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256
Table 14.2 (continued)
Original studies
Author
Procedure Follow-up time
Dardik [45] CEA 3months 0% 8%
2001
Key
ndings:
Middleton [46] CEA NR 1.7% NR
2001
Key
ndings:
Lloyd [47] CEA 6months 0% NR
2004
Key
ndings:
CaRESS [48] CAS 30days, 1year 0.0% CAS vs.
2005 CEA
Key
ndings:
Abelha [49] CEA 6months 0% 4.8%
2008
Key
ndings:
Stolker [50] CAS 2weeks, 1month, 6months, 12months NR NR
2010 CEA
SAPPHIRE
Key
ndings:
Attigah [51] CEA Baseline, 2days 0% 0%
2011
Key
ndings:
Perceived improved overall health after CEA
SF-36 scores in all domains similar at 3months compared to baseline
Postoperative physical health similar to chronically ill general population
Postoperative mental health similar to healthy general population
At 1year, majority of patients consider overall health to be similar to pre-op
SF-36 scores higher in CEA cohort than population norms for Australian
>55years old who had experienced a stroke, but not compared to general healthy
population
CEA did not cause deterioration of QOL at 6months
Signicantly less anxiety after the operation based on HAD scale
Signicant improvement in QOL according to EQ-5D scale
No signicant differences between CEA and CAS groups in change of QOL and
MILQ score
CAS experienced greater decline in QOL after intervention, but it was not
statistically signicant
Improved subjective perception of QOL
Higher levels of dependency in activities of daily living
Worse SF-36 scores compared to general population
Physical health domains decline at 2weeks after CEA, and return to baseline by
1month
At 2weeks, CAS patients had better scores in SF-36 physical scale compared to
CEA
No signicant difference in SF-36 scores at 1month, 6months, 12months
Mental health scores similar at all time intervals
EQ-5D utility score similar
At 2weeks CAS patients reported less difculty eating, swallowing, difculty
driving and less neck pain. These differences resolved by the 1month follow-up
assessment
Procedural satisfaction better in those who already have worse HADS scores
Perioperative
mortality
0.4% CEA
L. L. Shan et al.
Perioperative
strokeYear
2.1% CAS vs.
3.6% CEA

14 Quality ofLife andPatient Reported Outcome Measures Following Carotid Artery Intervention
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Table 14.2 (continued)
Original studies
Author
Procedure Follow-up time
Cohen [52] CAS 2weeks, 1month, 1year CAS 5.2% vs.
2011 CEA
CREST
Key
ndings:
Kazmierski
[33]
2012
Hsu [53] CAS Baseline, 1month, 6months 0% 0%
2014
Kazmierski
[54]
2014
Yan [55] CAS Baseline, 1month, 3months, 6months,
2014
Carta [56] CEA 6–7months NR NR
2015
Hye [57] CEA Baseline, 2weeks, 1month, 12months NR NR
2015
CEA 1year NR NR
Key
ndings:
Key
ndings:
CEA Baseline, 1year NR NR
Key
ndings:
Key
ndings:
Key
ndings:
Key
ndings:
After CEA, physical and functional health domains of SF-36 worse at 2weeks, but
return to baseline or better by 12months
After CEA, mental health domains of SF-36 continuously improve, including at
2weeks
Better SF-36 scores for CAS at 2weeks compared to CEA (SF-36, disease specic
scales, pain scale), but not after 1month, and are the same at 1year
LS scores for pain and function similar for both CEA and CAS at 1year
Postoperative stroke has negative impact on QOL, but not myocardial infarct or
cranial nerve injury
Mean QOL after surgery increased 1year after surgery
Before surgery: “poor” (more than half). After surgery “good” (86%).
All SF-36 domains similar to baseline at 1month after CAS
At 6months, physical and general health domains better, less pain, emotional and
social function better
Asymptomatic patients maintain preoperative QOL
Majority of patients have signicant functional improvement after CEA
Patient’s life quality improved in 67% patients
12months
WHOQOL-BREF improved at 1month, 3months, 6months, 12months after
CAS compared to baseline
HAM-D and HAM-A were better after CAS compared to medical therapy at all
postoperative time points
SF-12 score similar between CEA and medical treatment groups
Positive trend towards better QOL outcomes after CEA, but 6months not enough
to demonstrate this
No signicant difference between preoperative and postoperative scores
No difference in QOL between patients with and without cranial injury after CEA
LS showed cranial nerve injury had some negative impact on functional status
Perioperative
mortality
CEA 4.5%
0% 0%
257
Perioperative
strokeYear
4.1% CAS vs.
