Final Dissertation Report For The Project Entitled PDF

FINAL DISSERTATION REPORT FOR THE PROJECT ENTITLED
“MARKETING SURVEY OF ANTIHYPERTENSIVE DRUGS”
Submitted for partial fulfilment of award of

BACHELOR OF PHARMACY
BY
YASH VARDHAN SHARMA
{Enrolment No. 1512102018}
Under the supervision of

Mr. PRASHANT DHAKKAD
DEPARTMENT OF PHARMACY
SCHOOL OF MEDICAL AND ALLIED SCIENCES
GALGOTIAS UNIVERSITY
GREATER NOIDA, UP
2019
Marketing Research of Antihypertensive Drugs
CERTIFICATE
This is to certify that the project work entitled "MARKETING RESEARCH ON

ANTIHYPERTENSIVE DRUGS" is a bonafide research work done by YASH VARDHAN
SHARMA at Department of Pharmacy, School of Medical & Allied Sciences Galgotias
University, under the supervision and Guidance of Dr. Prashant Dhakkad, Asst. Professor,
School of Medical & Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh.
The work is completed and ready for evaluation in partial fulfilment for the award of Bachelor
of Pharmacy under the Galgotias University, Greater Noida, during the Academic Year 2015-
2016. The matter embodied in it is original and the same has not previously other University
or Institution.
Date: Forwarded by:

Place: Prof. Pramod Kumar Sharma
Dean
School of Medical & Allied Sciences
Galgotias University, Greater Noida
Department of Pharmacy, School of Medical &Allied Sciences, Galgotias University, Gr. Noida
CERTIFICATE
This is to certify that this project entitled “MARKETING RESEARCH ON

ANTIHYPERTENSIVE DRUGS" by YASH VARDHAN SHARMA for the award of
"BACHELOR OF PHARMACY" degree, comprises of the bonafide work done by him in
the Department of Pharmacy, School of Medical & Allied Sciences, Galgotias University,
Greater Noida (UP). Under my Guidance and Supervision and to my full Satisfaction.
Date: Mr. Prashant Dhakkad

Place: Assistant Professor
Department of Pharmacy
School of Medical & Allied Sciences
Galgotias University
Greater Noida (U.P)
ACKNOWLEDGEMENT
It gives me immense gratification to place on records my profound gratitude and sincere

appreciation to each and every one who has helped me in this endeavour.
I gratefully acknowledge, Prof. (Dr.) Pramod Kumar Sharma, Dean, School of Medical
and Allied Sciences, Galgotias University, Uttar Pradesh for his advice, supervision and
crucial contribution, which made him a backbone of this research and so this thesis.
I wish to express my gratefulness to Dr. Prashant Dhakkad, Assistant Professor, Galgotias
University, Greater Noida, for his constant guidance dealing the project.
I wish to express my gratitude to my colleagues and friends for constant encouragement and
support.
Lastly, I have absolutely no words to express my feeling of gratitude to the staff members of
marking executive and sales representatives for their full co-operation and valuable suggestion
in the completion of my project work
At last but not the least, I would like to thanks god for giving, me patience and power for the
successful completion of the project.
YASH VARDHAN SHARMA

