Cost Effectiveness and Resource

Allocation BioMed Central

Research Open Access

A cost-minimization analysis of diuretic-based antihypertensive
therapy reducing cardiovascular events in older adults with isolated
systolic hypertension
G John Chen*1, Luigi Ferrucci2, William P Moran3 and Marco Pahor3

Address: 1Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, 2Laboratory of Clinical
Epidemiology, INRCA Geriatric Department, Florence, Italy and 3Department of Internal Medicine, Wake Forest University School of Medicine,
Winston-Salem NC, USA
Email: G John Chen* - [email protected]; Luigi Ferrucci - [email protected]; William P Moran - [email protected];
Marco Pahor - [email protected]
* Corresponding author

Published: 25 January 2005 Received: 03 August 2003

Accepted: 25 January 2005
Cost Effectiveness and Resource Allocation 2005, 3:2 doi:10.1186/1478-7547-3-2
This article is available from: http://www.resource-allocation.com/content/3/1/2
© 2005 Chen et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background: Hypertension is among the most common chronic condition in middle-aged and
older adults. Approximately 50 million Americans are currently diagnosed with this condition, and
more than $18.7 billion is spent on hypertension management, including $3.8 billion for
medications. There are numerous pharmacological agents that can be chosen to treat hypertension
by physicians in clinical practices. The purpose of this study was to assess the cost of alternative
antihypertensive treatments in older adults with isolated systolic hypertension (ISH).
Method: Using the Systolic Hypertension in the Elderly Program (SHEP) and other data, a cost-
minimization analysis was performed. The cost was presented as the cost of number-needed-to
treat (NNT) of patients for 5 years to prevent one adverse event associated with cardiovascular
disease (CVD).
Result: It was found that the cost of 5 year NNT to prevent one adverse CVD event ranged widely
from $6,843 to $37,408 in older patients with ISH. The incremental cost of the 5 year NNT was
lower to treat older patients in the very high CVD risk group relative to patients in the lower CVD
risk group, ranging from $456 to $15,511. Compared to the cost of the 5 year NNT of other
commonly prescribed antihypertensive drugs, the cost of SHEP-based therapy is the lowest. The
incremental costs of the 5 year NNT would be higher if other agents were used, ranging from
$6,372 to $38,667 to prevent one CVD event relative to SHEP-based drug therapy.
Conclusion: Antihypertensive therapy that is diuretic-based and that includes either low-dose
reserpine or atenolol is an effective and relatively inexpensive strategy to prevent cardiovascular
events in older adults with isolated systolic hypertension. Use of the diuretic-based therapy is the
most cost-effective in patients at high risk for developing cardiovascular disease.

Background tions in middle-aged and older adults. Approximately 50

Hypertension is among the most common chronic condi- million Americans are currently diagnosed with this

