A journal club on the Practice of Indian Physicians Towards Use of Calcium Channel Blockers in the Management of Hypertension A Paper Based Questionnaire Survey, research.

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Presented by,
Mahdy Ali Ahmad Osman
Pharm.D Intern
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2. Practice of Indian Physicians Towards Use of
Calcium Channel Blockers in the Management of
Hypertension : A Paper Based Questionnaire
Survey
Kalpesh Dalvi, Medical Advisor,
Abhijit Trailokya, Chief Manager, Medical Affairs,
Kamlesh Patel, General Manager, Medical Affairs
— Abbott Healthcare, Mumbai, Maharashtra, India.
ARCH INTERN MED/VOL 172 (NO. 2), JAN 23, 2012
Indian Medical Gazette — JANUARY 2015 2

3. ABSTRACT
Background: Hypertension is a prevalent condition. Improving blood pressure
control would depend on understanding concerns and limitations of physicians.
Objective: Understanding practice of calcium channel blockers use among
physicians.
Material and methods: A cross-sectional, observational paper based questionnaire
survey among 218 Indian physicians.
Results: According to 55.83% of physicians (n=218), prevalence of hypertension
ranges between 21-40%. Sixty percent physicians get referred cases mostly from
the general physicians (69.48%). More than 20% patients have concomitant illness
according to 33.81% physicians, most common being diabetes (33.44%).According
to 96.30% physicians, due to asymptomatic nature, hypertension remains
undiagnosed, untreated and uncontrolled. Stress (32.35%), obesity (23.13%),
physical inactivity (22.78%) and smoking (20.52%) are responsible for sympathetic
over activity. Calcium channel blockers (CCBs) (37.19%), beta blockers (30.43%),
angiotensin receptor blocker (ARB) (12.14%) and angiotensin converting enzyme
(ACE) inhibitors (4.02%) are used as first choice in patients with sympathetic over
activity. Ischemic event, stroke, heart failure and renal failure occur due to ignoring
sympathetic over activity according to 30.91%, 25.39%, 20.97% and 22.30%
physicians respectively. 3

4. • According to 51.63% of physicians, patient compliance to
antihypertensive therapy is > 70%. Lack of awareness (40.5%) and
dosage frequency (24%) are two most common reasons for
noncompliance. According to 89.72% of physicians, the current CCBs
primarily inhibit L-type calcium channels but cause sympathetic over
activity. A total of 48.34% physicians, >10% patients complain of pedal
edema with amlodipine. In physicians opinion, blockage of L and N type
of calcium channels (56.47%), unique mode of action (11.76%),
arteriolar and venous dilation (9.41%) and inhibition of
reninangiotensin- aldosterone (RAS) system (7.06%) are responsible for
less pedal edema with cilnidipine. A total of 98.7% and 99.54%
physicians rated efficacy and safety of cilnidipine as “good-very good”
compared to other CCB respectively.
• Conclusion: In hypertension, sympathetic over activity may cause many
complications. As per the physicians opinion survey, cilnidipine because
of its unique mechanism of action offers multiple benefits in
hypertensive patients and can be preferred over amlodipine.
• Keywords:hypertension, sympathetic over activity, physicians based
questionnaire survey, calcium channel blocker, cilnidipine.

5. • Hypertension, a common chronic disease worldwide is a major risk factor
for cardiovascular disease. The problem of hypertension in India is soaring
with reported prevalence in urban and rural population about 25% and 15%
respectively. Treating this highly prevalent condition without significant
adverse events is very important. Though some hypertensive patients may
consult cardiologist, nephrologist or endocrinologist directly, but general
physicians also play a very important role in the management of
hypertension in India. Secondly, cooperation of patients also plays a critical
role in the management of hypertension. For the treatment of hypertension,
various classes of antihypertensive agents such as angiotensin converting
enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs),
calcium channel blockers (CCB), beta blockers, diuretics, and their
combinations are available in India. The selection of one drug over the
other may depend on various factors including patient profile, age,
associated comorbid conditions, cost of therapy, side effects etc. We
believed that improving control of increased blood pressure in clinical
practice would depend on understanding the concerns of physicians and
limitations in the management of hypertension mainly related to
pharmacotherapy and trying to provide solutions for these concerns and
limitations. 5
Introduction