B. Pharm VIII Sem.
Enrol. No. 1512102018
Galgotias University, Greater Noida
CONTENTS
Chapter Description Page no.

no.
1.0 Abstract & Introduction 1-3
1.1 Choice of Initial Medication 4-5
1.2 Patient Factor Affecting Antihypertensive Drug Choice 5-6
1.3 Background 6
1.4 Method 6
1.5 Results 6
1.6 Conclusion 6-7
2.0 Study Population 7-8
2.1 Prescription Patterns of New Case of Hypertension 8
2.2 Statistical analysis 8
2.3 Result 9
3.0 Antihypertensive Prescriptions Among Newly-diagnosed Patients 9-11
3.1 Mono-Therapies for New Cases of Uncompleted Hypertension 11
3.2 Daily Drug Cost for Different Antihypertensive Mono- Therapies 11
3.3 Factors associated with initial ARB mono-therapy prescriptions 12
3.4 Discussion 12
3.5 Conclusion 12-13
4.0 Hypertension Improvement Project 13
4.1 Enrollment and Randomization 13-14
4.2 Interventions 14
4.2.1 Measurement 14
4.2.2 Physician Measurement 14
4.2.3 Patient Measurement 15
4.2.4 Outcomes 15
4.2.5 Power and Statistical Analysis 15-16
5.0 Study Design 16
5.1 Study population 16-17
5.2 Outcomes 17
5.3 Explanatory Variables 17
5.4 Statistical Analysis 17
6.0 Results 18
7.0 Conclusion 19-20
8.0 References 21-22
Antihypertensive Drugs
Abstract
Blood pressure reduction is associated with significant reduction in adverse cardiovascular outcomes. Certain
blood pressure lowering drugs have adverse effects on glucose homeostasis, and have been associated with
the development of both pre-diabetes and diabetes during use. There is controversy over the significance of
diabetes that develops during treatment with antihypertensives and whether the benefits of blood pressure
reduction offset the hazards of dysglycemia that can lead to diabetes. Many hypertension treatment guidelines
have recently undergone revisions to include consideration for the metabolic effects of antihypertensive drugs,
particularly in high risk populations. This review summarizes the data related to the benefits of blood pressure
reduction as well as the adverse metabolic effects and new onset diabetes associated with some
antihypertensive medications.
Keywords: Hypertension, Diabetes, Pre-Diabetes, Thiazide Diuretics, ß blockes, New Onset, Diabetes,
Cardiovascular Outcomes
INTRODUCTION
Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure).
Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and
myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the
risk of stroke by 34% of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure,
and mortality from cardiovascular disease. There are many lasses of antihypertensives which lower blood
pressure by different means. Among the most important and most widely used drugs are thiazide diuretics,
calcium channel blockers, ACE inhibitors, angiotensin receptor antagonists (ARBs), and beta blockers.
Which type of medication to use initially for hypertension has been the subject of several large studies and
resulting national guidelines. The fundamental goal of treatment should be the prevention of the important
endpoints of hypertension, such as heart attack, stroke and heart failure. Patient age, associated clinical
conditions and end-organ damage also play a part in determining dosage and type of medication administered.
The several classes of antihypertensives differ in side effect profiles, ability to prevent endpoints, and cost.
The choice of more expensive agents, where cheaper ones would be equally effective, may have negative
impacts on national healthcare budgets. As of 2009, the best available evidence favours the thiazide diuretics
as the first-line treatment of choice for high blood pressure when drugs are necessary. Although clinical
evidence shows calcium channel blockers and thiazide-type diuretics are preferred first-line treatments for
most people (from both efficacy and cost points of view). an ACE inhibitor is recommended by NICE in the
UK for those under 55 years old.
Diuretics help the kidneys eliminate excess salt and water from the body's tissues and blood.
• Loop diuretics:
▪ Bumetanide
▪ Ethacrynic acid
▪ Furosemide
▪ Torsemide
• Thiazide diuretics:
▪ Epitizide
▪ Hydrochlorothiazide and chlorothiazide
▪ Bendroflumethiazide
• Thiazide-like diuretics:
▪ Indapamide
▪ Chlorthalidone
▪ Metolazone
• Potassium-sparing diuretics:
▪ Amiloride
▪ Triamterene
▪ Spironolactone
Calcium channel blockers block the entry of calcium into muscle cells in artery walls.
• Dihydropyridines:
▪ Amlodipine
▪ Cilnidipine
▪ Felodipine
▪ Isradipine
▪ Lercanidipine
▪ Levamlodipine
▪ Nicardipine
▪ Nifedipine
▪ Nimodipine
▪ Nitrendipine
• Non-dihydropyridines:
▪ Diltiazem
Verapamil ACE inhibitors inhibit the activity of angiotensin-converting enzyme (ACE), an enzyme
responsible for the Conversion n of angiotensin I into angiotensin II, a potent vasoconstrictor.
• Captopril
• Enalapril
• Fosinopril
• Lisinopril
• Perindopril
• Quinapril
• Ramipril
• Trandolapril
• Benazepril
1.1. Choice of Initial Medication
For mild blood pressure elevation, consensus guidelines call for medically supervised lifestyle changes and
observation before recommending initiation of drug therapy. However, according to the American
Hypertension Association, evidence of sustained damage to the body may be present even prior to observed
elevation of blood pressure. Therefore, the use of hypertensive medications may be started in individuals with
apparent normal blood pressures but who show evidence of hypertension related nephropathy, proteinuria,
atherosclerotic vascular disease, as well as other evidence of hypertension related organ damage.
If lifestyle changes are ineffective, then drug therapy is initiated, often requiring more than one agent to
effectively lower hypertension. Which type of many medications should be used initially for hypertension has
been the subject of several large studies and various national guidelines. Considerations include factors such
as age, race, and other medical conditions. In the United States, JNC8 (2014) recommends any drug from one
of the four following classes to be a good choice as either initial therapy or as an add-on treatment: thiazide-
type diuretics, calcium channel blockers, ACE inhibitors, or angiotensin II receptor antagonists.
The largest study, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
in 2002. concluded that thiazide-type diuretics are better and cheaper than other major classes of drugs at
preventing cardiovascular disease, and should be preferred as the starting drug. ALLHAT used the thiazide
diuretic chlorthalidone. (ALLHAT showed that doxazosin, an alpha-adrenergic receptor blocker, had a higher
incidence of heart failure events, and the doxazosin arm of the study was stopped.)
A Subsequent smaller study (ANBP2) did not show the slight advantages in thiazide diuretic outcomes
observed in the ALLHAT study, and actually showed slightly better outcomes for ACE-inhibitors in older
white male patients.
Thiazide diuretics are effective, recommended as the best first-line drug for hypertension by many experts,
and are much more affordable than other therapies, yet they are not prescribed as often as some newer drugs.
Hydrochlorothiazide is perhaps the safest and most inexpensive agent commonly used in this class and is very
frequently combined with other agents in a single pill. Doses in excess of 25 milligrams per day of this agent
incur an unacceptable risk of lower potassium or hypokalaemia. Patient with an exaggerated hypokalemic
response to a low dose of thiazide diuretic should be suspected to have hyperaldosteronism, a common cause
of secondary hypertension.
Other drugs have role treating hypertension. Adverse effects of thiazide diuretics include
hypercholesterolemia, and impaired glucose tolerance with increased risk of developing Diabetes mellitus
type 2. The thiazide diuretics also deplete circulating potassium unless combined with a potassium-sparing
diuretic or supplemental potassium. Some authors have challenged thiazides as first line treatment. However,
as the Merck Manual of Geriatrics notes, "thiazide-type diuretics are especially safe and effective in the
elderly.
Current UK Guidelines suggest starting patients over the age of 55 years and all those of African/Afro
Caribbean ethnicity firstly on calcium channel blockers or thiazide diuretics, whilst younger patients of other
ethnic groups should be started on ACE-inhibitors. Subsequently if dual therapy is required to use ACE-
inhibitor in combination with either a calcium channel blocker or a (thiazide) diuretic. Triple therapy is then
of all three groups and should the need arise then to add in a fourth agent, to consider either a further diuretic
(e.g. spironolactone or furosemide), an alph.
1.2. Patient Factors Affecting Antihypertensive Drug Choice
The choice between the drugs is to a large degree determined by the characteristics of the patient being
prescribed for, the drugs' side-effects, and cost. Most drugs have other uses; sometimes the presence of other
symptoms can warrant the use of one particular antihypertensive. Examples include:
• Age can affect choice of medications. Current UK guidelines suggest starting patients over the age of
55 years first on calcium channel blockers or thiazide diuretics.
• Anxiety may be improved with t the use of beta blockers.
• Asthmatics have been reported to have worsening symptoms when using beta blockers.
• Benign prostatic hyperplasia may be improved with the use of an alpha blocker.
• Chronic kidney disease. ACE inhibitors or ARBs should be included in the treatment plan to improve
kidney outcomes regardless of race or diabetic status.
• Diabetes. The ace inhibitors and angiotensin receptor blockers have been shown to prevent the renal
and retinal complications of diabetes mellitus.
• Gout may be worsened by diuretics, while losartan reduces serum urate.
• Kidney stones may be improved with the use of thiazide-t pe diuretics.
• Heart block. Beta blockers and nondihydropyridine calcium channel blockers should not be used in
patients with heart block greater than first degree. JNC8 does not recommend beta blockers as initial
therapy for hypertension.
• Heart failure may be worsened with nondihydropyridine calcium channel blockers, the alpha blocker
doxazosin, and the alpha-2 agonists moxonidine a and clonidine. Whereas Beta blockers, diuretics,
ACE inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists have been shown
to improve outcome.
• Pregnancy. Although a-methyldopa is generally regarded as a first-line agent, labetalol and metoprolol
are also acceptable. Atenolol has been associated with intrauterine growth retardation, as well as
decreased placental growth and weight when prescribed during pregnancy. Ace inhibitors and
angiotensin Ⅱ receptor blockers (ARBs) are contraindicated in women who are or who intend to
become pregnant.
• Race. JNC8 guidelines particularly points out that when used as monotherapy, thiazide diuretics and
calcium channel blockers have been found to be more effective for reducing blood pressure in black
hypertensives than B-blockers, ACE inhibitors, or ARBs.
• Tremor may warrant the use of beta blockers.
The JNC8 guidelines indicate reasons to choose drug over for certain individual patient.
1.3 Background
Knowledge of existing prescription patterns the treatment of newly-diagnosed hypertension can provide useful
information for improving c clinical practice in this field. The aims of this study are to determine the
prescription pattern and time trends for antihypertensive medication in newly-diagnosed cases of
uncomplicated hypertension in Taiwan and to compare these with current clinical guidelines.
1.4. Methods
A total of 6,536 newly-diagnosed patients with uncomplicated hypertension, aged ≥30 years, were identified
from m the representative 200,000-person sample in the computerized reimbursement database of the National
Health Insurance in Taiwan. These patients were followed from 1998 to 2004 with all diagnoses, prescription
data and medication charges being retrieved for subsequent analysis.
1.5. Results
Prescription patterns varied by age, gender and clinical facilities, with mono-therapies being found to be
dominant in the first year, albeit declining over time. Calcium channel blockers and beta-blockers were the
most frequently prescribed antihypertensive drugs, either alone or in combinations. Although least expensive,
the prescription rates of diuretics were low, at 8.3% for mono-therapies and 19.9% overall. The prescription
rate for angiotensin receptor blockers (ARBs) was elevated considerably over time. After controlling for other
related factors by multiple logistic regression analysis, ARBs were found to be prescribed mainly by medical
centres or regional hospitals.
1.6. Conclusion
These findings indicate the existence of a gap between current clinical practice and the desired goal of cost-
effectiveness in Background
Hypertension, a leading contributor to the global burden of causes of disease, continues its upward growth
trend. Poor control of this highly prevalent disease can lead to the development of ischemic heart disease,
heart failure, stroke and chronic renal insufficiency. Along with its comorbidities, hypertensive related
conditions have accounted for almost a third of the total causes of death in Taiwan in recent years [8); in 2003
the total pharmaceutical expenditure on antihypertensive medication was USSO.32 billion, accounting for
approximately 27% of the overall annual outpatient pharmaceutical expenditure on western-style medicines.
As a result of various clinical trials and studies, a range of clinical trials studies guidelines on antihypertensive
treatment been published over the past decade.
Based on clinical defence and cost-effectiveness guidelines developed by the Joint National Committee (JNC)
in the United States and the National Institute for Health and Clinical Excellence (NICE) in the United
Kingdom recommended that diuretics (particularly thiazide-type diuretics) should be the drug of first choice
for patients with no compelling indications. However, the results of various studies have shown that adherence
to such clinical guidelines and recommendations are not at all uniform: indeed, they have been found to vary
by time period and country, and by the characteristics of patients and physicians.
Taiwan's National Health Insurance (NIH) has not yet established a definite guideline for antihypertensive
drug therapy. Given the enormous growth in healthcare expenditure within the NHI (rom USS13.9 billion in
1997 to US$20.5 billion in 2005) [24] and the limited resources for healthcare, there is a clear need to explore
physician practices, including prescription trends, in antihypertensive and other therapies.
The computerized reimbursement database of the NHⅠ in Taiwan provides us with a valuable opportunity to
assess the real practice patterns of antihypertensive pharmaceutical therapies. The NHI program, which is a
mandatory nationwide health insurance system, implemented in Taiwan in March 1995. Overall coverage
continues to rise, from 96.2% in 2000 to 98.3% in 2006, and almost the entire population of Taiwan is now
covered by the system. Furthermore, in contrast to the NHI systems of many Western nations, patients in
Taiwan are free to choose care providers in a competitive healthcare market.
2.0 Study Population
This study uses a 200,000-person representative random sample from the computerized reimbursement
database of the NHI, between January 1997 and December 2004, Details on the gender and date of birth of
the patients, the date of prescription. commercial names of drugs, drug dosages/duration and costs for each
prescription are recorded in the reimbursement files.
Patients initially identified were newly-diagnosed with essential hypertension on at least three occasions, were
being treated for this condition, and had received their first antihypertensive medication between 1 January
1998 and 31 December 2004. In order to verify that a case was a new one, a period of at least one year was
required (January to December of 1997) without any treatment and/or diagnosis relating to hypertension.
To prevent potential confounding by comorbidities in the prescription patterns of antihypertensive agents at