2.3% CEA
(continued)

258
Table 14.2 (continued)
Original studies
Author
Procedure Follow-up time
Reviews
Al-Damluji
[42]
2013
Shan [28] Key
2015 Minimal differences between CEA and CAS
Chabowski [43] Key
2017 1year QOL similar to chronically ill general population
ADL activities of daily living, BP bodily pain, CaRESS carotid revascularization using endarterectomy or stenting systems trial, CAS carotid artery stenting, CEA carotid endarterectomy, CREST carotid revascularization endarterectomy
versus stenting trial, EQ-5D European quality of life questionnaire EQ-5D, GHP general health perception, QOL quality of life, ICU intensive care unit, MH mental health, MILQ multidimensional index of life quality, NA not applicable,
NR not recorded, NS not signicant, PF physical function, Post-op post-operative, Pre-op pre-operative, RE role emotional/mental, RP role physical, SAPPHIRE stenting and angioplasty with protection in patients at high risk for endarterectomy, SF social functioning, SF-36 medical outcomes survey short form 36 questions, VAS visual analogue scale,
VT energy/vitality
Key
ndings:
ndings:
ndings:
CAS patients have better QOL at 2weeks postop compared to CEA patients, but
no difference by 1year
CEA and CAS maintain preoperative QOL for at least 1year
Early postoperative QOL after CEA declines, but returns to baseline at 1year
Perioperative
mortality
L. L. Shan et al.
Perioperative
strokeYear
Quality ofLife After Carotid
Endarterectomy (18 Studies)
[28, 31–33, 42–52, 54, 56, 57]
The vast majority of QOL evidence pertains to
CEA.Numerous studies demonstrate that patients
maintain pre-operative QOL after CEA.The pattern of recovery varies across different domains
in different studies. There is a temporary decline
in QOL at 2weeks to 1month especially in physical health and functional domains. This is only
transient and is consistent with the expected initial postoperative decline after open surgery.
However, by 6months to 1year, all domains are
at least as good as pre-operatively.
The preservation of mental health is important
after carotid intervention, particularly in prophylactic procedures. Patients with carotid stenosis
already have a baseline level of anxiety and poor
perception of health related to overall poor cardiovascular health [47]. Studies included in this
chapter show that unlike the physical health
domains, mental health domains did not demonstrate the same pattern of initial decline after surgery. Instead, QOL appears to be maintained
throughout.
A major limitation of these studies should be
highlighted here. There remains only one study
with QOL data beyond 12 months [31]. This
study is one of the earliest studies on QOL after
CEA and is therefore limited because modern
operative techniques and validated QOL instruments haven’t been used. While it is difcult to
draw strong conclusions, these authors demonstrated that after 8–11 years’ follow-up, QOL
remained similar between the CEA and nonoperative groups with relatively similar response
rates. This suggests a positive long-term QOL
outcome after CEA.
Quality ofLife After Carotid Stenting
(Seven Studies) [28, 42, 48, 50, 52,
53, 55]
Overall, QOL does not appear to deteriorate after
CAS. Earlier studies show that although some
health domains were temporarily worse, QOL at
1year is similar to baseline. Contemporary studies suggest that CAS patients have similar QOL
by 1 month and may actually experience an
improvement in their physical and general health

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259
domains with better emotional and social function by 6months. To date there is no data on QOL
after CAS beyond 1year.
Quality ofLife After Endarterectomy
Compared toStenting (Five Studies)
[28, 42, 48, 50, 52]
CAS may be superior to CEA in the early postprocedure period in physical health domains
from as early as 2weeks. However, these differences were not present at 1year. A similar pattern
is observed in functional performance with no
difference in walking, eating and driving ability
by 1year. Mental health domains do not appear
to be impacted by the type of procedure. Based
on these results where QOL is similar, the choice
between CEA and CAS is likely to be inuenced
by other factors.