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condition, and more than $18.7 billion is spent on hyper- subject's demographics, medical conditions, health
tension management, including $3.8 billion for behaviors, and cardiovascular risk factors were obtained.
medications[1]. Methods of these measurements have been reported4.
Fasting blood samples were analyzed at a central labora-
Treatment of hypertension can significantly decrease the tory, including serum glucose, lipid levels, creatinine, uric
risk of developing CVD [2,3]. The SHEP and other studies acid, sodium, and potassium.
have demonstrated the great potential of antihypertensive
treatments to significantly reduce the number of cardio- Of the 4,736 SHEP participants, 4,189 were included in
vascular events in elderly patients [4-10]. This, in turn, this analysis. The 547 participants were excluded either
may reduce the costs associated with this chronic condi- because of missing data concerning CVD risk factors (n =
tion. Based on the SHEP study, it is estimated that 24,000 283) or with previous CHD or stroke (n = 264). These 547
strokes, 44,000 major cardiovascular events, and 84,000 excluded subjects had similar age, sex, race, and other
admissions to the hospital could be prevented over a 5- characteristics as those who were included in this analysis.
year period [7].
Intervention
Currently, primary care physicians can choose from A stepped-care treatment approach was used, with the
numerous pharmacological agents to treat hypertension. goal for individuals with SBP >180 mm Hg to reduce to
The commonly used antihypertensive drug classes include <160 mm Hg and for those with SBP between 160 and
diuretics, beta-blockers, angiotensin-converting enzyme 179 mm Hg to have a reduction of at least 20 mm Hg. All
(ACE) inhibitors, alpha-blockers, and calcium channel participants were given chlorthalidone, 12.5 mg/d, or
blockers. Selection of an evidence-based therapy with matching placebo (step 1 and dose 1 medication). Drug
demonstrated efficacy, safety, and low cost has important dosage (step 1 and dose 2 medication) was doubled, 25
economic implications. The purpose of this study was to: mg/d, for participants failing to achieve the SBP goal at the
1) assess cost of the SHEP-based antihypertensive treat- follow-up visits. If the SBP goal was not reached at the
ment to prevent adverse events associated with CVD, maximal dose of step 1 medication, atenolol, 25 mg/d, or
including death, stroke, myocardial infarction, and heart matching placebo was added (step 2 and dose 1 medica-
failure; and 2) to compare cost of the SHEP-based treat- tion). When atenolol was contraindicated, reserpine, 0.05
ment to the costs of other commonly used antihyperten- mg/d, or matching placebo could be substituted. When
sive agent treatments. required to reach the blood pressure goal, the dosage of
the step 2 drug could be doubled (atenolol 50 mg/d or
Method reserpine 0.10 mg/d, step 2 and dose 2 medication).
The SHEP trial is a randomized, double-blind, placebo- Potassium supplements were given to all participants who
controlled clinical trial sponsored by the National Heart, had serum concentration below 3.5 mm0l/L at two con-
Lung, and Blood Institute and the National Institute on secutive visits. The SHEP participants were followed up
Aging that tested the efficacy of diuretic-based stepped- monthly until SBP reached the goal or until the maximum
care antihypertensive drug treatment of isolated systolic level of stepped-care treatment was reached [4,7]
hypertension (ISH) to prevent strokes [4].
Ascertainment of Outcome Events
Study Population The present analysis focused on five types of events: 1)
The study subjects consisted of community-dwelling men death; 2) first-occurring major cardiovascular event,
and women 60 years and older who had isolated systolic including stroke, MI, or heart failure; 3) first-occurring
hypertension, defined as an average systolic blood pres- stroke; 4) first-occurring MI; and 5) first clinical diagnosis
sure (SBP) ≥ 160 mm Hg and an average diastolic blood of congestive heart failure (CHF). The adjudication and
pressure (DBP) < 90 mm Hg over 2 baseline visits. The pri- clarification of the events was done by a panel of three
mary endpoint of the trial was combined nonfatal and physicians blinded to treatment assignment and blood
fatal stroke over a 5-year period. Secondary endpoints pressure status. Members of the panel reviewed the docu-
included nonfatal myocardial infarction (MI) plus fatal mentation of new cardiovascular events over the study
coronary heart disease (CHD) and major cardiovascular period and adjudicated outcome events according to pre-
disease (CVD) morbidity and mortality. A total of 2,365 determined criteria. [4]
and 2,371 persons were randomized into the treatment
and placebo group of the study respectively. Calculation of Global CVD Risk Scores
Information at the baseline on age, sex, total cholesterol,
Subjects who met the preliminary blood pressure (BP) eli- high density lipid (HDL) cholesterol, systolic blood pres-
gibility criteria at the initial contact visit were referred to sure, diabetes (diabetic vs. non-diabetic), and smoking
SHEP clinics for the baseline visits. At the baseline visits, (current vs. never or past smoking) were used to calculate

