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1
Probability cost-effective
Willingness to pay ( ) per reduction in systolic blood pressure
0
25 Renal Denervation Cost Analysis andConsideration
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Fig. 25.2 Cost-effectiveness
acceptability curve showing
the probability that RDN is
cost-effective compared to the
reference drug treatment at
6months [6]
243
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
0 1000
product (GDP). An innovative strategy is considered costeffective with a threshold of 3 times the GDP per capita, and
2000 3000 4000 5000 6000 7000 800
regression of cardiovascular risk than the one that can be
theoretically estimated by risk scores or equations.
very cost-effective with a threshold of one time the GDP per
capita. In the UK, the threshold usually mentioned is GBP
20,000– GBP 50,000 per QALY depending on the argumentation. In France, the health authorities have not specied the
WTP threshold and the decision to adopt an innovative strategy is taken on a case-by-case basis [14]. These thresholds
are usually xed in cost per QALY.While, as the example of
the DENER-HNT study, another medical unit may be used
for the health outcome, such as reduction of BP or CV events
for hypertensive patients. Comparison of the economic study
result with the international literature using the same clinical
criterion can then help health authorities make a decision.
In the international literature, there are few cost- effectiveness
studies on RDN.Most of them used a model (Markov model
or decision tree) to assess the long-term impact of RDN in
terms of cost and effectiveness compared to antihypertensive
medical treatment. These studies concluded on the costeffectiveness of RDN, but the ICER varies signicantly
depending on the country and the input data [15–20].
For example, the German model based on SIMPLICITY
HTN-2 results predicted a relative risk reduction of 0.7–0.8
corresponding to a reduction of 32mmHg in systolic BP.The
estimated ICER was then very good (€2500/QALY) with 97%
of the bootstrap replications below the WTP threshold of
€25,000/QALY [15]. Most of the other published economic
Renal Denervation Economic Evaluation
models are based on the same SIMPLICITY HTN-2 results,
which are much more favourable than SIMPLICITY HTN-3
Lower blood pressure has a positive impact on the long-term
CV morbidity and/or mortality, so to be relevant the time
horizon of RDN economic evaluations must be over several
years and ideally over a lifetime. However, since the longterm effectiveness of RDN is as yet unknown, assumptions
have to be made in order to extrapolate the results of clinical
studies over a longer time horizon. The assumptions that
need to be made concern:
results. An Australian study used SIMPLICITY HTN-3 results
but only on the population under 65years of age, which was
the only population for which the study demonstrated an effective reduction in BP (5.7mmHg). The estimated ICER was
then €32,503/QALY, which is higher than the German study
but still cost-effective (less than one time the Australian GDP
per capita) [20]. Finally, the French DENER-HTN study has
used clinical data prospectively collected from an open-label,
randomized controlled trial with blind endpoint evaluation to
• The sustainability of the long-term benet given a possible loss of adherence to treatment, as current clinical studies have a relatively short follow-up period (6months);
• The linear reversibility of the cardiovascular risk: risk
models are used to estimate the increased risk of CV
events given increased BP, but it is likely that BP reduction induced by treatment produces a lesser degree of
estimate the ICER.The 6-month ICER was €1450 / mmHg
reduction in systolic BP and the ten-year ICERs were
€1,375,304/cardiovascular death avoided and €408,021 /
patient avoiding cardiovascular event(s). These results cannot
be compared to institutional WTP thresholds, but healthcare
authorities will be able to use the ICER as well as the bootstrap
and acceptability curve for decision support [6].
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J. Bulsei and I. Durand-Zaleski
The major limitation of these economic studies is that
long-term effectiveness of RDN is only an assumption not
yet demonstrated. This is why these studies had to estimate
the risk of CV events from risk scores or risk equations, and
are therefore likely to overestimate the benets of
RDN. Moreover, these studies are based on the positive
results of small-scale clinical trials (i.e. SIMPLICITY HTN2, DENER-HTN) or of patients’ sub-category from larger
studies (i.e. SIMPLICITY HTN-3) and not on the nonsignicant reduction of systolic BP at 6 months of the
SYMPLICITY HTN-3 study. Readers should therefore be
cautious about these results.