Quality ofLife Compared
toReference Populations (Seven
Studies) [31, 32, 45, 46, 49, 55, 56]
Comparisons have been made between carotid
intervention and medical treatment groups or the
general population. It is clear that current data
remains insufcient to be denitive. After CEA,
there does not appear to a clear difference in
QOL between intervention and medical treatment groups at follow-up of up to 1year, especially in physical health domains. Treatment
satisfaction remains high, but anxiety over future
strokes or TIA may remain. These anxieties
appear to be lesser after CAS at short follow-up.
CEA patients have worse physical health compared to the general population, but mental health
may be similar. The lack of benet compared
with medical treatment groups and the general
population is largely due to the short term follow up. Stroke prevention in carotid intervention is
greater the longer the follow-up. Therefore, it is
likely that there has not been enough time elapsed
to identify a QOL benet of intervention.
Cognitive Function
There has been a greater interest recently in cognitive outcomes after carotid intervention. A
number of reviews and meta-analyses have been
published on this subject, but denitive conclusions have not been reached due to signicant
heterogeneity. CEA may be associated with both
preservation and improvement of cognitive
function depending on the domain tested [58–
61]. This includes memory, attention, mini men-
tal state exams, and executive function. CAS may
be associated with improved global cognition,
memory, attention and psychomotor speed,
although executive function and language may
not change [62]. The difference between CEA
and CAS remains unclear [61].
Utility ofQuality ofLife Tools
Importance ofQuality ofLife
Assessment andPROMS
A recent review by the Australian Commission
on Safety and Quality in Health Care has identied some key aspects of PROMS and QOL [25].
QOL and PROMS are used because patients are
the best judges of the effect on their QOL and
function. This allows a patient centered model of
care and helps improve the quality and safety of
various treatments. The effectiveness of different
treatments can therefore be more accurately
determined.
With carotid revascularisation, the inference
previously has been that intervention prevents
QOL deterioration due to stroke prevention. It is
only recently that QOL outcomes have been formally reviewed [28, 42, 43], showing the positive
outcome of carotid revascularisation on QOL and
PROMS. There should be distinction between
asymptomatic and symptomatic patients in order
to use QOL in clinical practice.
QOL should not necessarily be expected to
improve after revascularisation, particularly for
previously asymptomatic patients who have pro-

260
L. L. Shan et al.
phylactic procedures. The outcome is positive if
QOL is maintained after intervention because the
intervention served to prevent a stroke. This is
especially important in prophylactic procedures,
especially if performed on asymptomatic patients
who would otherwise not have had a detriment to
their QOL as a result of the disease process.
Similarly, because they were asymptomatic, they
were unlikely to gain a great benet from intervention other than in mental health domains.
In symptomatic patients who have had a
stroke, there may be a signicant deterioration in
QOL before intervention. Subsequent revascularisation and resolution of symptoms in conjunction with rehabilitation may then improve
QOL. The recovery in QOL will then likely be
longer than in asymptomatic patients. There will
also likely be positive effects on mobility indices,
Rankin score, and mini mental state, but these are
yet to be elucidated in studies. Existing QOL
studies do not make a distinction between transient ischemic attacks and stroke as the indication
for carotid revascularisation. By denition,
patients with transient ischemic attacks don’t
have residual physical neurological decits and
therefore physical domains of QOL are much less
impacted than a patient with stroke. Mobility and
disability are also likely to be different. Fear of
subsequent stroke is more likely to be a key feature in transient ischemic attacks, and this affects
mental health domains much more.
With implementation of these guidelines,
important and clinically relevant information
would be obtained. This information provides
improved patient-focused outcomes data which
facilitates improved quality of care to patients and
more accurate analysis of the effectiveness of an
intervention. In addition, perhaps the greatest benet will be its use in policy making, costeffectiveness analysis, and ultimately resource
allocation. For example, CEA has been shown to
be cost effective even in asymptomatic patients less
than 75years of age if a threshold of £20,000 per
quality of life year and background stroke rate of
less than 1% per year is used [63]. The cost effectiveness of CAS compared to CEA is not so clear
[64–66]. QOL and cognitive function have not yet
been included in such cost- effectiveness analyses.
Need forFurther Research
There are several key issues identied from previous QOL studies that should be addressed in
future studies [28].
Firstly, and perhaps most importantly, there
needs to be investigation into the long-term QOL
outcomes after carotid intervention. The benet
of stroke prevention is likely to be greater the
longer the follow-up. This is especially important
in asymptomatic carotid intervention. Current
QOL outcomes are largely limited to 1year, but
these outcomes would be more even more relevant if follow-up extended up to 5years.
