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Fig. 23.3 Quadrupole
time-of-ight mass
spectrometry (QTOF-MS)
schematic. The red arrows
track the movement of the
analyte/ion path
D. Lane et al.
high sensitivity of MS platforms, <1% renally excreted compounds may still be detected.
Clinical Workow forChemical Testing
CAT workows are similar to precision medicine. The cyclical nature of testing and speaking with a patient with apparent resistant hypertension may be characterised in the
following:
• Patient with apparent resistant hypertension provides a
sample after they are asked about adherence and habits
• The sample is sent to a centralised laboratory for
analysis
• The results are conrmed and authorised by the laboratory/pathology team
• On the next visit, the results are shared in an open, nonjudgemental discussion
• Management plan is made, the above steps are repeated
where necessary
Often, in the case of a non-adherent result, merely providing
evidence of non-adherence is enough to open a new and honest dialogue that would otherwise not be attainable.
Contributors to non-adherence may be discussed to identify
the cause, and a new management plan can be considered.
For example, where polypharmacy has been outlined (and
where all medications returned a negative result i.e., not
detected in urine/blood), the number of prescriptions could
be reduced to ease the burden and increase the likelihood of
adherence—though due caution must be taken, where nega-
tive results may have been skewed by differing patient pharmacokinetics. Direct observed therapy may be necessary to
rule out these limitations. The use of single pill combination
to simplify treatment schemes is recommended to address
this issue [3].
Similarly, if forgetfulness is the issue, reminder alarms,
involving a family member in providing medications, can be
addressed. A discussion can also ascertain patients understanding of their condition. It provides the opportunity to
correct false believes about medications, concerns about
toxicity.
For those with adherent results (i.e., medications detected
in blood/urine), resistant hypertension may be the diagnosis.
However, adherence is not a static construct and is variable
over time. The patient may have simply taken their medications just prior to the clinic visit (‘white coat adherence’).
Measuring BP before sampling urine/blood may help to confound this. Still, it is important to also emphasise positive
feedback to the patient where the result is positive.
Drug Adherence andRenal Denervation
inHypertension
When BP control is not attained despite multiple antihypertensives or patients do not tolerate drugs or do not wish to
take drugs for a lifetime, interventional procedures to manage hypertension have emerged, the most prominent one
being renal denervation (RDN) [21]. The main idea of this
approach is that BP could be controlled with no or a limited
number of antihypertensive drugs, thereby limiting the clinical impact of a poor adherence. The BP response rate of
23 Drug Adherence inHypertension Management
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233
RDN is similar to the efcacy of a single antihypertensive
agent, e.g., −5 to −7mm Hg systolic BP and is totally independent of the drug adherence level prior to the intervention
[22].
From 9 long-term (>12months), follow up renal denervation studies (as outlined by Liang etal. (2021) [23], medication
changes were largely unchanged after the follow- up as illustrated in Table23.1. Krum etal. (2009) found no change in the
number of drugs after RDN (though their protocol asked medication changes to be limited where necessary) [24]; EnligHTN
I decreased (4.24–4.16 medications per patient) [25]; Simplicity
HTN-1 increased (5.1–5.6) [26]; Simplicity HTN-2 decreased
(5.1–4.6) [27]; RAPID did not stipulate 12-month data [28]. In
SYMPLICITY HTN-3 the number of pills only slightly
changed at 6months (5.0–5.1), and we do not have follow-up
data [29]. In REDUCE-HTN the number of pills per day did
not signicantly change (raw data not reported) [30]. In
EnligHTN III a net decrease was mentioned but raw data were
not reported [31] and in the Global SYMPLICITY Registry a
very small decrease (4.5–4.4) was observed [32].
