Download Cost-Effectiveness Analysis of Hypertension Guidelines

Cost-Effectiveness Analysis of Hypertension Guidelines in
South Africa
Absolute Risk Versus Blood Pressure Level
Thomas A. Gaziano, MD, MSc; Krisela Steyn, MSc, NED, MD; David J. Cohen, MD, MSc;
Milton C. Weinstein, PhD; Lionel H. Opie, MD, DPhil, FRCP
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Background—Hypertension is responsible for more deaths worldwide than any other cardiovascular risk factor. Guidelines
based on blood pressure level for initiation of treatment of hypertension may be too costly compared with an approach
based on absolute cardiovascular disease (CVD) risk, especially in developing countries.
Methods and Results—Using a Markov CVD model, we compared 6 strategies for initiation of drug treatment—2 different
blood pressure levels (160/95 and 140/90 mm Hg) and 4 different levels of absolute CVD risk over 10 years (40%, 30%,
20%, and 15%)—with one of no treatment. We modeled a hypothetical cohort of all adults without CVD in South
Africa, a multiethnic developing country, over 10 years. The incremental cost-effectiveness ratios for treating those with
10-year absolute risk for CVD ⬎40%, 30%, 20%, and 15% were $700, $1600, $4900, and $11 000 per quality-adjusted
life-year gained, respectively. Strategies based on a target blood pressure level were both more expensive and less
effective than treatment decisions based on the strategy that used absolute CVD risk of ⬎15%. Sensitivity analysis of
cost of treatments, prevalence estimates of risk factors, and benefits expected from treatment did not change the ranking
of the strategies.
Conclusions—In South Africa, current guidelines based on blood pressure levels are both more expensive and less
effective than guidelines based on absolute risk of cardiovascular disease. The use of quantitative risk-based guidelines
for treatment of hypertension could free up major resources for other pressing needs, especially in developing countries.
(Circulation. 2005;112:3569-3576.)
Key Words: cost-benefit analysis 䡲 hypertension 䡲 prevention 䡲 stroke 䡲 cardiovascular diseases
D
The other method is the blood pressure level approach,
which uses different cutpoints in blood pressure level to
define hypertension and recommend treatment. This approach
is exemplified by the American Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure (JNC VII).5 Among
those without CVD, these blood pressure level– based guidelines are primarily focused on arbitrary blood pressure levels
above which hypertension is diagnosed, with only a minor
modification if diabetes mellitus is present. Although the
blood pressure guidelines recommend the ascertainment of
other risk factors, the decision to initiate drug treatment does
not take into account this additional information, with the
exception of diabetes mellitus and chronic renal disease.
The blood pressure level–approach based on a single cutoff
point does not differentiate risk based on age, actual level of
espite advances in treatment, cardiovascular disease
(CVD) is expected to be the leading cause of death and
disability worldwide by 2020.1 Among risk factors for CVD,
hypertension is responsible for more deaths worldwide than
any other, including cholesterol, tobacco, body mass index,
and physical activity.2 Hence, the social and economic
demands of adequately treating hypertension are of considerable magnitude and complexity.
Internationally, there are 2 approaches to the primary
prevention of CVD expressed through hypertension guidelines. One approach is based on absolute risk and has been
adopted by the British Hypertension Society3 and New
Zealand.4 In this strategy, the absolute CVD risk is estimated
on the basis of the number and severity of all major risk
factors. Treatment decisions are then based on the choice of
a level of risk above which it is reasonable to attempt to lower
blood pressure with medications.
Received January 12, 2005; revision received May 19, 2005; accepted July 18, 2005.
From Cardiovascular Medicine (T.A.G.) and the Division of Social Medicine and Health Inequalities (T.A.G., M.C.W.), Brigham & Women’s Hospital,
Harvard Medical School, Boston, Mass; Chronic Diseases of Lifestyle Unit of the Medical Research Council (K.S.), Cape Town, South Africa; Cardiology
Division (D.J.C.), Beth Israel Deaconess Medical Center, Boston, Mass; Hatter Institute (L.H.O.), Department of Medicine and Cape Heart Centre,
Faculty of Health Sciences, University of Cape Town, South Africa; and Department of Health Policy and Management (M.C.W.), Harvard School of
Public Health, Boston, Mass.
Guest Editor for this article was Clyde W. Yancy, MD.
