition in diabetes, affecting 20–60% of patients with diabetes,
depending on obesity, ethnicity, and age. In type 2 diabetes, hypertension is often
present as part of the metabolic syndrome of insulin resistance also including central
obesity and dyslipidemia. In type 1 diabetes, hypertension may reflect the onset of
diabetic nephropathy. Hypertension substantially increases the risk of both
macrovascular and microvascular complications, including stroke, coronary artery
disease, and peripheral vascular disease, retinopathy, nephropathy, and possibly
neuropathy.4,5,6
In recent years, adequate data from well-designed randomized clinical trials have
demonstrated the effectiveness of aggressive treatment of hypertension in reducing
both types of diabetes complications. Diabetes increases the risk of coronary events
twofold in men and fourfold in women. Part of this increase is due to the frequency of
associated cardiovascular risk factors such as hypertension, dyslipidemia, and clotting
abnormalities. 7,8,9
In observational studies, people with both diabetes and hypertension have
approximately twice the risk of cardiovascular disease as nondiabetic people with
hypertension. Hypertensive diabetic patients are also at increased risk for diabetesspecific complications including retinopathy and nephropathy.
Hence it is essential to monitor the prescribing pattern of antihypertensive drugs in
patients suffering from diabetes and hypertension with respect to monotherapy,
multitherapy, use of FDC’s etc to avoid further complications.9,10,11,12,13
Methods
The antihypertensive drug prescribing pattern data was collected from the patients
who were included in this study according to the inclusion and exclusion criteria,
from September 2013 to January 2014.
STUDY DESIGN: Observational study
STUDY PERIOD: Five months
STUDY PLACE: Pimpri Chinchwad, Pune.
SAMPLE DESIGN: Random purposive sampling.
INCLUSION CRITERIA : .
Patients consenting to participate in the study
Patients having diabetes and hypertension and no other disease.
EXCLUSION CRITERIA :
Patient suffering from any other disease in addition to diabetes and hypertension.
Results
Agewise distribution of patients Table-1
It was observed that diabetes and hypertension largely occurs in patient of 61-70 yrs
(30.61%)
It was observed that AT II Blockers (30%) were prescribed mainly by the physician –
Table 2
It was observed that combination of (calcium channel blocker + AT II Blocker)
32.25% were mainly prescribed by physician (Table no .3)
Fixed Dose Combination use-It was observed that fixed dose combinations of
(Calcium channel blockers +AT II Blocker) 45.45% were mainly prescribed -(Table 4)
It was observed that in only 6% cases aspirin was prescribed
It was observed that in only 13.11% cases lipid lowering drugs were prescribed.
DISCUSSION
Diabetes increases the risk of coronary events twofold in men and fourfold in women.
Part of this increase is due to the frequency of associated cardiovascular risk factors
such as hypertension, dyslipidemia, and clotting abnormalities. In observational
studies, people with both diabetes and hypertension have approximately twice the risk
of cardiovascular disease as nondiabetic people with hypertension. Hypertensive
diabetic patients are also at increased risk for diabetes-specific complications
including retinopathy and nephropathy. 1-4,6,7,8
There are a number of trials demonstrating the superiority of drug therapy versus
placebo in reducing outcomes including cardiovascular events and microvascular
complications of retinopathy and progression of nephropathy. These studies used
different drug classes, including angiotensin-converting enzyme (ACE) inhibitors,
angiotensin receptor blockers (ARBs), diuretics and β-blockers, as the initial step in
therapy. All of these agents were superior to placebo; however, it must be noted that
many patients required three or more drugs to achieve the specified target levels of
blood pressure control. Overall there is strong evidence that pharmacologic therapy of
hypertension in patients with diabetes is effective in producing substantial decreases
in cardiovascular and microvascular diseases.1,6,13 The study of patterns of
antihypertensive use in patients with diabetes and hypertension was done to evaluate
whether they were consistent with evidence-based practice guidelines.15,16,17
In monotherapy AT ll blockers were prescribed maximum. In 2001, evidence from
several trials and meta-analysis clearly suggested that ACE inhibitors are better than
any other class of antihypertensive in protecting against progressive renal damage.