The arrival in the US and Europe of new RDN technolo-
gies (allowing a deeper and less variable ablation), followed
by new studies based on a better methodology, should help
the health authorities to redene the place given by health
authorities to RDN in the therapeutic arsenal of resistant
hypertension.
Renal Denervation Alternatives
andEconomic Evaluation
Currently the only therapeutic alternative to RDN is the addition of antihypertensive drugs with dose titration. With this
therapeutic approach, the BP reduction remains incomplete
and the patient is potentially exposed to an increased risk of
side effects and non-compliance [21, 22]. Unilateral carotid
baroreceptor stimulation also appears to be an innovative
alternative [23]. The use of a decision analytic model to
assess the impact of barostimulation in terms of cost and
effectiveness compared to antihypertensive medical treatment has showed very different ICER depending on the
country (€58,000/QALY in the US and €8000/QALY in
Germany) [24, 25]. The baroreceptor stimulation procedure
is currently being evaluated in France in a prospective randomized controlled trial and the cost-effectiveness will be
assessed [26, 27].
Perspective
Any chapter on health economics would be incomplete if it
left the reader with the impression that policy decisions
result directly from the calculations described above. A
framework for the analysis of how policymakers use the
information is provided by M Goddard etal. in their article
on priority setting in health [28]. The world of healthcare
delivery is not limited to clinicians and economists, other
stakeholders such as politicians, bureaucrats, taxpayers,
interest groups and the industry are involved. Public and professional institutions seek to maximise their power and inuence in the healthcare sector and policymakers seek to
maximise their political support. Consumers (patients) are
outcome maximising and healthcare providers (in the private
sector) are prot maximising. With this in mind, the processes of organisation and delivery of health services and
technologies appear more complex than a straightforward
application of the results of economic evaluations would
suggest.
Conclusion
RDN appears to be more effective but also more expensive than the reference antihypertensive treatment.
However, as short-term effectiveness has not been shown
in all clinical studies and long-term effectiveness is only
an assumption not yet demonstrated, readers should be
cautious about the results of the current economic studies. The arrival of new devices, followed by new studies,
should help the health authorities to decide on the adoption or not of RDN in the therapeutic arsenal of resistant
hypertension.
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pdf/2014- 12/valeurs_de_reference_vf.pdf
15. Geisler BP, Egan BM, Cohen JT, Garner AM, Akehurst RL, Esler
MD, etal. Cost-effectiveness and clinical effectiveness of catheterbased renal denervation for resistant hypertension. J Am Coll
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16. Dorenkamp M, Bonaventura K, Leber AW, Boldt J, Sohns C, Boldt
L-H, et al. Potential lifetime cost-effectiveness of catheter-based
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ML, Kofjberg H.Cost-effectiveness of renal denervation therapy
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19. Tilden D, McBride M, Whitbourn R, Krum H, Walton T, Gillespie
J.Cost effectiveness of catheter-based renal denervation for treatment resistant hypertension—an Australian payer perspective.
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20. Chowdhury EK, Reid CM, Zomer E, Kelly DJ, Liew D.Costeffectiveness of renal denervation therapy for treatmentresistant hypertension: a best case scenario. Am J Hypertens.
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25. Borisenko O, Beige J, Lovett EG, Hoppe UC, Bjessmo S.Costeffectiveness of Barostim therapy for the treatment of resistant
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26. Rossignol P. Carotid barostimulation in the treatment of resistant
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27. Rossignol P, Massy ZA, Azizi M, Bakris G, Ritz E, Covic A, etal.
The double challenge of resistant hypertension and chronic kidney
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health—a political economy perspective. Health Econ Policy Law.
2006;1:79–90.
What Needs toBeShown Before Renal
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Denervation Can BeUsed inClinical
Practice?