In the short-term follow-ups (6 months) of note, the
ENCOReD study saw prescriptions reduced from 4.7 to 4.4
[33]. In the RADIANCE-HTN SOLO trial, the percentage of
patients receiving antihypertensive medications 2 months
after the intervention were 48% in the renal denervation
group and 61% in the control group (p value non-signicant)
[34]. In the more recent SPYRAL HTN-ON MED proof-ofconcept randomised trial, adherence to antihypertensive
drugs was 65.8% at baseline and 60.5% at 6months with no
difference between the renal denervation and the control
group [35]. In the RADIANCE-HTN TRIO, the number of
patients receiving additional antihypertensive medications
after the 2-month measurement of ambulatory BP and
patients with reduction in antihypertensive medications did
not differ signicantly between RDN and controls although
a slight trend was observed in favour of RDN. The
Table 23.1 Changes to antihypertensive medication after renal denervation intervention from long-term follow-up trials. Only studies
including numeric data (not percentage) have been included
Baseline
Long-term renal
denervation studies
EnligHTN I (2014) 4.24 4.16 (12-months)
Simplicity HTN-1
a
(2014)
Simplicity HTN-2
b
(2014)
Simplicity HTN-3
(2014)
Global SYMPLICITY
Registry (2019)
a
Prescription changes were discouraged until 12-months
b
Prescription changes were discouraged until 6-months
prescriptions
(mean)
5.10 5.60 (36-months)
4.60 5.10 (36-months)
5.10 5.00 (6months)
4.50 4.40 (12-months)
Follow-up
prescriptions (mean,
months)
RADIANCE-HTN TRIO trial will publish further follow-up
data soon (as of the time of writing, circa 2021-end) [36].
The main point here is that adherence will still be relevant
even after interventions such as RDN as the majority of
patients with resistant hypertension that are treated with
RDN require either the continuation or the prescription of
drug therapies to control BP.Research has shown adherence
is still a problem for these patients [22].
Few RDN studies monitored adherence during the study
period, and often adherence was only screened (using subjective methods) prior to commencing the trial. Patel etal.
(2016) used CAT to show that 23.5% of patients referred for
the procedure were not taking their medications in the rst
instance [7]. In the recently published RADIANCE-HTN
TRIO a randomised, multicentre, single-blind, shamcontrolled trial, full adherence to the combination medications remained high at 2months among patients (by CAT),
with no difference between the renal denervation and sham
groups (42 [82%] of 51 vs 47 [82%] of 57) [36]. The power
of confounding adherence by objective measures in studies
like those is still a pertinent topic, especially as RDN gains
traction once again. This, along with other confounding
issues (e.g., poor trial design, heterogeneity between interventions etc.), have likely contributed to the slow and cautious interest of RDN in resistant hypertension.
Issues andFuture Research
Though CAT is increasingly considered the recommended
approach in clinical practice, the test still has a couple of
important problems. Firstly, as before, variable pharmacokinetics– how the body moves the medication around and to
what degree it is excreted– may contribute to false negative
results. Some patients have polymorphisms in cytochrome
P450 enzymes, which affect both metabolism and drug transportation. These polymorphisms modify the clearance rates
and thus the amount that is excreted at a given moment. If the
medication is not cleared normally, the amount in the tested
biomatrix may be below the assays limit of detection. Studies
are needed to establish pharmacokinetic models in hypertensive patients. Secondly, there is a debate on which biomatrix
to collect for testing. Urine offers ease and is non-invasive to
collect surplus amounts. Blood derivatives overcome issues
where medications are not excreted by the renal route, though
sampling is more invasive. Either may be used, however.
Thirdly, the “tooth-brush” or “white coat adherence” effect
may skew true ndings and lack of information on the dosing
history may limit the global interpretation of the data.
Therefore, the context of the result should always be noted
(for example, is the patient achieving BP targets?) and mea-
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D. Lane et al.
surements might be repeated during the course of therapy.
Further issues include the limited use of CAT in the US (as
insurance may not cover the test), and in randomised controlled trials are needed to consolidate its usefulness.
Teaching and training guidance will need to be provided to
allow homogenous application of CAT. There are other
issues that mostly pertain to variances in detectable medication (e.g., sampling time).