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an a priori global score for the risk of developing future mg/d plus atenolol 50 mg/d or reserpine 0.1 mg/d. Direct
cardiovascular events, according to the Multiple Risk Fac- drug acquisition costs were calculated based on the mini-
tor Assessment Equation jointly proposed by the Ameri- mum average wholesale prices (AWP) within drug manu-
can Heart Association and the American College of facturers in the year 2000.[13] All drug costs were based
Cardiology.[11] The equation assigns scores to major risk on the AWP per unit dose. The expected cost (EC) of the
factors, using cut points that were originally developed SHEP drug acquisition per patient in 1 year was calculated
using data on incident CHD from the Framingham study. as follows:
A global CVD risk score ranging from -17 to +22 was
obtained by adding the subscores. Higher values reflect a EC = W1 × C1 + W2 × C2 + W3 × C3 + W4 × C4
more unfavorable risk profile. Because the equation does
not provide the age score for persons ≥ 75 years of age The W1, W2, W3, and W4 represent proportions of the
(28.5% of the SHEP study population), one additional participants using the Step 1 and Dose 1, the Step 2 and
point was assigned to men and women in this age group. Dose 2, the Step 2 and Dose 1, and the Step 2 and Dose 2
Based on the global cardiovascular risk score, participants medication, respectively. C1, C2, C3, and C4 represent the
were classified into one of four CVD risk groups: low, drug acquisition cost of the Step 1 and Dose 1, the Step 2
medium, high and very high. and Dose 2, the Step 2 and Dose 1, and the Step 2 and
Dose 2 medication, respectively. A Monte Carlo method
Calculation of Costs was performed to estimate the average cost and its stand-
The methods of economic evaluation include cost-effec- ard deviation.
tiveness analysis, cost-utility analysis, and cost-benefit
analysis, which can be used to assess the trade-off between To compare the cost of the SHEP-based therapy to other
costs and benefits in choices of antihypertensive treat- antihypertensive drugs, it was assumed that all antihyper-
ment regimens. The primary aim of this analysis was to tensive drugs in the comparisons have equal efficacy in
examine cost of the diuretic-based antihypertensive drug terms of the NNT for 5 years to prevent one CVD related
intervention in the SHEP trial. A cost-minimization anal- event. The NNT was calculated based on the method. [12]
ysis is a special type of cost-effectiveness analysis. It can be
used to compare cost difference among competing alter- All drug costs were expressed as dose-specific cost per
natives of antihypertensive drug treatments when these patient in 1-year and/or 5-year. Using the approach, costs
treatments are medically equivalent. In this study, we used were calculated for each representative drug based on
cost-minimization analyses to compare costs and incre- equipotent doses in terms of blood pressure reduction.
mental costs of NNT for 5 years to prevent one adverse [14] The non-SHEP based drugs, including beta-blockers
event related to CVD among antihypertensive treatment (Atenolol), ACE inhibitors (Enalapril), and calcium chan-
regimens. The perspective of this economic evaluation nel blockers (Nifedipine), were selected in the analysis
was that of a national health insurance system. according to antihypertensive drug class. These drugs were
considered commonly prescribed antihypertensive medi-
We used the number-needed-to-treat as an unit of com- cations in clinical practices. [14] All costs were adjusted in
mon outcome measure in the analysis. The number- 2000 constant U.S. dollars using the Consumer Price
needed-to-treat to prevent one adverse outcome has Index.
become a widely used measure of treatment benefits
derived from the results of clinical trials. The NNT is the In this analysis, we focused on the drug acquisition cost
reciprocal of the absolute risk reduction (ARR) which is for antihypertensive management. Therefore, the moni-
the difference between the proportions with the adverse toring cost for antihypertensive treatment was not
event in the treatment and placebo groups. The 95% con- included. Total treatment cost includes antihypertensive
fidence interval of NNT was calculated based on the drug cost and monitoring cost. The monitoring of treat-
regression-based method described by Laupacis et al. [12] ment in ambulatory care settings including physician vis-
its and laboratory tests have an estimated cost of $284 per
The cost specified in the analysis includes the drug acqui- patient per year. [14] Total cost of the NNT for 5 years of
sition cost of SHEP treatment from the perspective of a each drug therapy was calculated by multiplying the NNT
national health insurance system. According to the SHEP for 5 years with the drug acquisition cost for 5 years per
treatment protocol, the stepped-care was classified into patient. The incremental cost is the cost of NNT for 5 years
four types of drug treatments: 1) the Step 1 and Dose 1: to prevent one adverse event of one alternative less the
chlorthalidone 12.5 mg/d; 2) the Step and Dose 2: chlo- cost of the base case. In calculations of the incremental
rthalidone 25 mg/d; 3) the Step 2 and Dose 1: chlortha- costs of the NNT for 5 years by types of outcome, the cost
lidone 25 mg/d plus atenolol 25 mg/d or reserpine 0.05 to prevent one stroke which was used as a base case. In cal-
mg/d; and 4) the Step 2 and Dose 2: chlorthalidone 25 culations of the incremental costs of the NNT for 5 years