ManishSaxena andMelvinD.Lobo
26
Abbreviations
ABP Ambulatory blood pressure
CTA Computed tomography angiography
eGFR e-glomerular ltration rate
FDA Unites States Food and Drug Administration
HTN Hypertension
MRA Magnetic resonance angiography
NICE The National Institute for Health and Care
Excellence
SNS Sympathetic Nervous System
US Ultrasound
RF Radio frequency
Introduction
Results from recent randomised, blinded, sham-controlled
studies have re-established RDN as a promising devicebased therapy for HTN targeting sympatho-modulation
through renal nerve ablation [1–5][previously reviewed in
Chap. 10]. Data from these studies has contributed to bringing radiofrequency (RF) and ultrasonic (US) RDN technologies closer to market authorisation with regulatory bodies to
become licensed treatments for HTN.
However, there are still some apprehensions in the clinical community about the potential use of RDN (at very high
cost compared to drug therapy) as a treatment option for
HTN in routine clinical practice. This is due to existing evidence gaps with current studies that need addressing to
enable the clinical community to feel more condent and
reassured about the benets of recommending RDN as a
M. Saxena (*) · M. D. Lobo
Barts NIHR Cardiovascular Biomedical Research Centre,
Charterhouse Square, William Harvey Research Institute, Queen
Mary University London, London, UK
e-mail: m.saxena@qmul.ac.uk; m.d.lobo@qmul.ac.uk
potential treatment option for hypertensive patients. Also, as
RDN moves closer towards clinical adoption, the requirements for clinical commissioning of these therapies in state
funded health economies remains unclear.
Here we discuss evidence gaps from current data with
ongoing studies, the views from the clinical and patient community and what payers and/or healthcare commissioners
want to see before RDN could be used in routine clinical
practice.
What Clinical Evidence Is Missing toDate?
Long Term Safety withRDN Procedure
The Clinical Consensus Conference on device-based therapies
for HTN recommended post procedure safety surveillance for
at least 3years [6, 7]. In line with this recommendation, current studies have monitored the kidneys and renal arteries
closely at regular intervals using renal imaging (Doppler and
CTA/MRA scans) and biochemical assessment of renal function. To date there have been no short-term safety concerns in
any of the studies. Extended safety data available for 12months
from the RADIANCE- HTN solo study and up to 3years from
the Global Symplicity Registry study have not identied any
safety concerns in the longer term [8, 9]. A meta-analysis of 48
study cohorts found no statistical difference in estimated glomerular ltration rate (e-GFR) after an average follow up of
9months [10]. Hence, the short to medium term safety prole
with RDN remains good.
However, longer-term safety data with RDN extending up
to 5years will be more reassuring to patients and clinicians.
Most of the current safety data is from high volume device
centres using highly experienced interventionists, with every
procedure being proctored by the sponsor. These study
patients have been followed up in a highly regulated clinical
trial setting. However, once the therapy is licensed and used
more widely in community settings with less experienced
centres and light monitoring, the safety prole may change.
© 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_26
247
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M. Saxena and M. D. Lobo
Experimental data also indicates that although RDN reduces
BP and improves renal function, there are potential safety
concerns in the acute setting as it can markedly compromise
compensatory hemodynamic responses to haemorrhage [11].
Durability ofBP Reduction withRDN
The current generation RDN studies have used robust randomised, blinded, sham controlled study designs to assess
change in ambulatory BP as the primary efcacy endpoint at
2-, 3- or 6-months post procedure showing consistent reduction in ambulatory and ofce blood pressures [12].
Subsequently treatment changes were allowed, as it would
be unethical to allow patients to have sub-optimal BP control
for prolonged period. These medication changes make direct
assessment of durability of BP reduction with RDN challenging. However, data from the Radiance HTN Solo study
at 6months show signicant reduction in daytime ambulatory SBP in the RDN cohort compared to sham after making
adjustment for number of medications [2]. After 12months,
RDN patients were prescribed signicantly fewer medications compared to the sham group with no difference in
24-hour ambulatory BP [8]. The 3-year follow up data from
the international Global Symplicity Registry shows a 24-hour
systolic BP reduction of 8.9mmHg and 8.7mmHg in patients
with resistant hypertension [9].
The re-innervation of the denervated kidneys has been
postulated as a possible reason for loss of durability of BP
reduction [13]. Long-term data from post renal transplantation patients did not show any clinically meaningful reinnervation [14]. In summary, the BP reduction with RDN is
durable at 3-year follow up but it would be reassuring to have
longer term BP durability data. Previous CV outcome studies assessing novel pharmacological BP lowering therapies
such as ASCOT-BPLA had a median follow up of 5.5years
[15], even though the main objective was to assess effect on
outcomes.