Reprint requests to Thomas A. Gaziano, MD, Cardiovascular Medicine, Brigham & Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail
[email protected]
© 2005 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/CIRCULATIONAHA.105.535922
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December 6, 2005
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cholesterol, smoking, or the number of other risk factors
present. Consequently, this method does not allow for precise
assessment of a patient’s true CVD risk. For example, the
predicted 10-year CVD risk for a patient with a systolic blood
pressure of 130/90 mm Hg and more than 1 risk factor can
range from 5% to 50%. Likewise, a patient with systolic
blood pressure of 170 mm Hg and no other risk factors can
have a 10-year risk of ⬍5% years depending on age. Thus, at
one extreme, some high-risk patients are undertreated, and at
the other extreme, many patients at relatively low risk are
treated with very little absolute benefit.
An analysis in Great Britain6 revealed that the methods of
JNC VI and the World Health Organization/International
Society Hypertension (WHO/ISH) for screening those with
more than a 20% 10-year-risk of CVD, compared with the
Framingham risk equation, had sensitivities of 80% to 90%
but specificities of 10% (JNC VI) and 50% (WHO/ISH) and
thus failed to differentiate those between high and low risk.
The health and economic implications of this poor specificity
were evaluated in the WHO CHOICE (World Health Organization Choosing Interventions that are Cost-Effective)7
program. It showed that the strategy of treating those at high
absolute risk in various regions of the world was cheaper and
saved more lives than one based on target levels of individual
risk factors. However, the model is limited by its use of
regional rather than national epidemiology and cost estimates.
These limitations are particularly important because the
distribution of hypertension differs by geography and ethnicity,8 as much as does the extent of economic development in
different countries.
Recently, the South African Hypertension Society adopted
and revised its new guidelines9,10 based on the JNC VI11 and
VII5 guidelines. Furthermore, South Africa has conducted
one of the first demographic health surveys in sub-Saharan
Africa to estimate the prevalence of hypertension and other
CVD risk factors.12 We therefore believed that this developing country with a multiethnic population provided a unique
and timely opportunity to conduct a cost-effectiveness analysis comparing the 2 approaches in a country with a growing
burden of CVD and in which epidemiological and cost data
were available to help inform the potential consequences of
the various guideline choices for hypertension.
Methods
Guidelines Compared
We conducted a cost-effectiveness analysis of blood pressure level–
and absolute risk– based hypertension guidelines in persons without
known CVD or target-organ disease. The strategies compared
included 2 different strategies based on blood pressure levels and 4
different strategies based on the absolute level of cardiovascular risk,
as well as a comparison strategy of no antihypertension prescription
therapy, for a total of 7 different strategies. The first blood pressure
level strategy was the 1995 South African Hypertension Society
guidelines.13 These guidelines recommended initiation of drug treatment for all those who have a blood pressure greater than 160/
95 mm Hg or those with a blood pressure greater than 140/90 mm Hg
and diabetes mellitus. The second blood pressure level strategy was
equivalent to the current guidelines that were adopted by the South
African Hypertension Society in 2001.9 According to the current
South African guidelines, drug treatment is initiated for those who
have a blood pressure greater than 140/90 mm Hg alone or 130/
85 mm Hg with diabetes mellitus after lifestyle changes failed to
reduce the above levels. Under the 4 strategies based on absolute risk
for CVD strategies, if an individual has an absolute risk of CVD over
the next 10 years of more than 15% (or 20%, 30%, or 40%,
depending on the specific strategy), then antihypertensive therapy is
initiated. Finally, we considered a “no-intervention” strategy in
which patients would not receive any pharmacological primary
prevention treatment for hypertension. We assumed for all strategies
that once an individual developed CVD, he or she would be treated
according to the standard of care currently in practice. Treatment
guidelines in all 7 strategies were applied to a simulated population
of all South African adults from the age of 35 to 75 years who were
free of CVD, defined as angina, myocardial infarction, sudden death,
or stroke.