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Table 1: Estimated Drug Acquisition Costs of The SHEP Treatment Protocol

Drug Category Drug Cost Per Patient in 1 Year Proportion Drug Cost Per Patient in 5 years

step1 dose1 (chlorthalidone 12.5 mg/d) $10.24 0.43

step1 dose2 (chlorthalidone 25 mg/d) $20.48 0.23
step2 dose1 (chlorthalidone 25 mg/d plus $222.45 0.16
atenolol 25 mg/d or reserpine 0.05 mg/d)
step2 dose2 (chlorthalidone 25 mg/d plus $221.93 0.17
atenolol 50 mg/d or reserpine 0.1 mg/d)

Weighted SHEP Rx $83.29 0.91

KCL $88.33 0.09

Weighted SHEP Rx including KCL $91.24 $456

SD $101.78

Table 2: NNT and Drug Costs by Adverse Events

Event Placebo risk Treatment ARR NNT (95% CI) 5-Year 5-year Rx Total Cost Incremental
risk NNT Cost Per Cost
Patient

Death 0.1002 0.0858 0.0144 69 (31 – 319) 62 $456 $28,284 $13,230

CVD 0.1746 0.1147 0.0599 17 (12 – 26) 15 $456 $6,843 -
Stroke 0.0705 0.0433 0.0272 37 (24 – 76) 33 $456 $15,055 $0 (base)
MI 0.0312 0.0202 0.011 91 (48 – 740) 82 $456 $37,408 $22,354
CHF 0.0397 0.0198 0.0199 50 (33 – 103) 45 $456 $20,529 $5,474

by risk levels of CVD, the cost to prevent one adverse event The cost for the 5 year NNT to prevent one patient from
of the very high risk level being used as a base case. one CVD event of any type is about four times lower than
that of death. The cost for the 5 year NNT to prevent one
Result MI is much higher than the cost for preventing one stroke
Table 1 shows the expected acquisition cost of the diu- or one CHF. Using the cost to prevent one stroke as the
retic-based antihypertensive therapies. The step 1 and base amount, the incremental cost for the NNT for 5 years
dose 1 medication was the most used therapy and fol- to prevent one MI or one CHF was $22,354 and $5,474,
lowed by the step 1 and dose 2 medication. The annual respectively.
drug acquisition costs of the step 1 and dose 1, the step 1
and dose 2, the step 2 and dose 1 and the step 2 and dose Table 3 presents costs of the NNT for 5 years to prevent
2 were $10.24, $20.48, and $222.45 respectively. The one CVD event of any type by CVD risk strata. The cost for
expected annual drug acquisition cost per patient of the the 5 year NNT increases as the CVD risk level decreases.
SHEP treatment without potassium supplements was $83 It costs $20,529 for the 5 year NNT to prevent one of any
and with potassium supplements was $91. The 5 year type of CVD adverse events among patients in the low
annual drug acquisition cost with potassium supplements CVD risk group. In contrast, it only costs $5,018 for the
per patient was $456. same effect among patients in the very high CVD risk
group. Using the cost of the very high CVD level as a base,
Results of the 5 year NNT to prevent one adverse event if 12 patients in the high CVD level are treated, the extra
and its associated cost by event type are shown in Table 2. cost to prevent one patient out of 12 from one CVD event
To prevent one death, the cost for the 5 year NNT was is $456. The extra cost for patients in the low CVD risk
$28,284. In other words, we need to treat 62 patients for group to receive the same effect is $15,511 relative to the
5 years in order to prevent one of them from death and the patients in the very high CVD risk group.
expected drug acquisition cost for the benefit is $28,284.