In Dierent Patient Groups
To date, RDN has demonstrated BP lowering efcacy in different cohorts based upon grade of hypertension: in unmedicated patients with mild-moderate HTN and in those with
more severe resistant HTN despite antihypertensive medication [1–5]. Notably, all of these studies have targeted patients
with combined systolic-diastolic phase HTN and secondgeneration studies have excluded patients with the isolated
systolic HTN (ISH) prole.
The ISH phenotype with wide pulse pressure is mostly
attributed to ageing-related arterial stiffness [16]. Also, CV
risk increases with age and any BP-lowering intervention
will be benecial in lowering CV risk in this higher risk population. There is a need for robust, evidence-generating studies in ISH cohorts to demonstrate efcacy and safety of RDN
in patients with established arterial stiffness conrmed by
standard techniques such as aortic pulse wave velocity and
carotid distensibility [16].
Also, current studies have enrolled patients with preserved renal function (having eGFR > 45 mls/minute) and
have excluded chronic kidney disease (CKD) patients with
more severe renal dysfunction. Initial pilot data from a RDN
study in patients with eGFR <45 mls/minute has not raised
any safety concerns but long term data from larger cohorts of
patients with advanced CKD is required and is currently the
subject of ongoing studies [14], NCT04264403.
Besides HTN, many other diseases such as congestive
heart failure, chronic kidney disease, obstructive sleep apnea
and rhythm abnormalities are characterised by an overactive
sympathetic nervous system (SNS). Experts have argued that
RDN could be more successful in treating some of these
sympathetically-driven disease processes compared to HTN
[17]. Studies are planned in these patient cohorts in the future
(NCT02064764 and NCT02115100) but currently, there is
no existing data in these high-risk CV cohorts except for post
hoc analysis from existing studies [9].
Predictors ofResponse andPatient Selection
The recent Symplicity and Radiance RDN studies have
shown marked heterogeneity in BP responses following
RDN and about 25–30% of patients not responding at all or
even demonstrating increasing BP post-RDN [1–5]. Posthoc analysis of prior studies with RF RDN have identied
baseline systolic BP (SBP), younger age, higher eGFR,
higher HR, use of central sympatholytic agents or aldosterone antagonists, indices of baseline sympathetic overdrive,
and various biological markers as markers of response to
catheter-based RF RDN [18–22]. A post-hoc analysis of the
RADIANCE-HTN SOLO study identied use of antihypertensive medications at screening, higher baseline daytime
ambulatory diastolic BP (dADBP), abdominal obesity,
female sex, and orthostatic HTN (OHTN) as positive predictors of BP response to endovascular ultrasound RDN [23].
The positive predictors of BP response to US RDN were
mainly linked to heightened sympathetic nervous system
(SNS) activity in addition to anatomical predictors.
We need better anatomical, biological and clinical predictors of the BP response to RDN that will help in better patient
selection for RDN therapies. Ideally, predictors of response
should be non-invasive, cost-effective and easy to use in clinical practice. Several post-hoc analyses have identied certain patient phenotypes with SNS over activity (female sex,
abdominal obesity, OHTN, raised DBP) [23] that show big-
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249
ger BP reduction following RDN and meet these criteria but
their clinical utility needs to be demonstrated in prospective
studies in larger cohorts.
Markers ofProcedural Success
RDN remains a black box procedure with no validated markers identied to conrm procedural success in real time. The
role of sympathetic over activity in pathophysiology of HTN
is well recognised [24–26]. Animal and early human RDN
studies have demonstrated reduced sympathetic outow post
RDN with reduced renal norepinephrine spillover [14] and
reduced muscle sympathetic nerve activity (MSNA) post
RDN [27, 28]. But these assessments are difcult to undertake and limited to very few specialised centres.