different clinical facilities, patients diagnosed with suspected diabetes mellitus, ischemic heart disease,
diseases of pulmonary circulation, other forms of heart diseases (including dysrhythmia and heart failure),
stroke or renal diseases were excluded from the sample. In order to ensure adherence to these criteria, any of
the above diagnoses may not have appeared in any hospitalization file prior to the patient having been
diagnosed as hypertensive, and the diagnoses may not have appeared more than three times in ambulatory
outpatient files. We discarded those diagnoses appeared only once or twice in ambulatory outpatient files to
exclude suspected or uncertain cases where claims were filed to allow for further diagnostic examination.
2.1 Prescription Pattern of new Cases of Hypertension
All antihypertensive drug prescription records from ambulatory care claims and prescriptions dispensed at
contracted pharmacies were retrieved and analysed for our sample of newly diagnosed patients aged 30 years.
Patients were stratified by gender and age, with age being split into two sub-groups: the younger group (30-
54 years of age) and the older group (≥55 years). The clinical facilities were classified into four types, medical
centre, regional hospitals, local hospitals and primary care clinics, based upon the level of medical care
provided and the size of the institution as recognized by the NHⅠ.
Antihypertensive drugs were categorized according to the 199 World Health Organization-International
Society Hypertension Guidelines for the Management of Hypertension (WHOISH, 1999) and the Seventh
Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood
Pressure. Six major categories of antihypertensive drugs generally are available, including angiotensin-
converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium channel
blockers (CCBs), diuretics, and others (all other antihypertensive classes including alpha-blockers.
Prescriptions for a chronic disease in Taiwan, such as hypertension, most frequently involved the prescribing
of drugs for 28- to 90-day periods, which would allow the patient visit a doctor every one to three months.
Since each prescription may have contained different combinations of drugs and durations of medication,
analysis of the data was undertaken using the prescription rate as calculated as the number of prescriptions
containing a specific antihypertensive agent divided by the total number of prescriptions. A comparison of the
prescription time was undertaken for each year, beginning with the first antihypertensive prescription. Daily
drug costs, excluding all pharmacy service fees or other peripheral costs, were also calculated for each
prescription. The drug costs are set by the Bureau of NHI and universally applied to clinical facilities
regardless of their sizes.
2.2. Statistical analysis
After being weighted by duration of medication, daily drug costs are expressed as time-weighted means, while
other results are expressed as means standard deviation (SD). The Chi-square test was carried out to determine
the statistical significance of the differences between the prescription rates, with the Cochran-Armitage test
also performed to assess the linear time trends over the sample period from the time of the initial treatment.
Means of daily drug costs were compared using the Student t-test. Finally, multiple logistic regression analysis
was performed to identify possible influential factors as a result of the prescribing of a single class of
antihypertensive medication as a mono-therapy. SAS version 9.1 for Windows was used for the analysis of
all of the data in this study. All tests were two-sided, and a p-value of <0.05 was considered statistically
significant. Whenever multiple comparisons were performed Bonferroni adjustment were made accordingly.
2.3. Results
The dataset contained a total of 15,835 patients over the age of 30 years who had received their initial dose of
antihypertensive drugs for essential hypertension between 1 January 1998 and 31 December 2004. Of this
total, 9,299 were excluded on the basis that one or more earlier morbidities had been recorded. We were
therefore left with a total of 6,536 patients and 178,754 prescriptions for antihypertensive agents for
subsequent analysis.
Of the total sample of 6,536 patients, 3,268 (50.0%) were women and 49.3% were 255 years old, with a mean
of 55.9 and SD of 12.3 years. The mean follow-up duration after the first prescription of antihypertensive
medication was 42.8± 27.2 months, while the average number of overall prescriptions was 27.3± 26.0. Each
prescription included 1.64± 0.84 antihypertensive drugs prescribed for an average period of 22.3 ± 10.5 days.
The mean number of actual medical visits over the entire period of study was 25.1+24.5.
3.0. Antihypertensive Prescriptions Among Newly-diagnosed Patients
Over half of the prescriptions for newly-diagnosed cases of uncomplicated hypertension involved single
antihypertensive drug therapy (n - 94,797; 53.0%), with women and older patients receiving more mono-
therapies. Medical centres and regional hospitals prescribed more combination therapies, as compared with
primary care clinics (Table 1). The percentage of mono-therapy treatments declined over time from the initial
diagnosis, whereas there was a gradual increase in the percentage of combination therapies (Figure 1). The 10
most frequently prescribed antihypertensive regimens, ranked in order of prescribing frequency were as
follows s: CCBs (17.7%), beta blockers (14.5%), ACEIs (8.2%), CCBs + beta blocker (7.7%), other (5.3%),
diuretics (4.4%), CCBs + ACEls (4.0%), ARBs (3.0%), CCBs ARBs (2.6%), beta-block + diuretics (2.4%).
Figure 1
Prescription pattern time rends for combinations of mono, two-, three- and four (+)-drug treatment therapies.
Note: *Indicates p-value <0.0125 under the Cochran-Armitage trend test, being significant with Bonferroni
adjustment for multiple comparisons (p< 0.05/4=0.0125)
Table 1
Prescription patterns of antihypertensive therapies for newly-diagnosed uncomplicated hypertension patients,