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Table 3: NNT and Drug Costs by CVD Risk Profile

Risk Placebo Risk Treatment ARR NNT (95% CI) 5-year NNT 5-year Drug Total Cost Incremental
Category Risk Cost Per Cost
Patient

1 (low) 0.1013 0.0814 0.0199 50 (18 – 59) 45 $456 $20,529 $15,511

2 (medium) 0.1476 0.0912 0.0564 18 (11 – 53) 16 $456 $7,299 $2,281
3 (high) 0.2044 0.1265 0.0779 13 (8 – 26) 12 $456 $5,474 $456
4 (very high) 0.2526 0.1699 0.0827 12 (7 – 38) 11 $456 $5,018 $0 (base)

Table 4: Comparisons of Drug Acquisition Costs of 5-Year NNT Among Antihypertensive Drug Classes

Drug Class Commonly 5-year Cost Per 5-Year NNT Total Cost Incremental Cost Ratio
Prescribed Patient Cost

SHEP-based drug therapy $456 15 $6,843 $0 (base) 1 (base)

Beta-Blocker Atenolol
25 mg daily $1,255 15 $18,825 $11,982 2.75
50 mg daily $1,245 15 $18,675 $11,832 2.73
100 mg daily $1,792 15 $26,880 $20,037 3.93

ACE inhibitor Enalapril

5 mg daily $2,031 15 $30,465 $23,622 4.45
10 mg daily $2,132 15 $31,980 $25,137 4.67
20 mg daily $3,034 15 $45,510 $38,667 6.65

Alpha-Blocker Terazosin
2 mg daily $2,984 15 $44,760 $37,917 6.54
5 mg daily $2,984 15 $44,760 $37,917 6.54
10 mg daily $2,984 15 $44,760 $37,917 6.54

Calcium channel blocker Nifedipine

30 mg daily $881 15 $13,215 $6,372 1.93
60 mg daily $1,762 15 $26,430 $19,587 3.86
90 mg daily $2,644 15 $39,660 $32,817 5.8

In Table 4, the comparisons of the incremental drug Discussion

acquisition cost for the 5 year NNT of the SHEP-based The result of an economic evaluation essentially shows
antihypertensive therapy to other commonly prescribed the cost per benefit gained from adapting a specific treat-
antihypertensive drugs. This analysis assumes that alterna- ment. The effective and efficient use of resources has been
tive drugs have equal efficacy to prevent CVD events. The increasingly emphasized from society, health plans, and
estimated incremental net cost of the 5 year NNT to pre- health care providers. This cost-minimization analysis
vent one CVD event associated with use of atenolol (beta- incorporating outcome data from the SHEP trial presents
blocker), enalapril (ACE inhibitor), terazosin (alpha- information treatment cost for older patients with ISH.
blocker), and nifedipine (calcium channel blocker) rela- We found that a long-term, low-dose and diuretic-based
tive to the SHEP-based drug therapy ranged from $6,372 antihypertensive therapy is relatively inexpensive and
to $38,667 in older adults with isolated systolic hyperten- effectively prevents adverse events associated with cardio-
sion. According to the cost ratio, it indicates that the costs vascular diseases, especially in older patients who had a
of the 5 year NNT of using enalapril, terazosin, and high CVD risk profile.
nifedipine were up to 6.6 times more expensive compared
to the SHEP-based drug therapy.