According to the analysis in about 18 % cases ACEI’s were prescribed
The rising use of ACE inhibitors may be explained by their substantial benefits in
congestive heart failure and diabetes as JNC VI recommends this drug class as the
first-line treatment for hypertensives with these conditions. Studies demonstrate the
benefits of ACE inhibitors on multiple adverse outcomes in patients with diabetes,
including both macrovascular and microvascular complications, in patients with either
mild or more severe hypertension and in both type 1 and type 2 diabetes, the
established practice of choosing an ACE inhibitor as the first-line agent in most
patients with diabetes is reasonable. The use of angiotensin-converting enzyme
inhibitors (ACEI) can prevent the progression of renal damage and delay progression
to end-stage renal disease in addition to lowering BP. Thus, it has been suggested that
all diabetic patients with BP greater than 130/80 mm Hg should begin ACEI treatment
unless contraindicated.18,19,20,21,22,23
In patients with microalbuminemia or clinical nephropathy, both ACE inhibitors and
ARBs are considered first-line therapy for the prevention of and progression of
nephropathy. However, other strategies including diuretic and β-blocker–based
therapy are also supported by evidence.23,24
It was also observed that non selective β blockers were prescribed in some cases. But
according to JNC 8,nonselective β blockers should not be prescribed in diabetic
patients as they mask the hypoglycaemic effects in patients.
Hypertension is a major risk factor for stroke, heart failure, coronary heart disease,
and end-stage renal disease. Hypertension is also commonly associated with diabetes
and chronic renal failure generally. For management of hypertensives with these
comorbidities, both JNC VI and JNC VII guidelines recommend ACE inhibitors as the
preferred drug for hypertension in the setting of CKD, diabetes, or congestive heart
failure; ACE inhibitors or diuretics for recurrent stroke prevention; and β-blockers for
those with prior myocardial infarction.21,22,23
Berlowitz et al, 2005, have shown worse BP control in patients with diabetes and
less intensive anti-hypertensive medication therapy. Use of multiple drugs in
combinations is being increasingly recognized as critical to control hypertension in
patients with diabetes.5
According to the analysis Combination of Calcium channel blockers+AT II blockers
were maximum prescribed as per the JNC VIII guidelines. Also combination of
Calcium channel blockers+ diuretics were prescribed as per JNC 8 guidelines. As per
the guidelines the combination of ACE inhibitors and AT II blockers were not seen to
be prescribed.
Recently, several large clinical trials demonstrated that most patients with
hypertension can achieve and sustain adequate blood pressure control only with the
use of multiple antihypertensive drugs. Initiating drug therapy with a diuretic, either
alone or in combination with an agent from another drug class apparently provides the
best outcomes for hypertension management as per the findings have been
incorporated into the current JNC VII and JNC VIII guidelines.
Unacceptable combinations are non-dihydropyridine calcium blockers (such as
verapamil or diltiazem) and beta-blockers, dual renin–angiotensin system blockade
(e.g. angiotensin converting enzyme inhibitor + angiotensin receptor blocker), renin–
angiotensin system blockers and beta-blockers, beta-blockers and centrally acting
agents. Combinations of an ACE-inhibitor or angiotensin II–receptor antagonist, a
diuretic and an NSAID (including selective COX-2 inhibitors and non-prescribed
drugs such as ibuprofen) should be avoided whenever possible due to a high
documented risk of acute renal failure.
Calcium channel blockers+ AT II blockers were the maximum prescribed
combinations in FDC. Fixed-dose combination (FDC) therapies offer a means to
simplify complex treatment regimens, and have several advantages that help patients
reach their glycaemic goals. Some key benefits are identified and discussed in support
of FDCs for treatment of patients by researchers are19,20

Greater efficacy compared with higher dose monotherapy

Reduced risk of adverse reactions relative to higher dose monotherapy

Lower overall costs and

Improved medication concordance.
Aspirin has been found to be of benefit overall in those at low risk of heart disease as
the risk of serious bleeding is equal to the benefit with respect to cardiovascular
problems because aspirin has antiplatelet properties. As per the observation only in
6% cases aspirin was prescribed.
Statins are effective in preventing further cardiovascular disease in people with a
history of cardiovascular disease. In those without cardiovascular disease but risk
factors statins appear to also be beneficial with a decrease in mortality and further
heart disease. Lipid lowering drugs also can be prescribed as they help in reducing the
elevated blood pressure by acting on the cholesterol levels. Hypercholesterolemia is a
primary risk factor for cardiovascular disease. Large-scale randomized trials have
shown that lipid-lowering with HMG-CoA reductase inhibitors (statins) reduce
relative risk for cardiovascular events or death both in primary and in secondary
prevention).
Therefore,
statins
are
widely
used
for
the
treatment
of
hypercholesterolemia. The time course over which statins provide prevention against
death appears to be long, of the order of one year, which is much longer than the
duration of their effect on lipids, a hypothesis put forth by Borghi et al.
12
In the
present study only 13.11% cases were prescribed with lipid lowering drugs .
