FREQUENCY OF STATIN USE IN TYPE 2 DIABETICS HAVING
MACROVASCULAR DISEASE- AT A TERTIARY CARE HOSPITAL OF
KARACHI
Abdul Basit, M. Zafar Iqbal Hydrie, Rubina Hakeem,* M. Yakoob Ahmedani,
Qamar Masood
Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, & *R.L.A.K. Government College of Home
Economics Karachi
Background: During the last two decades with the introduction of statins large reductions in
cholesterol concentrations were easily and safely achievable and this led to studies that
demonstrated benefits of statin use. But only fewer than one fourth of adults with coronary heart
disease were receiving lipid-lowering drugs in a cross sectional health survey done in England.
Thus this study was designed to evaluate the frequency of statin use in type 2 Pakistani diabetic
subjects with macrovascular disease attending a tertiary care unit in Karachi, Pakistan. Methods:
Records of type 2 diabetic subjects coming to the outpatient department of Baqai Institute of
Diabetology and Endocrinology from September 1996 to December 2001 was analyzed for their
anthropometric and biochemical characteristics. Patients having any macrovascular disease were
identified and frequency of statin use by these subjects was studied. Results: Out of a total of
2152 patients 502 (252 males, 250 females) having macrovascular disease were identified. Only
16.5% of them (44 males, 39 females) were taking statins. Use of statins was higher amongst those
who had angina (20%) or myocardial infarction (17%) compared to those who had stroke (10%).
Sixty two percent of the users while 52% of the non-users had elevated blood cholesterol.
Conclusion: Frequency of statin use in the subjects studied was much lower than was warranted
with respect to their disease status. Presence of elevated blood cholesterol despite using statins
suggested inappropriate treatment in these subjects. Further studies are required to identify the
factors leading to low use of statins in type 2 diabetic subjects with macrovascular symptoms.
Keywords: Statin Users, Frequency, Lipid profile, Type 2 Diabetes, Pakistan, Macrovascular,
Angina, Myocardial Infarction, Stroke.
subjects with diabetes than those without it, hence the
INTRODUCTION
absolute benefits of statins appears to be larger in
diabetics. The ATP-III report by the National
Diabetic dyslipidemias are related to cardiovascular
Cholesterol Education Program (NCEP) lists high
disorders and also associated with the macrovascular
LDL levels to be the major cause of CHD and
complications
of
diabetes.
Macrovascular
diabetes is taken as CHD risk equivalent 11. United
complications are among the chief causes of major
Kingdom Prospective Diabetes Study (UKPDS) has
morbidity and mortality in people with diabetes 1-2.
also shown direct association of CHD risk with LDL
Diabetes has 3-5 times higher absolute risk of
levels among 3000 type 2 diabetic subjects and
coronary heart disease (CHD) death at each level of
inverse association with HDL Cholesterol 12.
blood cholesterol than non-diabetic subjects 3.
Heart Protection Study (HPS) has also
In the last 20 years studies have indicated
clearly shown that lowering lipid levels with a statin
that smoking cessation, beta blockers, anti-platelet
is of value in much broader populations than
agents, ACE-inhibitors and lipid lowering agents,
currently realized and all patients with vascular
each reduce the risk of vascular events to a moderate
4-7
disease or having CHD risk would benefit from
but important degree . With the introduction of
statins including those who were poorly represented
statins large reductions in cholesterol concentrations
in other studies such as elderly (>75 years of age),
were easily and safely achievable and this finding led
women, having LDL < 96 mg/dl, diabetics with no
to a series of studies that demonstrated benefits in
CHD and patients having stroke or peripheral
selected populations.
vascular disease 13.
Several large studies such as 4S8, CARE9
Thus it is universally recommended that
and LIPID10 have provided evidence for effectiveness
statins
should
be prescribed to all patients with
of lipid-lowering drugs in macrovascular disorders;
14
coronary
heart
disease
. Patients with myocardial
and have proven that lowering Low Density
infarction
(MI)
are
recommended
to use statins if
Lipoproteins (LDL) with statins reduces the risk of
180
mg/dl
and patients
their
total
cholesterol
was
>
CHD mortality and morbidity in high risk patients by
with angina should use statins if total cholesterol >
a quarter to half. The CHD risk was higher among the
200 mg/dl 15.
Though prescription of statins has increased
in recent years, it is still well below the
recommended level in the treatment of patients with
coronary disease in UK. In a cross sectional analysis
of data from health survey of England, only 19.9% of
adults with coronary heart disease were receiving
lipid-lowering drugs 15. There has not been any such
assessment of adequacy of use of lipid lowering
drugs in our country.
The purpose of this study was to assess the type 2
diabetics with macrovascular disease attending a
tertiary care unit in Karachi.
MATERIAL AND METHODS
Baqai Institute of Diabetology and Endocrinology
(BIDE) is a tertiary care hospital providing specialist
care to the diabetic population. ince its inception the
institute maintains computerized records of diabetic
patients. For this study computerized records of the
first visit of all type 2 diabetic subjects older than 18
years of age to the outpatient department of Baqai
Institute of Diabetology and Endocrinology from
September 1996 to December 2001 was analyzed for
their anthropometric and biochemical characteristics.