1998-2004
*Total sample number = 6536 patients.
*No. refers to the number of prescriptions under each treatment regimen; % refers to the percentage of the
total drugs prescribed under the four treatment regimens.
*As a result of missing data, the sum of the total number of prescriptions over the four types of clinical
facilities is smaller than the overall number of prescriptions.
*Pairwise group comparisons are performed taking primary care clinics as the reference.
*Significant p-value with the Bonferroni-adjusted a-level, p < 0.0025
A summary of the total number of prescriptions for the different categories of antihypertensive drugs is
provided in Table2, where it is shown that the most frequently prescribed antihypertensive agents were CCBs
(n=92,574; 51.8%), with beta-blockers as the second most frequently prescribed, followed by ACE inhibitors,
diuretics, others and ARBs.
Table 2
Distribution of antihypertensive drugs for newly-diagnosed uncomplicated hypertension patients, by gender,

age and clinical facility, 1998-2004
*Total sample number - 6536 patients.
*No. refers to the number of prescriptions for each class of drug, % refers to percentage of the total prescription
for six classes of drugs. As a result of missing data, the sum of the total prescriptions over the four types of
clinical facilities is smaller than the overall number of prescriptions. The sum of the prescriptions rates for all
six classes of drugs exceeds 100% because the average prescription contained more than one drug.
*CCBs = calcium channel blocker; ACE = angiotensin-converting enzyme; ARBs = angiotensin receptor
blockers. The prescription rate for ARBs, which was the highest in medical centres (22.6%), was almost five
times the rate for primary care clinics, and was also higher than the prescription rate for ACE inhibitor and
diuretics. There was an increase with time in the number of prescriptions for ARBs, CCBs and diuretics. There
was an increase with time in the number of prescriptions for ARBs, CCBs and diuretics, whereas the number
of prescriptions for ACE inhibitors remained stable.
Prescription distribution time trends for antihypertensive agents. Note: *indicates p-value <0.0083 under the
ran-Armitage trend test, being significant with Bonferroni adjustment for multiple comparisons (p < 0.05/6=
0.0083).
3.1. Mono- therapies for New Cases of Uncomplicated Hypertension
Among all of the mono therapy prescriptions, the most frequently prescribed antihypertensive agent were
CCBs (n= 3171; 3.5%) and beta blockers (n=25,835; 27.3%). Older patients (aged over 55 years) were treated
with CCBs more often than younger patients, with beta-blockers being more frequently prescribed.
The prescription rates for beta- blockers were higher among women and younger patients(p<0.0001), while
the prescription rates of diuretics were higher among women and older patients (p 0.0001). In contrast, ACE
inhibitors and ARBs were more frequently prescribed for younger patients. Medical centres and regional
hospitals were found to have prescribed ARBs much more often than primary care clinics(p<0.0001), where
the prescribing of ACE inhibitors was found to be much more common (p <0.0001)
3.2. Daily Drug Costs for Different Antihypertensive Mono-Therapies
The daily costs for mono-therapy medication, in order from low to high, are as follows.
Diuretics were the cheapest with a mean of US $0.17, followed by beta-blockers (US $0.27) and others (US
$0.28). The costs for CCBs and ACE inhibitors were almost the same (USS0.56), while the costs for ARBs,
at a daily average of USS0.85, were about five times those of diuretics. With the exception of the class of
'other' drugs, the means of the daily drug costs did not vary significantly by gender, age or clinical facility.
3.3. Factors associated with initial ARB mono-therapy prescriptions
As Table 4 shows, following adjustment by multiple logistic regression analysis, those prescriptions involving
ARBs as an antihypertensive mono-therapy were found to be associated with subsequent diagnoses of diabetes
mellitus (odds ratio (OR)- 1.5: 95% CI:14-1.7), regional hospitals (OR-3.6,.95% CI: 3.3-3.9), medical centres
(OR - 5.8,95% CI:5.3-6.2) and e period after the year 2001 (OR -24 for 2001-2,and45 for 2003-2004).
3.4 Discussion
This is one of the first studies of its kind to undertake an assessment of the national prescription patterns and
time trends in Taiwan for antihypertensive medication for uncomplicated hypertension, we found that whether
in mono-therapies or overall treatment, CCBs were the most commonly prescribed rugs, followed by beta-
blockers. Among all of the mono-therapies, the lowest average daily medication costs were for diuretics, at
less than one third of the cost for CCBs or ACE inhibitor, and about one fifth on the cost for ARBs. The
prescription rate for diuretics was, however, surprisingly low, accounting for only 8.3% mono-therapies, and
indeed the diuretic prescription rate was the second lowest of all, only after ARBs (5.7%). Beginning in 2006-
7, the National Health Research institutes of Taiwan has begun to draft clinical guidelines for various health
conditions, including the treatment of hypertension. However, most physicians schemed to accept the
recommendation of the US JNC or the WHO/ISH guideline during the time of this study. The evidence-based
clinical guidelines for antihypertensive treatment published by both the C in 2003 and the NICE in 2004
contained recommendations for low dosages of thiazide diuretics as the first-line drug for essential
hypertension with no compelling indications Such a recommendation also appeared in the 2003 statement
published by the WHO/ISH, and indeed, diuretics have been found to be the mainly prescribed class of
antihypertensive drugs in the United Kingdom, Denmark and the United States.
Researchers have indicated a substantial potential for cost savings if thiazides are prescribed rather than other
more expensive drugs for treatment of hypertension. Given that the prescription pattern in Taiwan appears to
utilize more non-thiazide medications that are generally more expensive, this issue would be worthy of further
study with the aim of comparing the cost-effectiveness of antihypertensive treatment in Taiwan with those of
other countries. Considerable variation in antihypertensive prescribing patterns exists internationally.
Fretheim and colleagues compared.
3.5 Conclusion
The initial prescription patterns for antihypertensive therapies for uncomplicated hypertension in Taiwan seem
to be inconsistent with the current international clinical guidelines. Although diuretics are the least expensive
class of antihypertensive drugs, they are nevertheless being used as second- or the third-line method of
medication, with a notably low prescription rate. There has been a growing trend in the prescribing of ARBs
as the initial choice of therapy for uncomplicated hypertension, particularly in medical centres and regional
hospitals. The result indicates a need for greater awareness of the evidence-based guidelines for
antihypertensive drug therapy amongst physician and the general public. Given the existence of the national
health insurance amongst system physicians in Taiwan, and the there is still significant room for improvement
in the cost-effectiveness of antihypertensive treatment. We recommend reaching a consensus on this matter
an developing a domestic clinical guideline taking cost-effectiveness into consideration as soon as possible.
4.0. Hypertension Improvement Project (HIP)
The Hypertension Improvement Project (HIP) was approved by the Duke Institutional Review Board. The
design was a nested 2x2 randomized, controlled trial of a physician intervention, a patient intervention, and
both combined, compared with neither. Nesting occurred both at the level of the practice and the level of the
physician. Primary care practices were randomly assigned to the physician intervention (MD-I) or to the
physician control (MD-C) group. All of the participating physicians within a given practice had the same
randomization assignment Within the participating practices, patients were individually randomized to the
patient intervention (Pt-l) or to usual care (Pt-C). Follow-up measurements were performed at 6 and 1-months
post randomization. The primary outcome was systolic BP change at 6 months. The study design is displayed
in
4.1. Enrollment and Randomization
Four matched pairs of community-based primary care practices in central North Carolina were randomized
between 2005 and 2007. Practices were matched with regard to specialty (internal medicine or family practice)
and patient socioeconomic mix. One practice of each pair was blindly assigned by the study statistician to
intervention or control status. Within each practice, all of the physicians were invited to participate, with a
goal of enrolling 4 physicians per clinic. Each physician provided written informed consent. For logical
reasons, we enrolled practices in waves or “cohorts” of 1 intervention and 1contrl clinic each.
We sent a recruitment letter from the physician to potentially eligible patients We sought to enrol 10 to 15
patients from each physician. Patients were eligible if they were ≥25 years old and were hypertensive on the
basis of billing codes. Patients were excluded if they had self-reported chronic kidney disease (CKD), a
cardiovascular disease event within the past 6, or were pregnant, breastfeeding, or planning a pregnancy
Potential study participants were pre-screened by telephone and then attended 2 screening visits at which
eligibility was confirmed, written informed consent was obtained, and baseline data were collected.
Randomization to Pt-C or Pt-I occurred in varying block sizes using a computer-generated algorithm, stratified
by cohort and clinic. Randomization was performed by the study statistician; all of the data collection staff
remained blinded to the participant's treatment assignment. It was not feasible to blind patients or providers
to their own randomization assignment. Patients were asked not to discuss their randomization assignment
with their provider, but strict blinding of the physicians was not feasible.
4.2. Interventions
MD-I lasted 18 months and consisted of 3 elements. First, 2 training modules were provided on-line. The first
module addressed the Seventh Joint National Committee on Prevention, Detection, Evaluation and Treatment
of High Blood Pressure (NC-7) guidelines, and the second addressed lifestyle modification for BP control.
Each module required ≈45 minutes, included a quiz that gave immediate feedback, and provided Continuing
Medical Education credit through Duke University. Participating physicians completed the modules within 2
weeks of randomization and before the patient intervention began. Second, each physician in MD-I received
an evaluation and treatment algorithm that summarized, on a color-coded, pocket-sized laminated card, the
major JNC-7 guidelines, including lifestyle guidelines and a decision tree. Third, a quality improvement (QI)
procedure assessed clinical performance measure data form every time a HIP patient had a clinic visit.
4.2.1 Measurements
Measurements were obtained from all of the randomized physicians and all of the randomized patients at
baseline and 6 and 18 months.
4.2.2 Physician Measurements
All of the physicians, regardless of treatment assignment, were asked to complete a self-administered
questionnaire concerning demographics, education, training, characteristics of patients under their care, and
usual practice patterns.
4.2.3 Patient Measurements
All of the study measurements were obtained during face-to face clinic visits by trained, certified study
personnel who were blinded to intervention assignment. For BP measurement, personnel were trained and
certified using methods used in previous BP trials. Duplicate measurements were obtained with a calibrated
automated appropriate-sized cuff after the participant had been seated quietly for 5 minutes. At each time point
(baseline and 6 and 18 months), participants attended 2 study visits 1 week apart. BP for that time point was
defined as the mean over the 2 study visits (i.e., 4 BP readings). For eligibility, hypertension was considered
present on the basis of billing codes. For all other purposes, hypertension was defined as measured systolic
(S)BP140 mm Hg, diastolic (D)BP90 mm Hg, or taking antihypertensive medication. BP treatment goals were
defined on the basis of JNC-7 guidelines.
Height was measured once to the nearest 0.1 cm, using a calibrated, wall-mounted stadiometer. Weight was
measured in duplicate with the participant wearing light, indoor clothes without shoes and using a high-quality,
calibrated digital scale. Body mass index was calculated as the Quetelet Index (Kilograms per meter squared).
Dietary intake was assessed with the Block Food Frequency Questionnaire.
Physical activity was assessed by a calibrated, triaxial accelerometer (RT3, stay healthy, Inc) worn for ≥10
hours per day for ≥4 days over the course of a week, including 1 weekend day.
4.2.4 Outcomes
The primary outcome was change in SBP from baseline to 6 months. Secondary outcomes included change in
DBP at 6 months, BP change at 18 months, the effect of treatment on weight loss, dietary pattern, physical