South Africa CVD Risk Stratification
The population was stratified into 288 cohorts representing each of
the possible combinations of the 6 characteristics: sex, age, systolic
blood pressure, smoking, diabetes mellitus, and cholesterol. Age was
stratified into 4 deciles (35 to 44, 45 to 54, 55 to 64, and 65 to 74
years) according to the 1996 census.14 There was further stratification by systolic blood pressure into 3 groups: ⬍140 mm Hg, 140 to
59 mm Hg, and ⱖ160 mm Hg. Further dichotomization was done for
smoking and diabetes mellitus.15–17 Finally, the strata were divided
according to 3 levels of total cholesterol: ⬍5.18 mmol/L (200
mg/dL), 5.18 to 7.25 mmol/L (200 to 280 mg/dL), and
ⱖ7.25 mmol/L (280 mg/dL).18,19 The proportion in each stratum of
the cohort reflected the results of the 1998 South African Demographic and Health Survey12 for age, sex, smoking status, and blood
pressure. The distributions of cholesterol and diabetes mellitus were
stratified with mean values according to sex, because few data exist
to determine their relationship to the other risk factors.
Markov CVD Model
No cohort data exist in South Africa that show the effects of the risk
factors for CVD, nor are there any randomized control trial data on
the benefit of treatment for hypertension. There have been no trials
that compared the different hypertension guidelines. Even if these
trial data did exist, they likely would not be for the length of time we
chose to evaluate, and we therefore chose to model CVD. We used
Markov modeling, which allowed us to predict disease events over a
given length of time for a particular cohort and adjust risks as the
population aged.
The simulation began with a population free of CVD. Baseline
assumptions for the CVD model (simplified representation in Figure
1) and their sources are listed in Table 1. If under the specific set of
guidelines, the conditions for initiation of hypertensive drug treatment were met, the cohort entered into the treatment arm; otherwise,
the simulated cohort entered the no-treatment arm. For absolute risk
groups, a 10-year risk of CVD was calculated that was based on the
Framingham risk function.20
Each year, the cohort faced a probability of dying of a noncardiac
cause on the basis of South African life tables,21 developing coronary
heart disease, having a stroke, or surviving free of CVD. The risks
for an event— either coronary heart disease or stroke—were based
on separate Framingham risk functions for each event.20,22 Separate
short-term and annual survival probabilities were defined for each
cohort group based on age and sex for each coronary heart disease
outcome and for stroke. Finally, the probabilities of being admitted
to a hospital and having angiography, revascularization, or CABG
were estimated for each scenario in South Africa. Data on actual
rates do not exist, but we assumed rates equal to one tenth the US
rates in 1999 and varied these rates in sensitivity analyses.
At the end of each year, the cohort was then redistributed to 1 of
8 health states, depending on the events of the previous year. The 8
states were disease-free (no CVD event or death of other causes),
postarrest, post–myocardial infarction without CABG, post–myocardial infarction with CABG, postangina without CABG, postangina
with CABG, postcerebrovascular accident (CVA), and dead (non–
CVD-related and CVD-related death). For those in the disease-free
state, the risk factors remained the same with the exception of age,
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Figure 1. Schematic of CVD model. The
full model represented by this simplified
version has 62 possible clinical pathways. All members of the cohort begin
free of CVD disease. In the initial year,
each member of the cohort has a certain
probability based on treatment status
risk factors of moving along 1 of 4 pathways: remaining disease free, dying of
non-CVD causes, or developing fatal or
nonfatal coronary heart disease or
stroke. In the subsequent years, those
with prior CVD follow a separate pathway with adjusted risks for recurrence of
CVD or death based on age and prior
event. All risks are updated annually
based on age. Costs are captured along
the way for treatment of hypertension
and CVD events. CHD indicates coronary
heart disease; CVA, cerebrovascular
accident; Rx, treatment; and MI, myocardial infarction.
which was updated annually. For those with prior CVD, their risk
was based on their CVD history.
Total life-years and quality-adjusted life-years (QALYs) were
accumulated for the cohort over the 10 years for each guideline.
QALYs were obtained with the weighted disease state values from
the disability weights of the WHO Global Burden of Disease
project.23 All analyses were performed with DATA by TreeAge
Software Incorporated.