Data from the Spyral HTN-OFF MED study in drug naïve
patients showed reduced plasma renin activity with RDN
and has been identied as a predictor of response [29] but
this has not been shown in other studies [30]. Attenuation of
(sympathetically driven) splanchnic autotransfusion during
the Valsalva manoeuvre has also been identied as a marker
of procedural success [31] but needs to be conrmed in bigger studies.
The clinical community and regulatory bodies would like
to see real-time validated markers of procedural success that
could both help to understand the heterogeneity in BP
response with RDN and also help to eventually further rene
the procedure towards improved outcomes.
Eect onCV Outcomes
Current RDN studies were powered to show efcacy in lowering BP but not for CV outcomes. Accordingly, the lack of
CV outcome data with RDN therapies has been quoted as
one of the biggest gaps in the evidence gap and a potential
barrier to routine clinical adoption [32]. In current health
environment, most novel therapies targeting CV risk factors
(for example dyslipidaemia, heart failure, diabetes) are
approved and included in treatment guidelines based on outcome data.
However, it can be challenging to quantify the effect of
certain novel interventions such as RDN on CV outcomes as
this would requires evaluation in a large cohort of high-risk
patients followed up for a prolonged period to capture the
effect of the intervention on outcomes. The eligible cohort
for RDN therapies is difcult to nd and is comparatively
smaller based on anatomical suitability. With a risk factor
like HTN, it would be unethical to leave patients in a control
or sham arm with sub-optimal BP control for too long. Some
of the other constraints of running a big CV outcome study
include the high cost of running such a trial, the difculty of
maintaining blinding over the longer term, challenges to
maintain medication adherence given variable patient adherence and the failure of clinicians to adhere to medication
titration protocols in rigorous trials to date and unlikelihood
of recruiting patients to such a study given alternative RDN
technologies on the horizon with shorter term studies.
Considering these challenges, currently there are no
ongoing or forthcoming RDN studies looking at effect on
CV outcomes and we need to infer the effect of BP lowering
with RDN on CV outcomes. Meta-regression analysis of the
3 year data from the Global Symplicity Registry shows a
relative risk reduction for major cardiovascular events by
26% and for stroke by 34% assuming that baseline Systolic
BP would be maintained [12]. Of note, RDN has a 24-hour
BP lowering effect and lowers BP during both day and nighttime on 24-hour ambulatory BP monitoring. It is well known
that nighttime lowering of BP is a better predictor of CV
outcomes than daytime BP reduction [33, 34]. Also, RDN
has shown to attenuate the morning surge in BP that is known
to have adverse prognostic signicance [35].
HTN is an established surrogate for CV diseases. The
association between elevated BP with CV outcomes [33] and
the benecial effect of lowering of high BP on CV events and
death is well recognised [36]. In three meta-analyses, reduction in systolic BP with pharmacotherapy was associated with
reduced incidence of major CV events and according to metaregression analyses, even in a linear relationship [12, 36–38].
This benecial effect of BP lowering with pharmacological
treatment on CV outcomes is largely related to BP lowering
regardless of how this BP reduction was achieved.
Hence, it is fair to conclude that it may not be feasible to
run CV outcome studies with RDN but it is very likely that
BP lowering with RDN will lead to improvement in CV outcomes. Once the therapy is licensed and used more widely,
real world registry studies could be used to gather direct data
on CV outcomes.
What Is theView oftheUsers: Clinical
Community andPatients?
Clinical Community
The clinical community has mixed views about the use of
RDN for treatment of uncomplicated HTN. It has been
argued that rather than targeting uncomplicated HTN, one
should aim to use RDN to treat high risk hypertensive
patients with other CV co-morbidities [12]. It can be used in
primary prevention of Atrial Fibrillation in a hypertensive
patient population enriched by an increased CHA2DS2-VASc
score [39]. Some clinicians have suggested CV outcome
studies in high-risk patients with sympathetically driven CV
co-morbidities such as heart failure, diabetes mellitus, sleep
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M. Saxena and M. D. Lobo
apnoea, and arrhythmias [40]. RDN might also be deployed
for cardiac remodelling in patients with acute myocardial
infarction and/or heart failure that is primary driven by
increased SNS activity [41].