As the technology develops, the outstanding issues will
most likely be ironed out. It is hoped that in near future these
CAT may be able to give insight to dosing habits or they might
be combined with other technologies. They may also be used
outside of gauging adherence. For example, up-titrating antihypertensive dose given a lower than usual amount found in
blood (i.e., therapeutic drug monitroing). With precision medicine rapidly evolving, these approaches are likely. Currently,
38% of ESH Excellence centres use CAT [37]. This number
will likely increase given a soon-to- be published manuscript
(circa., Dec 2021) providing recommendations and guidance
on adherence testing has been endorsed by the European
Society of Hypertension (ESH) Working Group on
Cardiovascular Pharmacotherapy and Adherence [38].
Finally, there is a need to educate health care professionals on the assessment of non-adherence and, more importantly, on how to discuss this with patients. There are some
initiatives being undertaken by the ESH in this area.
Acknowledgments None.
Sources of Funding L is supported by the National Institute
for Health Research (NIHR) Applied Research Collaboration
East Midlands (ARC EM). The views expressed in this publication are those of the author(s) and not necessarily those
of the National Institute for Health Research or the
Department of Health and Social Care.
Disclosures None.
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Patient Preference forTherapies
https://t.me/medicina_free
inHypertension
FilipM.Szymanski andAnnaE.Platek
24
The physician’s instrumental communication behavior, such
as obtaining and providing information, accounts for 60% of
interactions with the patient, 23% of which are dedicated to
patient questions [1]. Many patients believe that doctors
spend too little time informing the patient about the medical
condition and treatment options and patient preference is
often not explored or taken into consideration.
The approach to medical care has changed signicantly
over the centuries. In the last decades doctors’ approaches to
patients have changed. In previous centuries the main focus
was the biomedical aspect of a disease with less attention to
the impact of mental factors on health. A breakthrough that
changed this concept was the new denition of health developed by the World Health Organization in 1946. It dened
health not only as the absence of disease but also as a full
physical, mental and social well-being. It promoted a return
to approaching health and illness in the Hippocratic fashion,
and the patient was approached holistically again. Another
pivotal moment was introducing the term ‘patientcenteredness’ by Balint, who suggested that each patient
“has to be understood as a unique human being” [2]. Among
many others, those moments laid a foundation for a humanistic approach to medical care and medicine we know today.
Much time had to pass before the patient became a subject
rather than an object of the treatment. Patient-centeredness
was dened as “providing care that is respectful of and
responsive to individual patient preferences, needs, and values” [3]. Patient preference became a concept in outcomes
research, medical product development and has been incorporated into several clinical practice guidelines.
Unfortunately, research on patient preference is still
insufcient, and there is much heterogenicity in outcomes
studies across the literature. This may be because patient
F. M. Szymanski (*)
Cardinal Stefan Wyszynski University in Warsaw, Warsaw, Poland
A. E. Platek
Cardinal Stefan Wyszynski University in Warsaw, Warsaw, Poland
Medical University of Warsaw, Warsaw, Poland
preference is dependent on a milieu of factors and is not easily measurable [4].
Importantly, patient preference affects several aspects of
treatment. It seems that it plays a crucial role in chronic disease treatment, including hypertension. Lifelong effective
treatment of hypertension, especially non- or mildly symptomatic, requires a high level of determination and doctorpatient cooperation. Therefore, patient preference regarding
which antihypertensive strategy should be used is currently
extensively studied.
A primary component upon which adherence to a particular treatment depends upon is patient preference.
Review of the literature shows that several factors play a
crucial role in adherence: schedules, type and efcacy of
pharmacotherapy [5]. It was shown that, in general,
patients prefer more effective over safer medications.
Factors responsible for changes in long-term adherence to a
therapy include dosing and costs.
It has also been reported that, in patients taking cardiovascular medications, dosing schedule not corresponding with
patient preference negatively affects adherence [6]. One in
four patients reported being inconvenienced by their drug
dosing schedule, and these subjects were less adherent
(46.2% vs 16.7%) to their drug regimen than those who did
not report inconvenience. Taking into consideration preference regarding the preferred medication schedule could signicantly improve adherence.