Despite evidence that aggressive lowering of BP in people with diabetes reduces
cardiovascular morbidity and mortality, it was found that BP control in individuals
with diabetes is suboptimal, with fewer than one in eight patients having BPs
controlled to the levels currently suggested by hypertension and diabetes guidelines
.Further, systematic review revealed that this suboptimal treatment pattern, at least in
the 44 studies from 19 countries we identified, is not restricted to certain locales or
physician specialties.8
As per World Health Organization, around 31.7 million individuals in India were
affected by diabetes during the year 2000 which may further rise to 79.4 million by
the year 2030. Diabetes mellitus (DM) is the chronic disorder emerging as major
health problem which increases the rate of morbidity and mortality. Poor management
of these two disorders leads to several complications. Management of DM requires
both pharmacological and nonpharmacological interventions. Hypoglycemia is the
common adverse drug reaction (ADR) of antidiabetic drugs and it is associated with
substantial morbidity and mortality. In this regard drug utilization study was
conducted to determine the drug utilization pattern of antidiabetic medicines during
hospital stay and at the time of discharge, cost of antidiabetic drugs and defined daily
dose (DDD)/100 bed-days during hospital stay in our setup. Adverse drug reactions
(ADRs) related to antidiabetic medicines were also monitored during hospital stay.
18
In developing countries such as India, the focus for long has been on the control of
acute and chronic infections and communicable diseases. Mortality data from Global
Burden of Diseases Studies has revealed that cardiovascular diseases, especially
coronary heart disease are important causes of death. Worldwide, of the 17.5 million
deaths from cardiovascular diseases, 20% deaths ocurred in high income countries,
8% in upper-middle income countries, 37% in lower-middle income countries and
35% in low income countries including India. In many regions of these countries
cardiovascular diseases, especially coronary heart disease, are more prevalent among
the illiterate and low socioeconomic subjects. Recent case-control studies in India
have reported that being illiterate or poor is an independent risk factor for acute
myocardial infarction. Many of the standard coronary risk factors such as smoking
and tobacco use, low physical activity, high dietary fat intake, uncontrolled
hypertension, uncontrolled hypercholesterolemia and diabetes are also more.11
CONCLUSIONS
Interpretation of our results must be considered along with recognition of several
limitations of the study. First, our study is retrospective and was conducted at some
tertiary care hospital.
In conclusion, findings suggest that ARB was prescribed in maximum patients but as
per the JNC VIII guidelines the thiazide diuretics should be the first line treatment in
hypertension with diabetes. Thus it was observed that the guidelines for treatment
were not exactly followed.
Anti-hypertensive use in multidrug regimens was generally consistent with JNC VIII
guidelines, those being the current guidelines at the time of our study.
It was also observed that β blockers were prescribed in some cases. But according to
JNC VIII, β blockers should not be prescribed in diabetic patients as they mask the
hypoglycaemic effects in patients.
Calcium channel blockers+ AT II blockers were the maximum prescribed
combinations in FDC as per the guidelines.
Conflict of interest
The authors have no conflicts of interest.
Financial Support
This study was self funded.
References
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…
TABLES
Table 1 - Age wise drug use distribution
It was observed that diabetes and hypertension largely occurs in
patient of 61-70 yrs
(30.61%) followed by
Age in years
Percentage
< 30
2
31-40
8.64
41-50
17.28
51-60
23.45
71-80
14.81
81-90
3.7
(Table no. 1)
Table 2-Category wise drug use distribution
It was observed that AT II Blockers (30%) were prescribed mainly by
the physician followed by
Category of drug
Percentage%
Calcium channel blockers
22
ACE Inhibitors
18
Diuretics
14
β Blockers
8
K+ opener
2
(Table no 2)
Table 3- Combination drug use distribution
It was observed that combination of (calcium channel blocker + AT II
Blocker) 32.25% were mainly prescribed by physician followed by
Category of drug
Percentage
AT II Blocker +Diuretics
25.80
ACE Inhibitors +Diuretics
9.67
B blocker + Calcium channel blocker
9.67
Calcium channel blocker + ACE Inhibitor
6.45
AT II Blocker +ACE Inhibitors
6.45
Calcium channel blocker+ Diuretics
6.45
B Blocker +AT II Blocker
6.45
(Table no .3)
Table 4- FDC drug use distribution
It was observed that fixed dose combinations of
(Calcium channel blockers +AT II Blocker) 45.45% were mainly
prescribed followed by
Category of drug
Percentage(%)
β blockers + diuretics
27.27
ACE inhibitors+ diuretics
18.18
AT II blocker + diuretics
9.09
(Table no 4)
Charts placed here
1 Agewise distribution of patients
2 Pattern of drug utilisation - monotherapy
3 Pattern of drug utilisation – multitherapy
4 Pattern of drug utilisation - FDC
5 Use of aspirin
It was observed that in only 6% cases aspirin was prescribed
6 Lipid lowering drugs prescribed or not
It was observed that in only 13.11% cases lipid lowering drugs
were prescribed.