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Our findings indicate that the total and incremental treat- The results of this study are limited to men and women 60
ment costs of antihypertensive drugs in ambulatory care years and older who have isolated systolic hypertension
settings range widely among drug classes as well as within and no presumed contraindication to any one class of
drug classes. This analysis suggests that diuretic-based antihypertensive medications. One limitation to our
antihypertensive treatments are the least expensive, study relates to the fact that comparisons were based on
whereas atenolol (beta-blocker) is less costly than enal- costs of monotherapies, while combination therapies are
april (ACE inhibitor) and nifedipine (calcium channel frequently needed to control blood pressure.
blocker), and terazosin (alpha-blocker) is the most expen-
sive drugs in terms of the 5 year NNT to prevent one CVD The number-needed-to-treat to prevent one adverse out-
event. It appears that use of the SHEP-based drug therapy come has become a widely used measure of treatment
offers greater economic benefits for controlling isolated benefits in medical community, which is easy for physi-
systolic hypertension in the elderly than other antihyper- cians to understand. The shortcomings of NNT are that
tensive drug treatments. Using a decision analysis model the outcome measure of an effect is with one dimension-
that simulated clinical decisions and outcomes that survival probability and that it measures the specified out-
would occur when primary care physicians follow the JNC come at a single point in time. Therefore, a measure of
IV hypertension management guidelines, it was found NNT can not capture an outcome in effectiveness of the
that a newer class of calcium channel blockers can slightly intervention with two dimensions: time and survival
increase the proportion of patients who achieve and probability. These limitations may not allow us to take
maintain hypertension control, but at a substantially time and discounting on cost and effect into account in
higher cost than with a generic diuretic drug. [15] this study.

For our analyses, we presumed that all drugs offer equiva- Conclusion
lent therapeutic benefits. This assumption may have intro- Based on our findings, antihypertensive therapy that is
duced a conservative bias into our primary findings. In diuretic-based and that includes either low-dose reserpine
fact, randomized controlled trials directly comparing or atenolol represents a cost-effective regimen in prevent-
active treatments for hypertension reported that calcium ing or delaying cardiovascular events in older adults. Use
antagonists and doxazosin were inferior to low-dose diu- of the diuretic-based therapy is the most cost-effective in
retics or other agents in preventing cardiovascular events, patients at high risk for developing cardiovascular disease.
suggesting that the cost-effectiveness of diuretic-based These results suggest that clinicians should consider using
treatments may be even more favorable than estimated in diuretics plus low-dose reserpine or atenolol as first-line
the present study. [15-17] Further, in a meta-analysis of therapy in patients with isolated systolic hypertension
over 27,000 patients, those randomized to calcium antag- who are greater than 60 years old when there are no con-
onists as first-line therapy ran a greater risk of experienc- traindications among these patients.
ing a myocardial infarction (26% higher risk), congestive
heart failure (25% higher risk), and all cardiovascular List of Abbreviations Used
events combined (10% higher) as compared to those ran- ACE: angiotensin-converting enzyme
domized primarily to low-dose diuretics, beta-blockers
and ACE inhibitors.[16] Finally, the Antihypertensive and ALLHAT: Antihypertensive and Lipid Lowering treatment
Lipid Lowering treatment to prevent Heart Attack Trial to prevent Heart Attack Trial
(ALLHAT) recently reported a significantly higher risk of
congestive heart failure, stroke, and major cardiovascular ARR: absolute risk reduction
events in the doxazosin group than in the chlorthalidone
group.[17] It is noteworthy that in this trial, only minimal AWP: average wholesale price
differences in blood pressure control occurred between
treatment groups, suggesting that the magnitude of blood BP: blood pressure
pressure control represents an inadequate marker for
comparing the therapeutic benefits of antihypertensive CHD: coronary heart disease
therapies.
CHF: congestive heart failure
With regard to costs projected in our study, it is notewor-
thy to consider that compared to the SHEP treatments, CVD: cardiovascular disease
costs of treatments based on more recently developed
antihypertensive agents (than reported here) are likely to DBP: diastolic blood pressure
be even higher than estimated in the present analyses.
HDL: high density lipid