Secondly, there is a clear lack of evidence on
the use of currently available QOL and PROM
instruments after carotid revascularisation [67].
These disease-specic QOL instruments are useful measures of change in QOL specic to a treatment and disease process [27]. However, there
are signicant difculties with developing such
QOL instruments because there would need to be
separation of symptomatic and asymptomatic
patients, transient ischemic attack and stroke
patients, as well as degree of stenosis. It may be
better to apply the currently available neurological QOL instruments and mobility and disability
indices in carotid intervention.
Thirdly, there needs to be a standardised set of
results that are reported to facilitate objective
assessment with meta-analyses. Ideally a standardised common instrument should be used by
all studies. QOL data should be expressed as
mean ±standard deviation and results given at
pre-determined follow-up time points including
baseline and nal follow-up, rather than a range
or median of variable follow-up time points.
Fourthly, there was a relatively low response
rate in previously conducted studies. High
response rates are compulsory to minimise bias.
Fifthly, the distinction between symptomatic
and asymptomatic patients for both CEA and
CAS is unclear. These are markedly different
subgroups of patients in regard to baseline QOL,
expected QOL gains, and importantly the
patient’s own expectations after intervention.
Finally, the effect of morbidity, frailty and disability as a variable for QOL outcomes is under-

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appreciated. The burden of comorbidities is a risk
factor for frailty, which in turn predisposes to disability [68]. This is because frailty causes
decreased reserve and less ability to deal with
adverse outcomes [68]. Comorbidities, frailty
and disability are therefore separate entities.
They are important because they are increasingly
prevalent with an ageing population, who are
Older
age
Severe
stroke
increasingly offered intervention. There are also
specic stent technologies, stent brands, and
Comorbidities
adjuncts to improve procedural success of CAS
in specic anatomical set ups. However, the
impact of these on QOL outcomes have not been
Socioeconomics
investigated.
With implementation of these guidelines,
important and clinically relevant information
would be obtained. The logistical challenges
Inadequate
treatment
faced will be in the design of an instrument which
is simple and thorough enough for patients to
participate in, as well as the data collection which
Fig. 14.1 Predictors of poor QOL
needs to be consistent and accurate without signicant loss to follow-up. The importance of this
aspect of treatment is often underestimated as the
traditional teaching heavily emphasises the
importance of technical outcomes alone. This
paradigm now needs to incorporate QOL outcomes as a complement to technical outcomes as
a routine part of clinical practice.
this text. In order assess the relevance of QOL
outcomes, it is more important to assess the
reported morbidity and mortality in the studies
that report QOL.Any patients who do not participate in QOL assessment or are lost to follow-up
are more likely to have a worse QOL due to a
greater burden of comorbidities and physical
impairments [49, 50]. The difculty in
interpreting QOL assessments is compounded by
Eect ofOther Outcomes onQuality
ofLife andProms
the fact that post-operative stroke and death renders it unlikely that such patients will complete
QOL questionnaires. According to previous
Predictors of QOL outcomes have been studied
after CEA (Fig. 14.1) [43, 69]. Worse QOL is
likely after severe stroke, older age, comorbidities, lack of proper treatment and rehabilitation,
and poor socioeconomic factors [43]. Mental
health domains of QOL after signicantly
affected by contralateral stenosis, dizziness
improvement, and hoarseness [69]. This shows
that although uncommon, vagus nerve injury
should be avoided during CEA by meticulous
dissection and avoidance of retractor injury.
The mortality, survival, morbidity and complications of CEA and CAS are well described in
the literature. These are outside of the scope of
guidelines, a response rate of >85% (loss to follow-up <15%) is considered ideal [70]. This rate
is achieved in only eight studies in the literature
[33, 45–47, 51, 52, 56, 57]. It is therefore possible that QOL outcomes are overestimated, at
least in the shorter term. At the same time, the
lack of adequate long- term follow-up may also
underestimate the QOL benet because the benet of CEA for stroke prevention is more apparent the longer the follow-up duration. It is
therefore important to assess the both the shorter
and longer-term response rates to identify risk of
bias in conjunction with the technical outcomes
to put the QOL outcomes into perspective.