activity, fasting blood glucose and lipids, and the proportion of patients with adequate BP control.
4.2.5 Power and Statistical Analysis
The original study design defined the primary outcome as the proportion at goal BP, and, with a planned
sample size of 500 patients, was powered to detect an effect size of 0.3. During the study it became clear that
the proportion of patients who were at goal BP at baseline (assessed blinded to treatment group) was higher
than anticipated on the basis of national statistics, potentially inducing a ceiling effect that could have left the
study underpowered. Consequently, with the permission of the trial's data and safety monitoring board, the
primary outcome was changed to the continuous variable, change in SBP, with change in proportion at goal
relegated to a secondary outcome. In addition, recruitment for the remaining study participants targeted those
with BP above goal at baseline. The achieved sample size of 574 patients in 8 practices provided 80% power
to detect a difference of 4 mm Hg. Comparisons across treatment groups were adjusted for baseline value and
cohort. Identifying the specific drug-class BP response markers tackles two main methodological issues,
namely the high in-individual variability of BP, and the multiplicity of the biomarkers and of their nature (for
example, demographic, biological, environmental, behavioural and genetic). This variability is independent
of drug response. Physicians and patients do not fully understand it and it is not properly integrated into the
management of hypertension., These large random variations may be a source of disappoint for both
physicians and patients desperately hoping to control BP, leading to poorly justified treatment withdrawal or
treatment changes. We set up the identification of the Determinants of the efficacy of Arterial blood pressure
Lowering drugs (IDEAL) Trial with the specific aim of identifying factors that are associated with different
BP responses to two drugs. The trial's methods (including experimental design and statistical analysis) were
designed to minimize the consequences of BP variability on the expected results and take the various origins
of BP differential responses to drug into account.
This article explores baseline simple phenotype individual characteristics as marker of BP response to
indapamide de and perindopril. These two drugs were chosen because they represent two classes with the best
level of evidence for the reduction of cardiovascular risk.
5.0 Study design
The study was conducted according to the Declaration of Helsinki ethical Principles for Medical research
involving Human Subjects and was founded by public grants from the 2003 hospital program from Clinical
Research (French Ministry of Health) and the French Society of Hypertension. The study Protocol was
approved by an institutional ethical review board and the French Data Protection Agency in November 2004
All patients gave signed informed consent before inclusion. Study drugs were donated by SERVIER France
(Suresnes, France). The company did not participate in study design, study conduct, data collection, statistical
analysis, interpretation o of results or manuscript preparation.
The complete study design is described elsewhere. The protocol was registered on ClinicalTrials.gov
NCTOO128518. The IDEAL Trial was a multicentre, randomized, cross-over, double-blind double-placebo-
controlled clinical trial that evaluated BP response to perindopril 8 mg and indapamide 1.5 mg slow release.
Eligible subjects were included at the selection visit. After inclusion all patients went through a 2-week single-
blind double-placebo run-in phase in order to assess potential treatment compliance. They were further
randomized to one of the four sequences, each of them including four 4-week periods: two active treatment
periods, separated by placebo wash-out periods. Total study duration for each patient was approximately 22
weeks. Randomization was centralized. Perindopril doses were increased from 4 mg (tert-butylamine salt
equivalent to 5 mg arginine salt) to 8 mg after 1-week. Indapamide 1.5 mg slow release doses were
administered each morning over a period of 4 weeks. Placebo tablets were indistinguishable from the active
treatment. Urine indapamide and serum N-acetyl-Ser-Asp-Lys-Pro dosages re performed systematically to
check for patient compliance at the end of each of the four follow-up periods.
5.1 Study population
Patients were recruited at eight participating centres in France. Included patients were aged 25-70 years, with
no antihypertensive treatment in past 6 months, a mean (average of the last four measurements) BP≥140 mm
Hg and <180mm Hg for diastolic at inclusion visit. Exclusion Criteria were renal insufficiency or high
cardiovascular risk because of a previous history of vascular disease or uncontrolled or insulin- requiring
diabetes, secondary hypertension, an intolerance to ambulatory-BP monitoring or a brachial perimeter of >33
cm, potentially increased BP variability, a treatment that could interfere with BP, pregnant women of
childbearing age planning to get pregnant.
5.2 Outcomes
The main outcome was office systolic BP (SBP) measured during randomization and at all four follow up
visits in a standardized manner. Seven measurements were taken in the supine position every 5min, on the
dominant arm (determined at the inclusion visit). The same automatic device was used for each patient
throughout his or her participation in the study. All seven BP measurements were used in the statistical
analysis.
5.3. Explanatory variables
The baseline explanatory variables analysed in this report include age (years). gender (female as reference),
body mass index (kg m alcohol consumption (number of glasses per day), smoking (current, former and non-
smoker) echocardiography left ventricular hypertrophy (yes/no), duration of hypertension (years, diabetes
(yes/no), family history of hypertension (yes/no) and serum creatinine levels.
5.4. Statistical analysis
The inclusion of 400 participants (based on a wo-sided alpha risk of 5% with 90opower) would have made
the trial powerful enough to detect a difference of 2 mm Hg for SBP between two groups of patients of similar
size. We received two grants, but the financial support was less than expected, allowing us to recruitment
theoretically 200 patients. We stopped recruiting patients before the intend sample size was reached because
recruitment was slower than expected and the research grant expired. Hospices Civils de Lyon, the institutional
sponsor, decided to stop patient recruitment in June 2009. This decision was only based on administrative
grounds, without knowledge of the data.
SBP measurements at baseline und during follow-up were modelled using a linear mixed- effect model. The
random part modelled the deviation between the patient’s specific mean and the overall mean given the factors
included in the fixed part of the model, and hence modelled the variation from patient to patient not explained
by the fixed part of the model. The random part included a random SBP mean by patient during the placebo
period, and random deviation to this mean during the perindopril and indapamide period, and random
deviations to this mean during the perindopril and indapamide periods as well as the correlations between
these random effects. The interactions between variable were also introduced in the multivariate model, as
well as the third-order interaction between age, gender and variable. The final model was obtained using
backward selection procedure with a significance level of 0.05.
6.0 Results
Study population
In the IDEAL Trial, 139 patients were included between Murch 2005 and May 2010. One hundred twenty-
four patients were randomized and 115 of them completed all four periods. The main reason for withdrawal
between the inclusion visit and randomization was consent withdrawal (9 out of 15 patients) and I patient for
an adverse event during one of the placebo run-in phases. Six patients experienced serious adverse events after
randomization: one was hospitalized for a pulmonary infection with hyponatremia, one had hypokalaemia,
one had a being cutaneous allergic reaction from indapamide, one suffered chest pain with a surge in
hypertension (this was the only case in these six patients who did not stop the study treatment and contributed
to the final analysis), one had an ankle sprain and one died suddenly. This death occurred in a 55year-old man
without any known risk factors (body mass index 22 kg m, non-smoker, normal echocardiogram without left
ventricular hypertrophy) expect hypercholesterolemia, with a family history at inclusion), with a family
history of hypertension and moderate BP levels measured within 24 hr. Ambulatory-BP monitoring was
135/80 mm Hg. He was found dead after the third follow-up visit, a few hours after beginning the last treatment
period.
One patient was excluded from analysis because of lack of adherence. Two other patients were excluded
because of incoherent data on compliance. The final analysis was based on 112 patients that completed all
four periods and had complete and coherent data.
Response to drug and other determinants of BP
Observed mean placebo-adjusted BP reductions under indapamide and perindopril in the 112 patients
considered for the final analysis were of similar magnitude: -7.2 (sd. 9.8)/-4.0 (sd. 6.2) mm Hg and-6.6 (sd.
11.0y-4.2 (sd. 6.7) mm Hg, without significant difference.
In univariate analyses, male sex, body mass index and both treatments were significant predictors of SBP (P
0.003,0.002, <0.0001 and <0.0001, respectively). The carry-over effects of treatments were nonsignificant
(P=0.49). study visits and study centres were significantly associated with SBP (P<0.0001 and 0.02,
respectively). Alcohol consumption and left ventricular hypertrophy were weak predictors of SPB (P-values-
<0.20). Using estimates from the multivariate model, the response to indapamide was a decrease in 29 of the
37 women (78%), with a decrease of up to 10 mm Hg and more for 22/37 (59%) of them. Twenty-two men
(29%) had an increase in SBP and 26/75 (35%) had a 10 mm Hg or more decrease while taking indapamide.
In all, 28/37 (76%) women had a decreased SBP and for 17/37 (46%) this decrease was of 10 mm Hg or more
while taking perindopril. Twenty-four men (32%) had an increased SBP and 22/75 (29%) had a >10mm Hg
decrease on perindopril.
7.0 Conclusion
IDEAL Trial methodology (experimental design and statistical analysis) was specifically set up to explore
individual markers of Br response to drugs. The design was defined to neutralize the impact of placebo effect
and to minimize the effect of regression to the mean. The placebo effect was controlled by having placebo
periods between active periods. Regression to the mean was reduced by keeping patients whose BP did not
reach the required level at randomization in the study population. All seven BP measurements taken during
follow-up were included in a mixed-effects regression model.
The IDEAL Trial has successful achieved this objective and confirms that response markers do exist and can
be identified, even n in size-limited trials. In this study population, 19% of SBP response changes were from
indapamide and 24% from perindopril. Several placebo-controlled trails with the same objective were
performed in the past. In the US Department of Veteran Affairs parallel-group trail on 1292 men, being
African American was better response maker to calcium antagonist than to drugs acting on the renin-
angiotensin system (angiotensin-converting enzyme (ACE) inhibitors, angiotensin 2 antagonist inhibitor and
beta blocker). In the same study aging was response maker to diuretics. Two cross-over trials explored
correlations between BP response to drugs. In the first trial, 72 patients received a beta-blocker (B), an ACE
inhibitor (A) and a calcium antagonist (C). In the second trial,56 patients received these three drug classes
plus a diuretic(D). Plasma renin level, which decrease on average with age, were associated with a response
to the beta blocker in the first trial. The second trial led to the Cambridge AB/CD rule for optimization of
antihypertensive treatment because there was a significant correlation between the responses to A and B on
the one hand and C and D on the other hand, without any other significant correlations This suggests that renin
levels and their variation with age could be the main determinants of class-specific responses. The more recent
ROTATE Trial with 97 patients tested the four previous drug classes plus an angiotensin 2 antagonist. The
authors concluded that phenotype (such as ethnic origin), environmental (such as sodium consumption) and
genetic (ADDI 614G-T polymorphism) biomarkers were significantly associated with drug response. The
GENRES trial included 208 men and evaluated the same drug classes except for ACE inhibitors. Its authors
concluded that age and initial BP were associated with BP response confirming the correlations observed
previously with plasma renin levels. It failed to confirm the correlation of response to beta-blockers with beta-
adrenergic receptor polymorphisms.
With a full-analysis population of 12 patients displaying an average placebo-controlled BP response of -7.2/-