Treatment Assumptions
Treatment was assumed to lead to a 10-mm Hg reduction in systolic
blood pressure on the basis of the meta-analyses by MacMahon et
al24 and Collins et al.25 It was assumed that all individuals would
receive the same reduction in blood pressure from the medications
given the work in the meta-analysis by MacMahon et al.24 On the
basis of these meta-analyses, we estimated that a 10-mm Hg reduction in systolic blood pressure would result in a 40% relative risk
reduction for stroke and a 14% relative risk reduction for coronary
heart disease events.24,25
Costs
Only the costs related to treatment of hypertension, CVD events, and
their sequelae were included in the model. Screening costs included
the cost of obtaining risk factor information. Because both of the
blood pressure level– based guidelines required ascertainment of
these values, the cost of screening was the same across all strategies
except the no-intervention strategy. Productivity costs due to work
loss and costs of care giving and travel time were not included in the
analysis. The proportions of patients who received each antihypertensive drug and the average number of medications prescribed per
person were obtained from the South African Demographic Health
Survey.12 The costs of treatment for hypertension included the
number of clinic visits required for each of the guidelines. Medication costs reflected wholesale prices and administration costs.26 The
cost per visit was according to the South African “scale of benefits.”27 These are the levels that are reimbursed by third-party payers
and are considerably less than the charges recommended by the
South African Medical Association.27 Treatment costs for the morbid
sequelae of hypertension—angina, myocardial infarction, cardiac
arrest, and stroke—are not directly itemized for each diagnosis in
South Africa; however, the mean cost per CVD admission has been
estimated in South Africa.28 Relative weights for the costs of
individual diagnoses were estimated from US data.29 These relative
differences were applied to the average South African CVD admission cost to determine an estimate for each specific CVD admission.
Costs of coronary angiography, percutaneous coronary interventions,
and CABG surgery were according to the South African Medical
Association scale of benefits and included both hospital and physician costs.
Economic Analysis and Discounting
All costs are reported in 2001 US dollars. To convert costs from the
South African rand to the US dollar, costs were first converted using
the mean exchange rate for the year in which each of the South
African costs were reported. Then, the costs were adjusted to 2001
US dollars using the inflation rate for South Africa over those years
up to 2001. Both future costs and benefits were discounted at 3% per
year, consistent with current guidelines. Effects were measured in
years of life and QALYs gained. Strategies that had higher costs and
fewer QALYs than at least 1 other strategy, ie, that were dominated,
were eliminated from further consideration. Incremental costeffectiveness ratios were calculated for each of the nondominated
programs.
Sensitivity Analyses
Univariate sensitivity analyses were conducted on the costs of
hypertension treatment, the costs per hospital diagnosis, the proportion of the population that undergoes CABG or angiography, the
proportion of the population being treated for hypertension, the
prevalence of hypercholesterolemia, the relative risk reduction from
treatment, and the discount rate. We also performed a probabilistic
multivariate sensitivity analysis with Monte Carlo simulation30 in
which we simultaneously varied all of the values listed above. For
this analysis, the costs and discount rate followed a uniform
distribution over the ranges listed in Table 1, whereas the remaining
variables followed a log-normal distribution. New values from
within each of the probability distributions were randomly selected
during each of 1000 iterations, and the quality-adjusted life expectancy and lifetime cost for each of the strategies were calculated.
Model Validation
We compared projected annual mortality rates from the model for
ischemic heart disease (death due to angina, myocardial infarction, or
cardiac arrest) and stroke with the mortality rates recorded in South
Africa. We also compared the total direct costs of CVD predicted by
our model with a previously published estimate.
Results
Model Validation
Table 2 compares the projections of costs, morbidity, and
mortality from our model with the estimates from the avail-
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TABLE 1.
Estimated Base-Case Values and Assumptions for Model Input Parameters
Parameter
Value
Range for Sensitivity
Analyses
Epidemiology and treatment
Hypertension and smoking prevalence10
Age, sex, and race differences
Risk functions
10-Year cardiovascular disease risk7
Framingham risk function
7
10-Year coronary heart disease risk
Framingham risk function
10-Year stroke risk20
Framingham risk function
Noncardiovascular mortality19
Table
Proportion of eligible people receiving
antihypertensive treatment10
44%
32%–56%
Treatment effects
BP reduction24
10 mm Hg systolic
24,25
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CHD risk reduction
14%
14%–25%
Stroke reduction24,25
40%
10%–50%
$86
$ 43–$192
Costs 10,21–25
Hypertension treatment
CVD events
Average cost of CVD admission
$5636
$3150–$12 600
CHD ⬍30-day survival
$3166
$1500–$6000
CHD ⬎30-day survival
$4402
$2000–$8000
Stroke
$8633
$4000–$17 000
CABG
$11 431
$5500–$22 000
Catheter-based revascularization
$4737
$2400–$9500
Post-CHD with CABG, 1st year
$1300
$ 650–$2600
Post-CHD with CABG, subsequent years
$600
$ 300–$1200
Post-CHD without CABG, 1st year
$1500
$ 750–$3000
Post-CHD without CABG, subsequent years
$840
$ 420–$1700
3%
0%–7%
Annual treatment costs
24
Discount rate
BP indicates blood pressure; CHD, coronary heart disease.