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ISH: isolated systolic hypertension 9. The Systolic Hypertension in the Elderly Program Cooperative
Research Group: Implications of the Systolic Hypertension in
the Elderly Program. Hypertension 1993, 21:335-343.
JNC IV The Sixth Report of the Joint National Committee 10. Savage PJ, Pressel SL, Curb JD, Schron EB, Applegate WB, Black HR,
on Prevention, Detection, Evaluation, and Treatment of Cohen J, Davis BR, Frost P, Smith W, Gonzalez N, Guthrie GP, Ober-
man A, Rutan G, Probstfield JL, Stamler J: Influence of long-term,
High Blood Pressure. low-dose, diuretic-based, antihypertensive therapy on glu-
cose, lipid, uric acid, and potassium levels in older men and
NNT: number-needed to treat women with isolated systolic hypertension: The Systolic
Hypertension in the Elderly Program. Archives of Internal
Medicine 1998, 158:741-751.
SBP: systolic blood pressure 11. Grundy SM, Parternak R, Greeland P, Smith S, Fuster V: Assessment
of cardiovascular risk by use of multiple-risk-factor assess-
ment equation. A statement for healthcare professionals
SHEP: Systolic Hypertension in the Elderly Program from the American Heart Association and the American
College of Cardiology. Circulation 1999, 100:1481-1492.
12. Laupacis A, Sackett DL, Roberts RS: An assessment of clinically
Conflict of Interest useful measures of the consequences of treatment. New Eng-
The author(s) declare that they have no competing land Journal of Medicine 1988, 318:1728-1733.
13. Drug topics red book Montvale, NJ, Medical Economics Co; 2000.
interests. 14. Pearce KA, Furberg CD, Psaty BM, Kirk J: Cost-minimization and
the number of needed to treat in uncomplicated
Authors' contributions hypertension. American Journal of Hypertension 1998, 11:618-629.
15. Ramsey SD, Neil N, Sullivan SD, Perfetto E: An economic evalua-
GC, LF, WM and MP participated the development of the tion of the JNC hypertension guidelines using data from a
analytic framework. GC performed all data analyses. GC, randomized controlled trial. Journal of American Board Family
LF, WM and MP drafted and revised the manuscript. All Practice 1999, 12:105-114.
16. Pahor M, Psaty B, Alderman MH, Williamson JD, Applegate WB,
authors approved the final manuscript. Cavazzini C, Furberg CD: The health outcomes associated with
calcium antagonists compared with other first-line antihy-
pertensive therapies: a meta-analysis of randomized control-
Acknowledgements led trials. Lancet 2000, 356:1949-1954.
The SHEP was supported by a contract with the National Heart, Lung, and 17. The ALLHAT Collaborative Research Group: Major cardiovascu-
Blood Institute and the National Institute on Aging. This study was sup- lar events in hypertensive patients randomized to doxazosin
ported by a grant NHLBI R03 HL5995-01A1 to Wake Forest University versus chlorthalidone in Antihypertensive and Lipid Lower-
ing treatment to prevent Heart Attack Trial (ALLHAT):
Health Sciences, Winston-Salem, North Carolina.
preliminary results. JAMA 2000, 283:1967-1975.

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WH, Bulpitt CJ, De Leeuw PW, Dollery CT, Fletcher AE, Forette F, disseminating the results of biomedical researc h in our lifetime."
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hto J, Zanchetti A: Randomized double-blind comparison of
placebo and active treatment for older patients with isolated Your research papers will be:
systolic hypertension. Lancet 1997, 350:757-764.
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8. Celis H, Yodfat Y, Thijs L, Clement D, Cozic J, De Cort P, Forette F,
Gregoire M, Heyrman J, Stibbe G, Van den Haute M, Staessen J, peer reviewed and published immediately upon acceptance
Fagard R: Antihypertensive therapy in older patients with iso-
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