4.0 mm Hg on indapamide and -6.6/-4.2 mm Hg on perindopril, the IDEAL Trial allowed us to confirm the
role of two important markers for SBP response to drugs. This average placebo-adjusted BP reduction is about
25% less than that expected from the average estimate of a standard dose of an antihypertensive drug,
estimated at around 9mm Hg from a systematic review of 354 trials by Law et al. This may be explained by
the short-term exposure to treatment and the make-up of the study population because there were relatively
less responders than in other trials. In the same paper, Law et al. observed an association between pre-
treatment BP and BP response without separating drug classes. We noticed this for indapamides, but not
perindopril. These associations were observed between trials and were more subject to ecological and
publication biases. The slope of the regression line estimated by Law et al. was about I for every 10. whereas
the association we observed for indapamide was steeper (about I mm Hg response increase for every 3 mm
Hg SBP limits of the parallel group approach and strongly supports the idea of exploring difference within
individuals of BP response to drugs.
Information on ethnicity was not collected during the trial, the main reason being that this collection is
forbidden by default in France in medical s. This is a remarkable limitation because of the knowledge that
African- people respond differentially to BP-lowering drugs. From an informal survey of investigators, black
people were not or very little represented in each centre, leading to a figure of 1 or 2% of the overall study
population, so not susceptible to have significantly influenced the presented results.
The IDEAL Trial has a relative lack of power, compared with the sample size (400 patients) that we had
initially hoped for. The selection process led to an over-representation of men, who displayed a significantly
reduced response to both drugs on average. This shows how difficult it is to explore determinants of drug
response, because this determination cannot result from a totally controlled experiment. Response markers are
represented differently in different trial populations. Exploring the reproducibility of the results f from one
clinical trial is really important, and could and should be achieved by comparing these results to other trial
results in the form of a meta-analysis on individual patient data. More powerful trials have to be set up and
will benefit from the hypothesis generated formerly in smallest trials such as IDEAL and others as well as
from the results of an ongoing meta-analysis of trial with similar objectives
(http://www.pharmgkb.org/page/icaps). Industry sponsors have no reason to be motivated by discovering BP
response markers, because of the potential negative impact on the market, which could result from such a
discovery. However, owing to the potential impact of these discoveries, trial results should be pooled at the
individual patient data level regardless of trial results and sponsor. We believe these results should be
completed by further biological and genetic analyses to obtain a satisfactory set of response markers and then
be assembled within predictive scores useful in orienting the choice of the first-line drug to be used. This
would result in better BP control and in turn better cardiovascular risk control, at a lesser cost with fewer drugs
and medical visits. Furthermore, these scores could be use or identifying different types of hypertension and
understand how hypertension develops.
The next steps of the IDEAL research program include exploring response markers further genetic and
biological markers of the renin-angiotensin-aldosterone system. This would allow us to understand why
women respond better than men on average, and especially in the ideal population. These results are expected
to a worldwide network to set up response score specific to antihypertensive drug mechanism of action.
8.0 References
1.) BE CKE-R CG MURPHY GE: Demonstration of contractile protein in endothelium and cells of the heart
valves, endocardium, intima, arteriosclerotic plaques and Aschoff bodies of rheumatic heart disease. Am J
Pathol 55: 1, 1969
2.) CONSTANTINIDES P. ROBINSON M: Ultrastructural injury of arterial endothelium. I. Effects of pH,