able literature on South Africa. In general, the model was able
to accurately project the number of deaths due to ischemic
heart disease and stroke, the incidence of stroke, and the
overall direct cost of CVD. Our model predicted that 12% of
annual deaths for adults aged 35 to 74 years would be due to
ischemic heart disease and 14% would be due to stroke.
Published data on annual death rates due to ischemic heart
disease range from 5% to 13%, and annual death rates from
stroke range from 8% to 16% after adjustment for the more
than 20% of deaths that were unregistered or ill defined.31–33
Our model projected that the annual incidence of stroke was
323 per 100 000 persons. There are no published incidence
rates for stroke for the population as a whole, but Rosman34
found that the range was from 100 per 100 000 for those 20
years and older to 500 per 100 000 for those aged 55 years
and older. Our model results are well within these figures.
With regard to costs, our model also projected direct annual
CVD costs of US $690 million in 1991 costs. Pestana28 found
that direct CVD costs were estimated between US $620 and
$810 million in 1991.
TABLE 2.
Cost-Effectiveness
Model Predicted and Actual Outcomes
Outcome
Model Prediction
Published Reports, Range
Annual death rate due to
IHD, %
12
5–13
Annual death rate due to
stroke, %
14
8–16
Stroke rate, per 100 000
323
100–500
Annual direct cost of CVD,
$US millions
690
620–810
IHD indicates ischemic heart disease.
Table 3 displays the costs, life-years, QALYs, and incremental cost-effectiveness ratios for the 6 strategies of hypertension treatment compared with no pharmacological treatment
as a baseline. The 4 “absolute risk” strategies had incremental
cost-effectiveness ratios ranging from $700 per QALY
gained to $11 000 per QALY gained, depending on the risk
threshold for initiating treatment. The strategy of initiating
antihypertensive therapy for those individuals with a predicted 10-year CVD risk ⬎40% had an incremental costeffectiveness ratio of $700 per QALY gained compared with
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TABLE 3. Costs, Effects, and Incremental Cost-Effectiveness Ratios of Guidelines for Hypertension Management Over 10
Years in 10 Million Adults
Cost, $US Millions
Incremental
Cost,† $US
Millions
Effect, QALYs
(Millions)
䡠䡠䡠
8
78.185
78.173
Incremental
Effect,†
QALYs
Incremental C/E Ratio†
$/QALY
$/LYS*
䡠䡠䡠
12 000
䡠䡠䡠
700
䡠䡠䡠
900
No treatment
5820
Absolute risk CVD ⬎40%
5828
Absolute risk CVD ⬎30%
5874
46
78.214
29 000
1600
2100
Absolute risk CVD ⬎20%
6110
236
78.262
48 000
4900
6700
Absolute risk CVD ⬎15%
6351
241
78.284
22 000
11 000
18 000
1995 South African guidelines (target level
160/95 mm Hg)
6418
67
78.260
⫺24 000
Dominated‡
Dominated
Current guidelines (target level 140/90 mm Hg)
6735
317§
78.279
⫺5000
Dominated
Dominated
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LYS indicates life-years saved.
*Total and incremental life-years not shown.
†Each strategy’s cost and effect are compared with the preceding less costly one.
‡A dominated strategy is one that is both more expensive and less effective than the preceding strategy to which it is compared.
§Compared with absolute risk CVD ⬎15%, because the 1995 guidelines are dominated by the absolute risk CVD ⬎15% strategy.
no treatment. The absolute risk of CVD ⬎30%, absolute risk
of CVD ⬎20%, and absolute risk of CVD ⬎15% strategies
had cost-effectiveness ratios of $1600, $4900, and $11 000
per QALY, respectively, each being compared with the next
less inclusive treatment criterion. On the other hand, the 1995
South African guidelines and the 2001 South African Guidelines strategies were both more costly and resulted in fewer
gains in quality-adjusted life expectancy than the absolute
risk of CVD ⬎15% strategy and were thus dominated by the
less costly absolute risk treatment strategies in the costeffectiveness analysis. The overall rankings were unchanged
when outcomes were assessed in terms of years of life gained.