Patients’ Preference inHypertension
Treatment
A pivotal aspect that improves patients’ involvement in therapy is education. Even simple aspects such as medication list
composition are relevant and may play a role in patients’ attitude towards treatment. A study of patients taking eight or
more medications, aimed to identify medication-list components preferred by patients [7]. It showed that patients prefer
a more elaborate list, including dosing, timing, the onset of
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
R. R. Heuser et al. (eds.), Renal Denervation, https://doi.org/10.1007/978-3-031-38934-4_24
237
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F. M. Szymanski and A. E. Platek
treatment and reason for the medication. More importantly,
the survey showed that 22.7% of patients did not know the
names of all the medications they were taking; 13.2% did not
know the medical problems for which they were taking their
medications and 30.2% did not know the dosages of the
medications. Nevertheless, 96.2% felt that they took an
active part in their medical care. It shows that patients feel a
need for active participation despite problems in understanding provided information.
One of the more important studies on patient preferences
towards hypertension management was conducted in the
United Kingdom as an unlabeled discrete choice experiment
(DCE) [8]. In a DCE participants are presented with questions asking to choose between hypothetical alternatives. In
the described study, participants were aged 50–86years and
73% had been diagnosed with hypertension for >5 years.
They were interviewed to help establish their preferences
regarding hypertension management based on four factors: a
model of care, frequency of blood pressure measurements,
reduction in 5-year cardiovascular risk, and costs to the
National Health Service. With respect to the model of care
domain, patients preferred treatment guided by a doctor over
pharmacist, telehealth or self–management. As for the frequency of blood pressure measurements, patients preferred
more frequent measurements over those conducted twice or
once a year. The most signicant factor inuencing patients’
preference towards treatment was the predicted reduction in
5-year cardiovascular risk. Scenario analysis showed that
when the outcome changed from lowest to highest risk reduction category, the likelihood that participants would choose a
model of care doubled. Patients preferred therapies with a
higher risk reduction level and were willing to pay more for
those kinds of treatment (annually £374.74, £398.98, and
£673.45 for 10%, 15%, and 25% reduction in 5-year cardiovascular disease risk, respectively). In summary, the study
showed that when offering new models of care, it is essential
to discuss the outcomes in terms of risk and risk reduction,
which may impact the ‘buy-in” among patients.
In a survey assessing the impact of patient preference on
the initiation of treatment, a group of 52 hypertensive participants was evaluated [9]. The study showed that 56% of patients
informed about their condition preferred treatment with hypertensive medications rather than no treatment. Moreover, there
was a substantial disagreement between the patient decision
and the actual initiation of the pharmacotherapy.
In another study conducted in Germany, classical pharmacotherapy methods were compared with catheter-based
renal denervation (RDN) [10]. The study included patients
with stage 1 or stage 2 hypertension treated in outpatient settings. A questionnaire-based cross-sectional survey collected
information on demographics, duration of hypertension,
antihypertensive medication duration, medication (how
many pills and side effects), willingness to receive alterna-
tive treatment with catheter-based RDN, and determinants
for the choice of their decision. A total of 1011 patients at a
mean age of 66years completed the survey. The mean duration of hypertension and time on hypotensive treatment was
10.8 and 10.2years, respectively. In the previously untreated
patients, 61.7% of survey participants would prefer tablets
and 38.2% would opt for a one-time RDN procedure. Of the
entire study population, between 36.3% and 39% opted for
RDN, with patients <50years being slightly more open for
this treatment method. When patients were asked what type
of second-line therapy would they prefer in case of pharmacotherapy inefcacy, 71.8% would instead take an additional
pill, while 28.2% would opt for RDN.
In summary, the study showed that a considerable fraction
of hypertensive patients would choose RDN over or in addition to lifelong pharmacotherapy provided that they would
benet from a signicant decrease in blood pressure. Patients
preferring this treatment option were younger and more
likely to be male than those preferring pharmacotherapy.
An impact of patients’ preference was also studied in
pregnancy-related hypertension [11]. The study included
183 pregnant women, of whom one-third reported past pregnancy hypertension and one-quarter reported current pregnancy hypertension. All patient completed a questionnaire
developed to determine women’s preference for tight or
less- tight control of blood pressure, how they may prioritise
potential treatment components (in example taking medication) and adverse outcomes as part of their decision-making,
and how they would like to be supported in their decisions.