6. • To understand the approach and practice of using calcium channel
blockers in the treatment of hypertension among physicians in India.
6
Objective

7. MATERIALS AND METHODS
A cross-sectional, observational questionnaire-based survey was
conducted among 218 physicians in India. The duration of this survey
was from June 2013 to December 2013. The physicians practicing
independently and in the hospitals in metro and tier I cities were
included in the survey. The study participants were provided a paper
based questionnaire survey format comprising of four sections;
epidemiology, approach to diagnosis and management of
hypertension, use of CCBs and cilnidipine 5 and 10 mg. The
physicians willing to fill the complete survey format were enrolled.
The overall information regarding the approach to the management of
hypertension while using antihypertensive agents with focus on CCBs
was collected.
The filled survey forms were returned by the physicians with the
medical representatives.
7

8. • Number of responses to each question was categorized
and percentages for all the responses were calculated.
Missing data was not considered for calculating
percentages.
Statistical Analysis

9. RESULT
9
•Total 218 physicians were enrolled in this survey. The results of the survey are
only subjective, recording opinion of physician based on their clinical
experience and practice. According to 55.83% of physicians, the prevalence of
hypertension in India ranges between 21-40%. Most of the physicians (80.18%)
see more than 20 hypertensive patients in a month. Only 6.14% physicians see
about 6-10 patients per month while 13.36% physicians see between 11-20
patients per month. The number of physicians treating hypertensive patients in
different age groups was almost similar. A total of 25.63% of physicians treat
patients between age group of 40-50 years and 50-60 years each.
The number of physician treating hypertensive patients between 60-70 years and
>70 years were 25.13% and 23.62% respectively. Most of the physicians
(73.92%) come across more than ten percent newly diagnosed patients in their
practice while remaining physicians treat less than ten percent of newly
diagnosed cases of hypertension. Sixty percentage of physicians get referred
cases of hypertension while others 39.37% physicians seen hypertensive patients
directly. Most of the cases are referred by general physicians (69.48%) or
consulting physicians (17.53%) while others are referred by the other specialties
e.g. gynecologists etc.

10. • The percentage of pre-hypertensive (32.10%), stage 1 (34.18%) and
stage 2 (33.72%) hypertension is approximately same among newly
diagnosed hypertensive cases (Fig. 1).
• Concomitant illness is often observed in patients with hypertension.
More than 20% patients have concomitant illness according to 33.81%
physicians. Less than 5% cases have concomitant illness according to
9.05% physicians while according to 28.57% physicians, 6-10% and 11-
20% of the patients have concomitant illness. In stage 1 hypertensive
patients, the most common illness is diabetes (33.44%) followed by
coronary heart disease (25.86%), chronic kidney disease (23.23%) and
heart failure (15.65%) (Fig. 2).
• Most of the physicians (96.30%) physicians agree that in many patients
due to asymptomatic nature, hypertension remains undiagnosed,
untreated and uncontrolled. Similarly, according to 97.71% physicians,
sympathetic over activity is one of the major causes for hypertension.
Stress (32.35%), obesity (23.13%), physical inactivity (22.78%) and
smoking (20.52%) are the major reasons for sympathetic over activity
(Fig. 3).
• According to 79.25% physicians sympathetic over activity is present in
up to 50% of the newly diagnosed patients with hypertension. A total of
18.40% and 2.36% of physician believe that sympathetic over activity is
present in about 51-75% and 76-100% newly diagnosed hypertensive
patients.