Sensitivity Analyses
Although there were some changes in the absolute values for
the incremental cost-effectiveness ratios over the range of
values tested, the only univariate sensitivity analysis that
altered the rank order of health benefits or costs of the drug
treatment strategies was the annual cost of hypertension
treatment (Figure 2). We varied the annual cost of hypertension from $43 to $192 to reflect a range from one half to 2
times our baseline assumption of $86. We found a threshold
point of $53 below which the absolute risk of CVD ⬎40%
strategy cost less and increased the number of life-years
gained compared with the “no-treatment” strategy. In this
high-risk population, the number needed to treat to prevent 1
event was low enough that below $53 per year of treatment,
the reduction in costs from preventing events was greater than
the cost of treating those who would not have an event over
the 10 years. Above $53 per year of antihypertensive therapy,
the ranking of the strategies was the same as in the base case,
Figure 2. Sensitivity analysis on cost of
hypertension treatment. One-way sensitivity analysis showing the impact of
varying the costs of hypertension treatment on the incremental costeffectiveness ratios of the guidelines that
were compared in this study. The 1996
South African guidelines and the JNC VI
guidelines are excluded because they
were dominated strategies. AR indicates
10-year absolute risk for CVD event.
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Figure 3. Sensitivity analysis on relative
risk reduction of coronary heart disease.
One-way sensitivity analysis showing the
impact of varying the relative risk reduction of treatment of hypertension compared with nontreatment on the incremental cost-effectiveness ratios of the
guidelines compared. The 1996 South
African guidelines and the JNC VI guidelines are excluded because they were
dominated strategies. AR indicates
10-year absolute risk for CVD event.
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with no treatment having the lowest costs and benefits and the
4 absolute risk strategies each with successive incremental
cost-effectiveness ratios. Furthermore, the incremental ratios
were quite sensitive to the increasing cost of hypertension
treatment. For example, the incremental cost-effectiveness
ratio for the absolute risk of CVD ⬎30% strategy ranged
from $300 to nearly $5000/QALY when the annual cost of
antihypertensive therapy was increased from $43 to $186.
Figure 3 displays that when the relative risk reduction of
coronary heart disease from hypertensive therapy was assessed over the range from 15% to 25%, the incremental
cost-effectiveness ratio increased inversely with the amount
of benefit of treatment. At an assumed reduction in coronary
heart disease events of 25% with treatment, the absolute risk
of CVD ⬎40% strategy had an incremental cost-effectiveness
ratio of $400/QALY, but with an assumed risk reduction of
15%, the ratio was $900/QALY. Plausible variations in each
of the other remaining variables listed in Table 1 did not
change the rank ordering of the strategies, and the costeffectiveness ratios never varied by more than 50% from the
base case. Furthermore, under the full range tested for each
variable in the univariate sensitivity analyses, the 1995 South
African guidelines and the JNC-VI– based guidelines remained dominated by the absolute risk threshold treatment
strategies.
The probabilistic multivariate sensitivity analysis using the
6 above-mentioned variables revealed little variation from the
base case and no change in the order of the strategies with any
of the iterations. For example, the mean incremental ratio
when we compared absolute risk of 30% versus 40% was
$1600/QALY, with 95% of the values within $200 of that
figure. The range was similar for each of the other comparisons having nondominated strategies, with 95% of the values
of incremental ratios varying by less than $200/QALY from
the base-case results.
Discussion
On the basis of the results of our population-based simulation
model, we conclude that for the current South African
population, hypertension guidelines based on an absolute risk
for cardiovascular disease are both more effective at saving
lives and less costly than those based predominantly on a
blood pressure level. This approach is even more attractive if
the cost of treatment could be reduced. We modeled the cost
of hypertension treatment based on the current mix of
medications used in South Africa. If the use of thiazides
replaces the more expensive calcium channel blockers or
ACE inhibitors, then the cost-effectiveness ratios for primary
prevention will be further reduced, and the absolute risk
strategies will be even more attractive, if not economically
dominant, compared with no treatment.