Based on the answers patients were divided into three
groups: /1/ “early delivery avoiders” (23% of respondents),
who prioritised reducing the risk of preterm delivery, /2/
“medication minimisers” (14% of respondents) who prioritised reducing the likelihood of taking medication and /3/
“equal prioritisers” (62% of respondents) who assigned
roughly equal priority to all aspects and benets of treatment. Diverse decisional needs were expressed across the
population, but most women preferred to make nal treatment decisions themselves (70%), 48% of which with doctor’s input.
Patients’ Preference inCardiovascular
Prevention andChronic Disease Treatment
The main goal of the treatment of elevated blood pressure is
lowering cardiovascular morbidity and mortality. Therefore,
an essential aspect of the approach focused on patient preference towards treatment should also include cardiovascular
prevention and risk reduction. A recent metanalysis aimed to
review current evidence regarding the minimum acceptable
risk reduction of a cardiovascular event than patients feel
would justify the daily intake of preventive medication [12].
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239
The metanalysis included 22 studies, involving a total of
17,751 participants. The outcomes of screened treatment
methods communicated to the patients in six studies were
prolongation of life, in 12 studies- absolute risk reduction
and in 14 studies number needed to treat. In the prolongation
of life studies, it was shown that a mean of 48% participants
would consider taking a medication if it prolonged life by
<8months and a mean 64% if it prolonged life by ≥8months.
In studies framed using absolute risk reduction, an average
of 54% participants would consider taking a medication that
reduces their 5-year cardiovascular disease risk by <3%, and
an average of 77% would consider it if it reduces their 5-year
CVD risk by ≥3%. In studies using a 5-year number needed
to treat an average of 60% participants would consider taking
a medication with a number needed to treat>30 and an average of 71% with the number of ≤30. The study showed the
importance of communicating potential benets in cardiovascular morbidity and mortality risk reduction. Even a
slight reduction in cardiovascular risk was sufcient to convince a majority of patients to treatment. However, the willingness for preventive pharmacotherapy is also dependent on
the form and cost of treatment. In one study discrete choice
survey was presented to patients to assess the inuence of
polypill-based treatment attributes on preferences for cardiovascular preventive treatment [13]. Attributes included outof- pocket costs, tablet number, administration, and prescriber
visit frequency. The survey involved choices between two
hypothetical treatment options and no treatment for CVD
prevention. It showed that a vast majority of patients (93%)
chose active treatment, compared with no treatment.
Willingness for treatment decreased signicantly with
increasing out-of-pocket cost and tablet number. It shows
that xed-dose combinations and invasive treatment could be
a feasible option in cardiovascular preventive treatment.
Moreover, in chronically ill patients, an approach to
aggressive medical therapies with potentially stronger
adverse reaction varies signicantly and should be left to a
patient decision. Preferences for aggressive medication therapies may differ between patients and health care providers.
A recent study [14] showed that approximately 40% chose
aggressive medication therapy, even when facing potentially
stronger adverse reactions. The study also showed that
healthcare providers’ general ability to predict patients’
choice is generally low. Therefore, all treatment options
should be presented to patients regardless of doctors beliefs.
focused on patient preference, self-management, and
improving health literacy to obtain better disease control [15,
16]. Moreover, respecting patient wishes when choosing
treatment strategy varies between different scientic societies. In the 2018 European Society of Cardiology guidelines
for the management of arterial hypertension, the term
“patient preference“is almost entirely omitted [17]. It is
addressed only in the section referring to the management of
poor adherence as follows “Barriers to optimal adherence
may be linked with physician attitudes, patient beliefs and
behaviour, the complexity and tolerability of drug therapies,
the healthcare system, and several other factors.
Individualised solutions should be found.” The 2020
International Society of Hypertension Global Hypertension
Practice Guidelines also does not mention the role of patient
preference in choosing the antihypertensive treatment strategy [18].