The information to be retrieved included computer
code, age, sex, occupation, place of residence, marital
status, family history, smoking, year of diagnosis of
diabetes and medications already being taken.
Therefore, minimal confidentiality or ethical issues
were involved. Furthermore names were not
disclosed anywhere and the researchers used only the
computer code for identification purposes.
Out of the total 2152 patients 502 subjects
having any macrovascular disease were identified
and frequency of statin use by these patients was
studied.
Glycemic control was assessed by fasting plasma
glucose and HbA1c.
Venous plasma glucose was estimated by GOD-PAP
Method16. HbA1c was assessed by DiaSTAT
Hemoglobin A1c Program, Bio-Rad17. HbA1c, was
used as the basic indicator of glycemic control.
Values of < 7%, 7 - 8.5% and > 8.5% indicated good,
fair or poor control respectively18. Where HbA1c
values were not available, fasting plasma glucose
values were used to determine glycemic control. FPG
<126, 126-144, and >144 were taken as good, fair
and poor control respectively18.
Total cholesterol and high density
lipoproteins were estimated by CHOD-PAP method
while triglycerides was estimated by GPO-PAP
method and low density lipoproteins values were
calculated 19. Values of total cholesterol > 200
mg/dl, triglycerides > 150 mg/dl, low density
lipoproteins > 130 mg/dl, high density lipoproteins <
40 mg/dl for males and < 50 mg/dl for females were
taken as abnormal 20.
Height and weight was recorded by the
medical officer with the help of height and weight
scale with subjects in light clothing and standing
without shoes. Height was recorded to the nearest
centimeters and weight to the nearest 0.1 kilogram.
Body mass index (BMI) was calculated by the
formula, weight in kilograms divided by height in
metres square (kg/m2). Obesity was taken as BMI >
25 kg/m2 as suggested by the International Obesity
Task Force21.
The OPD medical officer using a mercury
sphygmomanometer measured blood pressure once.
Hypertension was defined as B.P >130/85 mmHg or
isolated systolic & diastolic blood pressure of greater
than 130 & 85 mmHg respectively 22.
Patients with history of Ischemic Heart
Disease as evident by ECG changes or symptoms
deemed sufficient by the physician to be suggestive
of angina or MI were termed as sufferers of angina
and MI. Those suffering from any macrovascular and
Myocardial infarction were labeled in the group of
Myocardial infarction.
Patients with history of stroke evident by
signs & symptoms and physical examination as
assessed by the physician was termed as suffering
from stroke. Those if suffering from angina and
stroke were labeled in the group of angina.
Peripheral Vascular Disease (PVD) was
inferred from absent dorsalis pedis or posterior tibial
pulses with/without a history of intermittent
claudication. Those if suffering from angina and
PVD were labeled in group of angina. Those if
suffering from PVD and stroke were labeled in the
group of stroke.
Data entry and analysis
Data was entered and analyzed on SPSS 7.5.
ANOVA was used for estimating statistical
significance of differences in means of continuous
variables. Chi-square test was used to assess
statistical significance of difference in categorical
variables.
RESULTS
Out of total diabetics, 502 subjects (23.3 %) were
found to have any of the macrovascular symptoms
(MI, 24.9%; angina, 56.7%; stroke, 15.7%; PVD,
2.6%). All available bio-chemical parameters were
analyzed and mean values are given in table-1. Only
16.5% of the patients were using any statins. Though
the difference was not statistically significant the use
was slightly higher among males (17.5%) as
compared to females (15.6%) (Table-2). Among
older subjects (>60 years of age) 18.6% were using
statins whereas in those less than 60 years the use of
statins was around 15%. This difference was also
statistically non significant. In terms of
socioeconomic status use of statins was slightly
higher among businessmen and professionals (20%
of all businessmen and professionals)) as compared
to skilled workers (15.7% of all skilled workers) and
housewives (15.6% of all housewives). In relation to
vascular disease the use of statins was most frequent
among the angina sufferers (20%), followed by those
who had MI (16.9%), followed by stroke sufferers
(10%) while none of the peripheral vascular disease
sufferers were using statins (Table-3).