Furthermore, the conventional blood pressure– based
guidelines remained more costly and less effective with each
univariate and multivariate sensitivity analysis. We recognize
that our model is based on limited cost data, which is a
significant problem throughout the developing world. However, given that we applied the same costs of treatment to all
the intervention strategies, the result seen in the sensitivity
analysis still showed that the blood pressure level guidelines
were always dominated throughout the assessed ranges of
costs. Certainly, the costs of interventions could be much
lower if generic medications were used instead of the current
pattern of use of both patented and generic drugs in South
Africa. Thus, our estimates are likely conservative.
The choice of which absolute risk threshold might be
appropriate for South Africa can be guided by either a
comparison with what the country is currently doing or by
some other international standard. On the basis of our model,
switching from its current guidelines to one of treating those
with an absolute risk of CVD of ⬎15% could save the South
African society up to US $500 million over 10 years without
any decrement in the QALYs achieved under its current
guidelines. Alternatively, the Commission on Macroeconomics and Health recommended choosing interventions that
were less than 3 times the gross domestic product (GDP) per
capita. This figure would be $9000/QALY if we used the
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GDP figure ($3000/capita) from 2002 and would be consistent with the decision to treat all those at absolute risk of CVD
⬎20%. However, under this criterion, the absolute risk of
15% strategy would also be acceptable if a greater proportion
of generic medications, such as hydrochlorothiazide, were
used.
The use of absolute risk– based guidelines is relatively
new; however, guidelines that are based on absolute cardiovascular risk are more sensitive at predicting those at highest
risk. They have been shown in a model of coronary heart
disease in New Zealand to predict fewer cardiovascular
events than those based on a blood pressure level when
applied to people with the same risk factors.35 The present
findings are consistent with the WHO CHOICE by Murray et
al7: The absolute risk approach also had lower costeffectiveness ratios than the target-level approach. The present study extends their findings in 3 distinct ways. First, we
looked at a specific country with more detailed epidemiological and cost data. This allows an individual country like
South Africa to shift resources based on its specific health
needs and budgetary limitations. It allows a direct comparison
of the 2 possible approaches under consideration and evaluation of what a change from its current approach to a new one
might entail. Second, our model included inpatient costs of
CVD events. Given that these events are responsible for a
significant proportion of costs related to a blood pressure and
CVD prevention program, our costs more likely reflect actual
costs associated with the intervention. Finally, given that we
had specific country information, we were able to validate our
model.
Recent recommendations with regard to guidelines suggest
that they should be simple and easy for various types of
clinicians to follow.7 The exact risk of developing CVD can
be calculated with risk calculators found on a variety of
Internet Web sites. All that is needed is the specific risk factor
profile for the individual being evaluated, information that is
identical to what is needed to use the JNC VI guidelines.
Additionally, a recent study in a busy primary care setting in
the United Kingdom found that use of a chart based on
absolute risk calculations was well-liked, easy to use, and
resulted in a clinically significant reduction in blood pressure
compared with usual care.36
One limitation is that the absolute risk approach uses the
Framingham function, which is based on a predominantly US
white population. However, it has been shown to be equally
predictive among white and black men and women in the
United States.37 Furthermore, the case-control INTERHEART38 study confirmed that similar risk factors accounted
for the majority of myocardial infarction regardless of region.
Also, although many of our assumptions about risk assessment and treatment effects were based on Western data, the
model is validated well within the range of limited estimates
published on South Africa. Nonetheless, a cohort study
examining the CVD risk function in South Africans would
allow for refinement of our model and is an obvious area for
future exploration. Further generalization of our results to
other developing countries should take into account the fact
that the risk score may overestimate or underestimate disease,
CEA of Hypertension Guidelines in South Africa
3575
which would increase or decrease the incremental costeffectiveness ratios, respectively.
Acknowledgments
The first author would like to express gratitude to Eugene Braunwald
of Harvard Medical School for inspiration and his encouragement to
pursue this project at the Cape Heart Centre of the University of
Cape Town in South Africa as a Lancet International Fellow. Further
acknowledgement goes to Cynthia Young, research assistant, for
help in preparation of this manuscript.
The authors report no conflicts of interest.
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Cost-Effectiveness Analysis of Hypertension Guidelines in South Africa: Absolute Risk
Versus Blood Pressure Level
Thomas A. Gaziano, Krisela Steyn, David J. Cohen, Milton C. Weinstein and Lionel H. Opie
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Circulation. 2005;112:3569-3576
doi: 10.1161/CIRCULATIONAHA.105.535922
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