Consensus Statement fromAcademic Bodies
The ESH 2021 consensus statement on RDN [12] acknowledges “RDN as an evidence-based option and safe endovascular procedure to treat HTN in addition to lifestyle and
anti-hypertensive medication. RDN is an alternative or additive, not a competitive treatment strategy. It recommends a
structured pathway for clinical use of RDN in daily practice
taking patients perspective and preferences on individualized
treatment strategy into consideration”. It also identies
major gaps in knowledge that we have discussed above.
The 2020 Consensus Statement of the Asia Renal
Denervation Consortium acknowledges “RDN as an effective HTN management strategy in Asia that should not be
considered a therapy of last resort but as an initial therapy
option that may be applied alone or as a complementary
therapy to antihypertensive medication with patient preference for device-based therapy taken into consideration as
part of a shared patient-physician decision process” [32]. It
also recommends “new randomized clinical trials of RDN
in Asia focusing on uncontrolled morning hypertension
and, ultimately, clinical outcomes to further optimize treatment” [32].
The US Society of Cardiovascular Angiographies and
Interventions (SCAI) 2021 consensus statement on RDN
highlights RDN potential to improve public health outcomes
and address an epidemic of uncontrolled hypertension with
future steps to identify appropriate patients and build an
interdisciplinary network for referrals.
Patient preference Data
Regulatory bodies now take into account the patient’s perspective and preferences for novel therapies and require that
these are assessed as a pre-requisite for market authorisation.
Previous survey studies have captured hypertensive patients’
perspective about their disease and preference towards RDN
therapy [42]. A cross sectional epidemiological survey study
[43] showed roughly one third of hypertensive patients
would have preferred RDN compared to lifelong pharmacotherapy to lower their BP.However, larger studies in patients
with different grades of HTN are needed in this eld to capture patients’ preference towards RDN across a broader
spectrum of indications.
What Do Payers/Healthcare Commissioners
Want toSee?
What Does it Take toGet RDN Commissioned?
The path towards adoption of RDN as a standard of care
therapy for hypertension requires both approval by regulatory authorities and formalised reimbursement codes. There
is need for clarity about acceptable cost effectiveness for
device-based therapies such as RDN. The reimbursement
model will vary in different health economies based on
health care funders (state or private health insurance) and
priorities, and it will dene country-specic patient pathways for accessing RDN therapies. Despite all the efcacy
and safety data from these RCTs, it presently remains unclear
as to what evidence is needed to get RDN commissioned and
funded as a routine clinical service.
Which Energy Modality?
Current Guidelines
The last ESC/ESH guidelines issued in 2018 [33] for management of arterial HTN came out before the second generation pivotal sham-controlled RDN studies were published. In
the absence of this data, they did not recommend the use of
device-based therapies for the routine treatment of hypertension, unless in the context of clinical studies and RCTs, until
further evidence regarding their safety and efcacy becomes
available. Now that there is more robust evidence available
from a few RCTs, guidelines review should happen earlier to
evaluate new data on RDN.In the UK, the National Institute
of Health and Clinical Excellence (NICE) is currently undertaking a technology reappraisal of guidelines IPG418 (initially published in 2012, last updated in 2016) and plans to
publish this in summer 2022.
Based on current data, RF and US technologies are closer to
market authorisation, whereas pivotal studies with alcohol/
chemical RDN are still ongoing. There have been few direct
head-to-head comparison studies between different technologies and catheter systems so far. There is only one openlabel, single-centre study [44] that compared RF RDN of the
main renal artery with RF RDN of main artery and branches
and US RDN (main artery & large branches). The RF RDN
of only the main artery was inferior to the other two but there
was no signicant difference in BP reduction between US
RDN and RF RDN of main artery and the branches [44].
Once RDN is clinically commissioned, patients and clinicians would like to see more efcacy/ safety data from comparator studies to decide which energy modality or catheter
system is better suited for individual patients based on renal
vasculature. If there are signicant differences in hardware/
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251
procedural costs, there could be substantial variation in costeffectiveness with individual technologies that could prioritise one approach over the other.
Who Is Likely toGet RDN?