261

262
L. L. Shan et al.
Statistical techniques to deal with missing data
have been developed to resolve issues such as
mentioned above. This includes multiple imputation which is a statistical method of dealing with
missing data by combining the results of several
different possible data sets [71]. There are particular biases that occur as a result of the missing data,
depending on the reason why the data is missing.
Multiple imputation may be helpful in both epidemiological studies and randomised controlled trials, but there are potential pitfalls that warrant
input from a statistician [71, 72]. Future studies
may benet from incorporation of this technique.
Perioperative mortality and stroke was analysed in studies reporting QOL data. The perioperative mortality and stroke rate are CEA was
0.0–4.5% and 0–8.0%, respectively [32, 44–49,
51, 52], while after CAS it was 0.0–5.2% and
0–5.8%, respectively [48, 52, 53, 55]. Perioperative myocardial infarction was 0.8–6.6% in
CEA and 0.0–1.9% in CAS [16, 23, 48, 50, 52].
The 1-year stroke rates for CEA and CAS were
7.7–9.8% and 5.5–5.8%, respectively [23, 48,
50]. These results are reective of the studies
included which were not designed to evaluate
stroke and mortality rates, with few randomised
controlled trials and high quality studies in this
regard. While the results don’t necessarily reect
that of currently accepted standards, they do provide an indication of how the QOL results from
these studies can be interpreted. The mortality
and stroke rates are in general higher, meaning
QOL outcomes may be worse than if QOL data
were derived from higher quality studies.
Few studies reported comprehensive morbidity data. Patients in included studies experienced
fewer stroke symptoms after CEA compared to
CAS [33]. Symptoms including headache, leg
pain were similar in CEA and CAS after 1year
[52], although there may be more neck pain with
CEA [50]. Cranial nerve palsies occurred in 0.3%
and 4.7% of CAS and CEA patients respectively
[52]. However, cranial nerve injury does not
appear to cause a detriment to overall QOL [57].
The effect of perioperative morbidity and complications on QOL outcomes and PROMS
remains unclear. Given the relatively low inci-
dence of complications in experienced centres, it
may not be possible to demonstrate a statistically
signicant impact. However, clinically it would
be prudent to avoid complications and improve
morbidity to avoid a negative impact on QOL.
Cognitive function is a relatively new area of
interest in carotid intervention. The reason for
cognitive impairment from carotid disease and
intervention may relate to brain injury which
occurs due to embolism, thrombosis or hyperperfusion/hypoperfusion [73]. Atheroembolism in
particular is associated with worse short and long
term cognitive function [74, 75]. There is also a
theory that the greater embolization rate during
CAS may account for a worse cognitive outcome,
but this is not yet conrmed [61]. Cognitive outcomes following carotid revascularisation are
important because these affect how a patient perceives their QOL and also how they report their
QOL.Furthermore, if a patient has severe cognitive impairment, it may signicantly limit their
ability to accurately report on their own
QOL. Further research is necessary to identify
the impacts of cognitive function on PROMS in
these patients.
Conclusion
Currently available studies show that CEA and
CAS maintain pre-operative QOL for at least
1year (Fig. 14.2). Long-term data is lacking and
there is insufcient evidence to differentiate CEA
and CAS.QOL and PROMS are a critical aspect
of outcomes assessment in modern surgical practice. This is particularly pertinent to preventative
procedures such as CEA and CAS. Signicant
limitations of the currently available literature are
identied with the view that these be used as a
guideline for future research. This information
provides improved patient-focused outcomes
data which facilitates improved quality of care to
patients and more accurate analysis of the effectiveness of an intervention. In addition, perhaps
the greatest benet will be its use in policy making, cost-effectiveness analysis, and ultimately
resource allocation.

14 Quality ofLife andPatient Reported Outcome Measures Following Carotid Artery Intervention
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Conclusions
1. QOL and PROMS are critical in contemporary outcomes assessment after carotid artery
intervention.
2. CEA and CAS maintain pre-operative QOL for at least one year.
3. Long-term data is lacking and there is insufficient evidence to differentiate CEA and CAS.
4. Severe stroke, older age, comorbidities, lack of proper treatment and rehabilitation, and
poor socioeconomic factors are predictors of poor QOL after CEA.
5. Future studies are needed to improve methods of QOL assessment and evaluate factors
that affect QOL outcomes especially after CAS.
Fig. 14.2 Conclusions
263
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