osmolarity, anoxia and temperature. Arch Pathol 88: 99, 1969
3.) HAUST MD, MORE RH, MOVAT HZ: The role of smooth muscle cells in the fibrogenesis of
arteriosclerosis. Am J Pathol 37: 377, 1960
4.) CEER JC. MCGILL HC JR, STRONG JP: The role of smooth muscle cells in the fibrogenesis
atherosclerotic lesions. Am J Pathol 31: 263, 1961
5). THOMAS WA, FLORENTIN RA, NAM SC. KIM DN, JONES RM, LEE KT: Preproliferative phase of
atherosclerosis in swine fed cholesterol. Arch Pathol 86: 621, 1968
6.) JARMOLYCH, DAOUD AS, LANDAU J. FRITZ KE, MELENE E: Aortic media explants. Cell
proliferation and production of mucopolysaccharides, collagen and elastic tissue. Exp Mol Pathol 9: 171. 1968
7.) WISSLER RW. The arterial medial cell, muscle or multifunctional mesenchyme. J Atheroscler Res 8: 201,
1968
8.) SCOTT RF, MORRISON ES, KROMS M: Aortic ne. respiration J Atheroscler and glycolysis Res 9: 5,
1969
9.) MUSTARD JF, PACKHAMI MA: Thromboembolism. A Manifestation of the response of blood to injury.
Circulation 42: 1. 1970
10.) KRITCHVESKY D, TEYPER SA. VESSLINOVITCH1D WISSLERRW: Cholesterol vehicle in

experimental atherosclerosis. Atherosclerosis l4 53, 1971
11.) DESHiUEKH K, NIMMI ME: A defect in the intramolecular and intermolecular cross-linking of collagen
caused by penicillamine. J Biol Chem 244: 1787, 1969
12.) HARRIS ED JR. SJOERDSMA A: Effect o of penicillamine on human collagen and its possible
application to treatment of scleroderma. Lancet 2: 996, 1966
13.) PAGE IH, MCCUBBIN JW I Renal Hypertension. Chicago, Year Book Medical Publishers, 1968
14.) BRONTE-STEWART B, HEPTINSTALL RH: The relationship between experimental hypertension and
cholesterol-induced atheroma in rabbits. J Pathol Bacteriol 68:407, 1954
15.) WAKERLIN GE, Moss WG, KIELY MS: Effect of experimental renal hypertension on experimental
thiouracil-cholesterol atherosclerosis in doges Circ Res. 5:426,1957
16.) WOLINSKY H: Response of the rat aorta media to hypertension. Circ Res 26: 507, 1970
17.) TOBIAN L, BINION J: Artery wall electrolytes in renal and DCA hypertension. J Clin Invest 13: 1407,
1954
18.) DUNCAN L.E: Mechanical factors in the localization of atheromatic. In Evolution of the Atherosclerotic
Plaque, edited by IONEs RJ. Chicago University of Chicago Press, 1963
19.) BJORKERND S, BONDIERS C: Arterial repair and atherosclerosis after mechanical injury.
Atherosclerosis 13: 355, 1971
20.) FRY DL: Certain histological and chemical responses of the vascular interface to acutely
induced.
CHEMIST DATA FORM
Survey of various ANTI HYPERTENSIVE Drugs
Name of Chemist: -
Address: -
Which would you like to prescribe
GENERIC MAME BRAND NAME
Clonidine Catapres, Catapres TTS (patch), Duraclon, Dixarit,