13. • Amongst antihypertensive drugs, ACE inhibitors, ARBs, CCBs and beta blockers are used
for the management of hypertension with sympathetic over activity by 23.72%, 24.54%,
24.74% and 24.54% physicians respectively. Calcium channel blockers (37.19%), beta
blockers (30.43%), ARBs (12.14%) and ACE inhibitors (4.02%) are first choice for the
management of hypertensive patients with sympathetic over activity amongst
antihypertensive drugs and Beta blockers (26.09%), CCBs (23.97%), ARBs
• (19.90%) and ACE inhibitors (19.4%) are used as second choice agent in the management
of hypertensive patients with sympathetic over activity. Ischemic events, stroke, heart
failure and renal failure are the consequences of ignoring sympathetic over activity in
patients with high blood pressure according to 30.91%, 25.39%, 20.97% and 22.30%
physicians respectively (Fig. 4).
• First three indications for the use of calcium channel blockers are elderly patients (36.27%),
isolated systolic blood pressure (23.53%) and diabetes (11.27%).
• According to 51.63% of physicians, the compliance rate in hypertensive patients is more
than 70% while remaining physicians feel, the compliance rate is less than 70%.
• The most common reason for non-compliance is lack of awareness (40.5%) while second
most common reason is dosage frequency (24%). The other causes of noncompliance in
hypertensive patients are lack of visible advantages of medicine to the patient (18%) and
precautions to be taken while taking medicines (12%) (Fig. 5).
• A total of 76.78% physicians preference use of CCB only in established cases of
hypertension with sympathetic over activity because of less side effects (46.67%), good
efficacy (26.67%), once daily dosage/long duration of action (11.11%) or cost (8.89%).

15. • The four most common benefits considered by the physicians while prescribing
CCBs are safety/tolerability profile of the agent (30.24%), blood pressure control
(27.42%), compliance (6.05%) and cost (4.44%).
• According to most of the physicians (89.72%), the current CCBs primarily inhibit
L-type calcium channels and reduce blood pressure, but they stimulate sympathetic
nerve activity leading to reflex tachycardia.
• The five most common patients profiles where cilnidipine 5/10 mg is used in the
management of hypertension are elderly patients (>50 yrs) (12.03%), diabetic
hypertensive patients (10.79%), all hypertensive patients (10.37%), young
hypertensive (6.64%) and stage 1 hypertension (6.64%)
• The dose of cilnidipine used ranges between 5 to 40 mg per day mostly once daily
(73.21%) or twice daily (26.79%). Most of the physicians (62.64%) use cilnidipine
for one month to one year while 10.44% physicians believe that it needs to
continue for long time. A total of 8.79% physicians consider it needs to be given for
life long.
• A total of 48.34% physician mentioned that >10% patients complain of pedal
edema with amlodipine while 29.86% physicians said, pedal edema is seen in 5-
10% of patients. Almost all (99.52%) physicians feel that introduction of
cilnidipine would minimize the incidence of pedal edema.

16. • Blockage of L and N type of calcium channels (56.47%), unique mode of
action (11.76%), arteriolar and venous dilation (9.41%) and inhibition of
rennin-angiotensinaldosterone system (7.06%) are the four important
reasons recognized by the physicians responsible for less pedal edema with
cilnidipine.
• According to 48.08% of the physicians >36% patients who were
prescribed cilnidipine showed satisfactory control of blood pressure. Most
of the physicians (96.67%) agree that cilnidipine helps to increase the
compliance in hypertensive patients because of reduced ankle edema
(33.53%), no or less side effects (21.56%), once daily dosage (13.77%),
good blood pressure control (8.98%) and less or no reflex tachycardia
(7.19%).
• Most of the physicians 98.7% rated efficacy of cilnidipine as “good-very
good” compared to other CCB. Similarly, 99.54% physicians rated the
safety of cilnidipine as “good-very good” (Table 1).
• The dilatation of efferent and afferent arterioles, reduction of glomerular
pressure and rennin secretion and reduction of proteinuria were reported as
properties responsible for reno-protection with cilnidipine by 87.50% of
the physicians (Table 2).