Table 1: Characteristics of the Sample
Male
Mean + SD
Age (years)
57.5 + 10.2
Weight (Kgs)
70.0 + 11.1
Height (metre)
1.70 + 0.1
Body Mass Index 25.3 + 3.5
(Kg/m2)
Systolic
Blood 131.6 + 22.4
Pressure (mmHg)
Diastolic
Blood 81.4 + 11.8
Pressure (mmHg)
Cholesterol (mg/dl) 197.2 + 47.8
Triglycerides (mg/dl) 191.3 + 131.6
Low
Density 122.6 + 42.7
Lipoproteins (mg/dl)
High
Density 37.7 + 9.0
Lipoproteins (mg/dl)
Fasting
Plasma 190.8 + 80.1
Glucose (mg/dl)
Random
Plasma 256.0 + 92.4
Glucose (mg/dl)
HbA1c (%)
8.7 + 2.3
Female
Mean + SD
55.9 + 9.7
63.2 + 12.4
1.50 + 0.1
27.1 + 5.0
140.8 + 24.6
82.1 + 13.0
206.5 + 45.8
192.9 + 103.9
131.4 + 47.4
37.9 + 11.0
199.6 + 86.2
262.5 + 105.0
9.2 + 2.3
Table 2: Statin use according to sex of Subjects
Statin Use
Yes
Male
(n=252)
Female (n=250)
Total (n=502)
No
44(17.5% )
39(15.6%)
83(16.5% )
208(82.5% )
211(84.4%)
419(83.5%)
Table 3: Statin Use according to Macrovascular
disease of patients
Statin Use
Yes
Angina (n=285) 55(20.0%)
MI (n=125)
20(16.9%)
No
230(80.0%)
105(83.1%)
Stroke (n=79)
8(10.0%)
71(90.0%)
PVD (n=13)
0(0.0%)
13(100.0%)
The users of statins had higher values for
triglycerides, total cholesterol and LDL-C and lower
mean values for HDL-C (figure 1).
DISCUSSION
The results of this study shows a trend which has also
been reported by other researchers i.e under
prescription of statins 23-24.
Only one fourth of diabetic subjects with
macrovascular disease were taking statins for their
lipid control. As the duration of treatment for which
statins had been prescribed is not known, comments
on the effect of use of statins could not be given. The
presence of higher proportion of subjects with
diabetic dyslipidemia in the statins user group could
be either due to the short period since
commencement of medication when they presented at
BIDE or that they were under-dosed.
Though the differences in the characteristics
of the users and non-users did not reach statistical
significance the results of this study indicates that
males, relatively more affluent, older diabetics, those
having angina and having elevated triglycerides are
more likely to get treated by statins. Although the
subjects presenting at BIDE are from a relatively
narrow range of socioeconomic status, housewives
seem to be less likely to be started on statin. This
trend of females not been started on statins has also
been seen in other studies 24-26.
The Health Survey for England and the
British Regional Heart Study suggested that most
older men with CHD are not receiving lipid lowering
drug treatment while in our study the elderly
diabetics with CHD were proportionally more on
statin treatment; probably as younger subjects were
put on diet & exercise and not considered for statins
as a first line therapy by the physicians 27.
It is surprising that subjects with angina
were more on statins as compared to MI a reverse
trend as seen in studies elsewhere. This highlights the
fact that subjects with MI were not given statins as a
part of therapy irrespective of lipid levels; perhaps
having normal lipid levels post MI been a reason for
their not been started on statins. Angina patients have
a high absolute risk of acute coronary events and
silent MI in diabetics advocates for earlier treatment
with statins 24-25.
In subjects with type 2 diabetes blood
triglycerides tend to be raised and HDL levels
reduced even with good metabolic control while LDL
levels tend to be similar to those seen in the general
population. This has contributed to the belief that
LDL is of little relevance to the risk of CHD in
diabetics and thus most people with diabetes do not
receive lipid lowering drugs despite their increased
risk.
The statin user group in our study had
markedly higher mean values for triglycerides, total
cholesterol & LDL and slightly lower value of HDL.
It is suggested that either the subjects were recently
prescribed statins or higher doses of the drugs are
required in these patients to achieve target lipid
levels; both of which could not be verified in this
study. By retrieving and analyzing data from a larger
and more heterogeneous group of subjects validity of
these trends could be verified.
For the current analysis information about
previous physicians was not available so any trends
in the use of statins by various physicians could not
be explored. However despite the clear efficacy of
statin use it seems likely that physicians may vary in
their knowledge, attitudes and practices regarding the
use of statins.
The very low statin prescribing rate in CHD subjects
is a cause for concern especially as type 2 diabetic
subjects has high morbidity and mortality11. Thus
there is a need to review the treatment of all diabetic
patients with CHD and make sure that patients are
receiving the benefits of starting treatment as early as
possible.
Barriers to a more wide spread use of statins
may include fears about the cost resulting in nonaffordability as well as clinical practices. Since 80%
of CHD occurs in developing countries it should be a
priority to make latest recommendations such as ATP
III Report accessible to the physicians14. Physicians
are aware about the potential gains from the currently
available preventive strategies and it is hoped that
enough studies have been done to convince
physicians that statins should be prescribed for the
vast majority (if not all) diabetic patients with CHD
in both primary and secondary care.
In conclusion the results of this study verify
the low prescribing rates of statins in our community
setting. In view of possible detrimental impact of this
trend, further studies are needed to identify the
factors leading to low use of statins in type 2 diabetic
subjects with macrovascular symptoms to ensure that
patients receive this treatment which will lead to
clinical and public health benefits.
Figure-1: Prevalence of lipid abnormalities according to Statin use
ACKNOWLEDGMENT
2.
3.
We acknowledge the co-operation of PharmEvo
Pakistan for providing financial support to the
Research department, BIDE.
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______________________________________________________________________________
Address For Correspondence:
Dr M. Zafar Iqbal Hydrie, Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi.
Phone: +92-21-6612128 (Res.), 6617234-5 (Off.)
Email: bideresearch@hotmail.com