Kapvay, Nixiclon XR
Guanabenz Wytensin
Guanfacine Intuniv, Tenex
Metyldopa Aldomet
Chlorthalidoe Lupiclor
Lofexidine Britlofex
Telmisartan Telma
Reasons for Prescribing: -
• Less side effects

• Cost
• Patient Compliance
• Frequent visit of Representation
• Dose Convenience
WEEKLY DATA FORM
Name of Chemist: -
Address: -
Sr.No. Brand name 1st 2nd 3rd 4th 5th 6th 7th 8th
week week week week week week week week
1.) Kapvay
2.) Wytensin
3.) Tenex
4.) Aldomet
5.) Britlofex
6.) Lupiclor
7.) Catapres
8.) Telma
Chemist Sign.: - Survey by: -
Date: - Yash Vardhan Sharma
CHEMIST DATA FORM
Name of Chemist: -
Address: -

Kapvay, Nixiclon XR
Guanabenz Wytensin
Metyldopa Aldomet
Telmisartan Telma

• Cost
WEEKLY DATA FORM
Name of Chemist: -
Address: -
1.) Kapvay
2.) Wytensin
3.) Tenex
4.) Aldomet
5.) Britlofex
6.) Lupiclor
7.) Catapres
8.) Telma
CHEMIST DATA FORM
Name of Chemist: -
Address: -

Kapvay, Nixiclon XR
Guanabenz Wytensin
Metyldopa Aldomet
Telmisartan Telma

• Cost
WEEKLY DATA FORM
Name of Chemist: -
Address: -
1.) Kapvay
2.) Wytensin
3.) Tenex
4.) Aldomet
5.) Britlofex
6.) Lupiclor
7.) Catapres
8.) Telma
CHEMIST DATA FORM
Name of Chemist: -
Address: -

Kapvay, Nixiclon XR
Guanabenz Wytensin
Metyldopa Aldomet
Telmisartan Telma

• Cost
WEEKLY DATA FORM
Name of Chemist: -
Address: -
1.) Kapvay
2.) Wytensin
3.) Tenex
4.) Aldomet
5.) Britlofex
6.) Lupiclor
7.) Catapres
8.) Telma
CHEMIST DATA FORM
Name of Chemist: -
Address: -

Kapvay, Nixiclon XR
Guanabenz Wytensin
Metyldopa Aldomet
Telmisartan Telma

• Cost
WEEKLY DATA FORM
Name of Chemist: -
Address: -
1.) Kapvay
2.) Wytensin
3.) Tenex
4.) Aldomet
5.) Britlofex
6.) Lupiclor
7.) Catapres
8.) Telma
CHEMIST DATA FORM
Name of Chemist: -
Address: -

Kapvay, Nixiclon XR
Guanabenz Wytensin
Metyldopa Aldomet
Telmisartan Telma

• Cost
WEEKLY DATA FORM
Name of Chemist: -
Address: -
1.) Kapvay
2.) Wytensin
3.) Tenex
4.) Aldomet
5.) Britlofex
6.) Lupiclor
7.) Catapres
8.) Telma
CHEMIST DATA FORM
Name of Chemist: -
Address: -

Kapvay, Nixiclon XR
Guanabenz Wytensin
Metyldopa Aldomet
Telmisartan Telma

• Cost
WEEKLY DATA FORM
Name of Chemist: -
Address: -
1.) Kapvay
2.) Wytensin
3.) Tenex
4.) Aldomet
5.) Britlofex
6.) Lupiclor
7.) Catapres
8.) Telma

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FINAL DISSERTATION REPORT FOR THE PROJECT ENTITLED

“MARKETING SURVEY OF ANTIHYPERTENSIVE DRUGS”

Submitted for partial fulfilment of award of

Under the supervision of

This is to certify that the project work entitled "MARKETING RESEARCH ON

Date: Forwarded by:

This is to certify that this project entitled “MARKETING RESEARCH ON

Date: Mr. Prashant Dhakkad

It gives me immense gratification to place on records my profound gratitude and sincere

YASH VARDHAN SHARMA

Chapter Description Page no.

1.1. Choice of Initial Medication

1.2. Patient Factors Affecting Antihypertensive Drug Choice

2.0 Study Population

To prevent potential confounding by comorbidities in the prescription patterns of antihypertensive agents at

2.1 Prescription Pattern of new Cases of Hypertension

2.2. Statistical analysis

3.0. Antihypertensive Prescriptions Among Newly-diagnosed Patients

Prescription patterns of antihypertensive therapies for newly-diagnosed uncomplicated hypertension patients,

*Total sample number = 6536 patients.

*Significant p-value with the Bonferroni-adjusted a-level, p < 0.0025

Distribution of antihypertensive drugs for newly-diagnosed uncomplicated hypertension patients, by gender,

*Total sample number - 6536 patients.

3.1. Mono- therapies for New Cases of Uncomplicated Hypertension

3.2. Daily Drug Costs for Different Antihypertensive Mono-Therapies

3.3. Factors associated with initial ARB mono-therapy prescriptions

4.0. Hypertension Improvement Project (HIP)

4.1. Enrollment and Randomization

4.2.2 Physician Measurements

4.2.3 Patient Measurements

4.2.5 Power and Statistical Analysis

5.0 Study design

5.1 Study population

5.3. Explanatory variables

5.4. Statistical analysis

Response to drug and other determinants of BP

With a full-analysis population of 12 patients displaying an average placebo-controlled BP response of -7.2/-

2.) CONSTANTINIDES P. ROBINSON M: Ultrastructural injury of arterial endothelium. I. Effects of pH,

10.) KRITCHVESKY D, TEYPER SA. VESSLINOVITCH1D WISSLERRW: Cholesterol vehicle in

CHEMIST DATA FORM

Survey of various ANTI HYPERTENSIVE Drugs

Which would you like to prescribe

GENERIC MAME BRAND NAME

Clonidine Catapres, Catapres TTS (patch), Duraclon, Dixarit,

Guanfacine Intuniv, Tenex

Reasons for Prescribing: -

• Less side effects

WEEKLY DATA FORM

Survey of various ANTI HYPERTENSIVE Drugs

Chemist Sign.: - Survey by: -

Date: - Yash Vardhan Sharma

CHEMIST DATA FORM

Survey of various ANTI HYPERTENSIVE Drugs

Which would you like to prescribe

GENERIC MAME BRAND NAME

Clonidine Catapres, Catapres TTS (patch), Duraclon, Dixarit,

Guanfacine Intuniv, Tenex

Reasons for Prescribing: -

• Less side effects

WEEKLY DATA FORM

Survey of various ANTI HYPERTENSIVE Drugs

Chemist Sign.: - Survey by: -

Date: - Yash Vardhan Sharma