18. DISCUSSION
18
•More than 20% physicians use ACE inhibitors, ARB, calcium channel blocker (CCBs)
and beta blockers for the management of hypertension with sympathetic over activity.
CCBs are widely used in the treatment of hypertension6. CCBs are used more than beta
blockers, ARB and ACE inhibitors as first choice in hypertensive patients with
sympathetic over activity. However, it should be noted that because of complications of
increased sympathetic tone dihydropyridine type of calcium channel blockers with slow
onset of action without reflex activation of the sympathetic tone should be used5. L/N-
type calcium channel blockers have sympatholytic action7. Cilnidipine is a L/N-type
CCB, used in the treatment of essential hypertension 8 which has a slow onset but long-
lasting action.
•Chronically elevated sympathetic tone may cause adverse impact on heart, kidney and
blood vessels. The results of such sustained sympathetic over activation can lead to
ischemia, heart failure, hypertrophy, stroke and atherosclerosis. Large number of
physicians in this study agreed that ignoring sympathetic over activity may lead to
ischemic event, stroke, heart failure and renal failure.
•Non-adherence to medications is a major concern in the management of chronic disease
such as hypertension10,11. Close to half of the physicians in this study reported that
compliance rate in hypertensive patients is less than 70%.
•Patients’ levels of hypertension awareness is low1, which has been seen both in urban
and rural patients in India2. Lack of knowledge is associated with noncompliance12.

19. • In this study also, the most common reason for noncompliance reported is lack of
awareness followed by dosage frequency of antihypertensive agents. Lesser frequency of
administration may help to improve the patient compliance. Cilnidipine can be used once
or twice daily13. Education of patients about disease and its management also helps to
improve adherence which results in improved treatment outcomes14.
• Most of the physicians believe that the current calcium channel blockers primarily inhibit
L-type calcium channels, but cause reflex tachycardia because of the stimulation of
sympathetic nerve activity. In this regards, L/N-type calcium channel blockers such as
cilnidipine have an advantage because of the sympatholytic action7.
• Calcium channel blockers are associated with risk of peripheral edema as a side effect
which may reduce patient compliance 15. Amlodipine is an L-type calcium channel
blocker (CCB) which causes ankle edema as a common adverse effect 8. Many physicians
mentioned patients often complain of pedal edema with amlodipine. Use of cilnidipine
may minimize pedal edema, because of the unique mechanism of action such as blockage
of L and N type of calcium channels. L/N-type calcium channel blockers have reno-
protective effect because of the dilation of afferent and efferent arterioles of the renal
glomerulus. The L/N type calcium channel blockers provide better protection against
organ damage compared to L-type calcium channel blockers in hypertension7. In the
hypertension, protection against organ damage with L/N type calcium channel blockers is
better compared to L-type calcium channel blockers7. Cilnidipine inhibits renal RAS,
protects podocytes 6 and prevents development of proteinuria16. Renoprotective effects of
cilnidipine are induced via mechanisms independent of renal sympathetic nerve
inhibition6.

20. Limitations
• The study has some limitations:
• First, it was a cross sectional survey and the responses were
subjective.
• Secondly, the survey forms were provided through medical
representative and filled forms were also collected by the medical
representatives; hence the bias towards product benefits can-not be
ruled out.

21. Conclusion
• Hypertension is a common disease in Indian population. Elevated
sympathetic hyperactivity can lead to various complications in
hypertensive patients. Cilnidipine because of its unique mechanism
of action i.e. L/N calcium channel blockage offers multiple benefits
in hypertensive patients. Because of less pedal edema, reduced
reflex tachycardia and reno-protections cilnidipine may be preferred
over amlodipine.

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