RDN being an invasive therapy and comparatively expensive,
regulators and commissioners would like to see demonstrable
benet with CV risk reduction. Hence, it might be easier to
justify initial use of the therapy in difcult to control (resistant
HTN) or high-risk CV patients with multi- morbidities such as
previous CV events, CKD, diabetes mellitus, atrial brillation,
congestive heart failure and obstructive sleep apnoea compared to making RDN available in younger, healthier patients
who do not want to take anti- hypertensive medication as a lifestyle choice. There are considerable cost implications to the
latter given the global burden of hypertension and patient preference to avoid lifelong drug therapy. Another high risk, difcult to control cohort of patients who could be considered for
priority access to RDN could be patients with multiple drug
intolerances to anti-hypertensive drugs [45]. These patients
with multiple medication intolerances and poor quality of life
have very few treatment options and would benet more from
BP reduction and consequent CV risk reduction than a lowrisk population.
Geographical Considerations
Commissioning and patient pathways for RDN will depend
upon regional or National guidance. In Germany, a consensus
statement of the German Cardiac, Nephrology and Hypertension
Society has been published describing how RDN should be
implemented into clinical practice, focusing on hospital facilities
capability and capacity for elective RDN procedures [12].
Currently, RDN is commissioned on a limited basis for routine
clinical use in Germany and Switzerland in Europe.
In the UK, the route to routine commissioning involves
the ongoing review by NICE and thereafter is likely to pass
directly to NHS England Specialised Commissioning for
development of a commissioning policy. The benet of a formal Health Technology assessment review by NICE would
be the capacity to incorporate a clear focus on quality
adjusted life years (QALYs) as a measure of patient and
health system value.
In the United States, RDN technologies could be reviewed
for market authorisation by the FDA as early as next year
once the pivotal studies with US and RF technologies are
completed.
Conclusion
The latest consensus statements by academic bodies from
Europe, the United States and Asia are increasingly supportive
of RDN as a potential treatment for HTN.Once approved by
the regulatory bodies, it needs to be seen how it is commissioned and reimbursed in different health care settings. The
initial cohort of patients having access to RDN is likely to
include high risk resistant HTN patients with CV co- morbidities
and may extend to patients with multiple intolerances to antihypertensive medication with very few treatment options. At
this stage, it will be difcult to justify offering RDN to mild to
moderate uncomplicated hypertensive patients who not do not
want to take BP lowering medication as a lifestyle choice.
At a national and regional level, there should be well
dened patient identication and referral pathways around a
few dedicated and experienced, selected referral centres as
Germany is planning [12]. It is important to take into account
capacity and capability of these centres to perform elective
RDN and the scope to provide multi-disciplinary inputs. But
at the heart of all this structure, there should be valid tools to
capture patient’s perception about their current disease management and their preference for device therapies as a treatment option for their HTN leading ultimately to shared
decision making with their physicians based on the latest
risk/ benet evidence.
As clinicians and key opinion leaders have argued, we
need to explore RDN in additional indications and high-risk
patients characterised by SNS overactivity such as HTN with
AF, CHF, CKD and OSA.These are the cohorts who might
get maximum benet from sympatho-modulation achieved
by RDN. This cannot be achieved by industry alone and
needs nancial support from charities, funding bodies and
governments. This can be done by setting up real world
National registries using global harmonised protocols, targeting well dened patient population stratied by risk and
collating data globally to have adequately powered dataset to
test different hypotheses. In the fullness of time, evidence
from such real world studies in larger populations will help
to better identify predictors of response and possibly dene
procedural markers of success that in turn would help
improve patient selection and reduce numbers of nonresponders to the therapy.
Declaration of Interest Dr. Saxena has received institutional grant from Recor Medical Inc., Ablative Solutions
Inc., Vascular Dynamics Inc., Applied Therapeutics Inc. He
reports consultancy with Recor Medical Inc., Daiichi Sankyo
Inc., Esperion Therapeutics, Vifor Pharma, Novartis,
Boehringer Ingleheim.
252
https://t.me/medicina_free
M. Saxena and M. D. Lobo
Prof Lobo is a consultant to Medtronic, ReCor Medical,
Ablative Solutions, Aktiia and Vascular Dynamics. He has
received educational grants from Medtronic and ReCor
Medical and speaker fees from CVRx.
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