An entirely different approach is promoted in the
American Heart Association Guidelines. In 2017 hypertension guidelines and 2019 primary prevention guidelines, it is
rmly stated that consideration must also be given to preference, personal beliefs, values, and culture when choosing the
treatment strategy [19, 20]. The patient’s involvement in the
decision-making process aims to increase the adherence to
recommendations.
In the forthcoming years, the impact of patient preference
on everyday practice will gradually increase and have a more
signicant impact on guideline recommendations and clinical practice.
Conclusions
In summary, current medical practice shifts towards a
patient-centred approach that incorporates current medical
knowledge and an individual’s preferences and beliefs. The
ultimate goal of this approach is to maximise treatment benets, while optimising adherence, minimising adverse reactions rendering the treatment as little burdensome as possible.
The same principles apply to the treatment of hypertension
as any other chronic disease. Also, a decision to initiate,
titrate or withhold a treatment should be made following
patient preference. This is very important today in the presence of many, including several invasive, treatment
strategies.
Guidelines-Based Approach toPatient
Preference
A gradual change has been noted in the approach to patient
preference in guidelines. As in the treatment of other chronic
diseases, the management model is moving to be more
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HYP.0000000000000065.
Renal Denervation Cost Analysis
https://t.me/medicina_free
andConsideration
JulieBulsei andIsabelleDurand-Zaleski
25
Background
According to the World Health Organization (WHO), hypertension ranks second, after tobacco, on the list of factors that
reduce the number of healthy life years [1]. Treating high
blood pressure (BP) is therefore essential, especially as the
introduction of an antihypertensive drug treatment signicantly reduces cardiovascular (CV) complications associated
with hypertension. However, between 5% and 30% of the
total hypertensive population cannot control their BP despite
drug treatment [2, 3]. These resistant hypertensive patients
are then exposed prematurely to a high CV risk leading to a
heavy economic burden on the society. Indeed, in addition to
the direct costs associated with healthcare utilization (medical consultations, hospitalizations, drug treatments...),
uncontrolled hypertension is associated with substantial productivity losses resulting from disability and premature mortality [4]. It is therefore essential to nd effective treatments
to control resistant high BP [5].
Renal denervation (RDN) is an innovative treatment for
patients with resistant hypertension. In contrast to the low
cost of antihypertensive drug treatment (about €30 per
month), RDN cost amounts to approximately €8000 depending on the country [6]. However, RDN could lead to a signicant and long-term drop in BP and therefore could
signicantly reduce CV complications and their associated
costs, knowing that CV diseases make up around 10% of
total health expenditure in developed countries.
Each year, like RDN, a large number of innovative strategies arrive on the healthcare market. In a context of limited
available nancial resources, healthcare authorities have to
decide whether or not the innovative strategy should be
adopted. Economic evaluation, examining both the costs and
effectiveness of the strategies being compared, will help in
the decision-making process.
General Scope
The objectives of this chapter are rst to highlight debates
about interventional treatments of hypertension, and in particular RDN, which involve cost issues and secondly to
help clinicians in their critical appraisal of journal articles
that present economic evaluations. It is not to present an
exhaustive discussion of the several hundred articles
indexed in Medline that deal with interventional treatments
of hypertension and costs, nor to discuss the many reviews
on that same topic.
Economic Evaluation andPolicy Decisions
This chapter is derived, in part, from an article published in Blood
Pressure on October 26, 2017, available online: https://www.tandfon-
line.com/doi/full/10.1080/08037051.2017.1394160?scroll=top&need
Access=true [Article DOI https://doi.org/10.1080/08037051.2017.139
4160]. Permission has been received for this material to be
reproduced.
J. Bulsei (*)
DRCI, Délégation de la recherche clinique et de l’innovation, CHU
de Nice, Université Côte d’Azur, Nice, France
e-mail: bulsei.j@chu-nice.fr
I. Durand-Zaleski
URC Eco IdF, Unité de recherche clinique en économie de la santé
d’Ile de France, AP-HP, Paris, France
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
R. R. Heuser et al. (eds.), Renal Denervation, https://doi.org/10.1007/978-3-031-38934-4_25
Why is economic evaluation an important component of
health technology assessment and of its current sequel, comparative effectiveness research? Economic evaluations, in
addition to effectiveness measures, are necessary to ensure
that resources are allocated where they produce the greatest
health benet. But the comparison of medical strategies that
both use different resources and yield different outcomes
requires a specic approach.
Economic evaluation is currently both a decision-making
tool and an evolving academic discipline. Its general purpose
is to relate the costs of a diagnostic or therapeutic strategy to
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Cost difference(€)
Reduction in systolic blood pressure (MmHg)
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J. Bulsei and I. Durand-Zaleski
its outcomes. Thus, the two components of the evaluation are
a measure of effectiveness and an estimate of costs.
Costs and health outcomes of each alternative strategy are
compared using an incremental cost-effectiveness ratio, the
ICER. This ratio, calculated as the incremental change in
costs divided by the incremental change in health outcome,
represents the cost for one additional unit of health outcome
and is the main result of the economic evaluation. A positive
result means that the increase in costs results in a better medical outcome. The lower the cost-effectiveness ratio, the
more efcient the strategy is [7–11].
The costs of each alternative strategy are expressed in
monetary terms, while health outcome is expressed in a single medical unit, for example lives saved, life expectancy,
quality-adjusted life-year (QALY) or the reduction of BP or
CV events for hypertensive patients.
The increasing use of the randomised controlled trial as a
vehicle for economic evaluation presents the opportunity to
sample economic as well as clinical data and offers the
potential for uncertainty to be quantied through conventional statistical techniques [12]. It is now common for economic evaluations of antihypertensive treatments to use the
more sophisticated representation of uncertainty, which is
based on bootstrap replications and shows 1000 results
obtained by tacking one random cost outcome dividing it by
one random effectiveness outcome. The set of these estimated ICERs is presented as a scatterplot of 1000 points on
a cost-effectiveness plane. As described in the Bulsei etal.
article [6], “The percentage of ICERs in each part of the
cost-effectiveness plane is then presented in order to know
where the innovative strategy is mostly located compared to
the reference. If the new strategy is dominated (in the top
left-hand quadrant) it will be rejected and on the contrary, if
it is dominant (in the bottom right-hand quadrant) it will be
accepted by the public decision-maker. If the new strategy is
located in the top right-hand quadrant or in the bottom lefthand quadrant, indicating respectively a higher cost for
greater effectiveness or a lower cost for lower effectiveness,
a willingness to pay (WTP) threshold will have to be set by
the public decision-maker [9, 10].”.
Figure 25.1 presents the cost-effectiveness plan of the
French DENER-HTN study, which assesses the impact of
RDN in terms of cost and effectiveness (reduction in systolic
BP) compared to the reference drug treatment. 94% of the
replications are in the top right-hand quadrant, indicating a
higher cost for greater effectiveness of RDN [6]. The public
decision-maker must then set a WTP threshold in order to
decide whether or not RDN should be adopted.
As described in the Bulsei etal. article [6], “The WTP
threshold corresponds to a maximum monetary value that a
decision-maker might be willing to pay for a unit change in
outcome and can be visualized on a cost-effectiveness
acceptability curve that is derived from the bootstrap. The
acceptability curve shows the probability that the treatment
is cost-effective compared with the alternative according to
the value of the threshold [13].” For example, Fig. 25.2
shows the acceptability curve of the DENER-HTN study. At
a threshold of €1500/mmHg reduction in systolic BP, there is
50% chance that RDN is cost-effective and at a threshold of
€4000/mmHg reduction in systolic BP, there is 90% chance
that RDN is cost-effective [6].
Some countries have set an explicit threshold, others not.
The World Health Organization (WHO) suggested that this
threshold be based on the per capita national gross domestic
Fig. 25.1 Scatter plot of
incremental cost and
effectiveness of RDN
compared to the reference
drug treatment at 6months
[6]
13000
11000
9000
7000
5000
3000
1000
-1000
-3000
-5000
-10
-8
-6 -4 -2
WTP threshold ?
0
2
4
68
10
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