Age and Ageing 2022; 51: 1–8 © The Author(s) 2022.

hor(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics
https://doi.org/10.1093/ageing/afac096 Society. All rights reserved. For permissions, please email: [email protected]

RESEARCH PAPER

Effect of frailty on outcomes of endovascular

treatment for acute ischaemic stroke in older
patients

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

Benjamin Y. Q. Tan1,2,† , Jamie S. Y. Ho3,† , Aloysius S. Leow1 , Magdalene L. J. Chia1 ,
Ching Hui Sia2,4 , Ying Ying Koh2 , Santhosh K. Seetharaman5 , Cunli Yang2,6 ,
Anil Gopinathan2,6 , Hock Luen Teoh1 , Vijay K. Sharma1,2 , Raymond C. S. Seet1,2 ,
Bernard P. L. Chan1 , Leonard L. L. Yeo1,2,‡ , Li Feng Tan7,‡
1
Division of Neurology, Department of Medicine, National University Health System, Singapore, Singapore
2
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
3
Academic Foundation Programme, Royal Free London NHS Foundation Trust, London, UK
4
Department of Cardiology, National University Heart Centre, Singapore, Singapore
5
Division of Geriatric Medicine, National University Health System, Singapore
6
Department of Diagnostic Imaging, National University Health System, Singapore, Singapore
7
Healthy Ageing Programme, Department of Geriatric Medicine, Alexandra Hospital, Singapore, Singapore

Address correspondence to: Benjamin Y. Q. Tan, National University Health System, NUHS Tower Block Level 10, 1E Kent Ridge
Rd, Singapore 119228. Email: [email protected]
† These authors are co-first authors.
‡ These authors are co-senior authors.

Abstract
Background: frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases. Few
studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular thrombectomy
(EVT).
Objective: we aimed to investigate the impact of frailty measured by clinical frailty scale (CFS) on clinical outcomes after
EVT for acute ischemic stroke (AIS) in older patients ≥70 years.
Methods: in this retrospective cohort study, we included all consecutive AIS patients age ≥ 70 years receiving EVT at a
single comprehensive stroke centre. Patients with CFS of 1–3 were defined as not frail, and CFS > 3 was defined as frail. The
primary outcome was modified Rankin Score (mRS) at 90 days. The secondary outcomes included duration of hospitalisation,
in-hospital mortality, carer requirement, successful reperfusion, symptomatic intracranial haemorrhage and haemorrhagic
transformation.
Results: a total of 198 patients were included. The mean age was 78.1 years and 52.0% were female. Frail patients were
older, more likely to be female, had more co-morbidities. CFS was significantly associated with poor functional outcome after
adjustment for age, NIHSS and time to intervention (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.04–
2.28, P = 0.032). There was trend towards higher mortality rate in frail patients (frail: 18.3%; non-frail: 9.6%; P = 0.080).
There were no significant differences in other secondary outcomes except increased carer requirement post discharge in frail
patients (frail: 91.6%; non-frail: 72.8%; P = 0.002).
Conclusions: frailty was associated with poorer functional outcome at 90 days post-EVT in patients ≥ 70 years.

Keywords: frailty, ischaemic stroke, endovascular treatment, thrombectomy, older people

1
B. Y. Q. Tan et al.

Key Points
• Frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases.
• Few studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular
thrombectomy (EVT).
• Frailty was associated with poorer functional outcome post-EVT in older patients, independently of age, National Institute
of Health Stroke Scale (NIHSS) and time to intervention.
• Elucidating how frailty predicts clinical and functional outcomes in stroke can lead to better prognostication and decision-
making.

Introduction investigate the impact of CFS on clinical outcomes after EVT

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

for AIS in older patients ≥ 70 years.
Acute ischaemic stroke (AIS) is the second leading cause of
mortality globally, where 1 in 4 adults over the age of 25
will experience a stroke in their lifetime [1]. Frailty is a state Methods
of increased vulnerability to poor resolution of homeostasis
following a stress, and is associated with adverse outcomes Study population
such as increased mortality and hospitalisations [2]. In the In this retrospective cohort study, we included all consecu-
last 20 years, the incidence of stroke had increased by 70% tive AIS patients age ≥ 70 years receiving EVT at a single
and death from stroke increased by 43% [1, 3]. A meta- tertiary centre from 2017 to 2020. Data were extracted
analysis of 48,009 patients found that ∼22% of patients from a centralised, prospectively collected database, which
with AIS have frailty, and 49% had prefrailty or frailty [4]. included all cases of AIS patients presenting to the tertiary
As the age of the population increases, it is expected that hospital. The inclusion criteria are: (i) adults who had neu-
the absolute number and proportion of AIS patients with roimaging confirmed AIS, (ii) with anterior and/or poste-
frailty would increase, therefore it is of great importance to rior circulation AIS large or medium vessel occlusion and
understand the outcomes of acute stroke treatment in this (iii) underwent EVT within 6 h of symptom onset. Only
susceptible population. patients with a premorbid modified Rankin Scale (mRS)
Endovascular thrombectomy (EVT) is the standard of score of 0–2 qualified for EVT. We classified the site of
care for AIS due to large vessel occlusion (LVO), and early arterial occlusion as one of the following: internal carotid
recanalisation is key to good clinical outcomes in AIS [5, artery (ICA), terminal ICA (T-lesion; T-occlusion), first and
6]. Recent guidelines by the Society of NeuroInterventional second segments of the middle cerebral artery (MCA M1,
Surgery (SNIS) state that age should not be used as a M2), tandem occlusion, basilar artery (BA), vertebral artery
contraindication for thrombectomy [7]. Despite this, a large (VA) or proximal posterior cerebral artery (PCA; [16]). The
multi-national survey of clinicians and interventionalists following data were collected: demographics, co-morbidities
found that age is one of the most important factors when (presence of hypertension, diabetes mellitus, dyslipidaemia,
a decision for EVT is made [8]. Moreover it is well reported ischemic heart disease, previous stroke and atrial fibrillation),
that older patients benefit less from EVT in general [6], and clinical variables including clinical severity of stroke
although, compared to those not treated with EVT, older as represented by the National Institute of Health Stroke
patients treated with EVT had significantly better func- Scale (NIHSS), mRS, subtype of ischemic stroke as per the
tional outcomes [6]. It is therefore important to further Trial of Org 10,172 in Acute Stroke Treatment (TOAST)
risk stratify and identify older patients who may derive classification and site of occlusion. All patients underwent
the most benefit from EVT, and differentiate them from acute neuroimaging using a computed tomography (CT)
those where EVT may not be beneficial and may even cause scan and CT angiography.
harm.
Although frailty is closely linked with age, age is not
the main contributor to frailty [2]. The prevalence of frailty Frailty
increases with age from 6% of those aged 60–64 years to Premorbid clinical frailty score (CFS) was collected for all
30% of those aged > 85 years [9, 10]. Clinically, frailty patients age ≥ 70 years admitted with AIS. The CFS is a
is associated with increased mortality, complications and well-validated, widely-used frailty tool in multiple clinical
longer hospital admissions [11]. One of the most commonly settings, and has been associated with clinical outcomes
used scoring systems for frailty is the Clinical Frailty Scale including mortality, functional decline, mobility and cog-
(CFS; [12]). Frailty has been shown to be a better predictor nitive decline [11]. It is an ordinal scale from 1 (very fit)
of clinical outcomes than age alone [2, 13]. Few studies have to 9 (terminally ill), that mixes items such as co-morbidity,
examined the relationship between frailty, stroke and stroke cognitive impairment and disability. All patients in this study
interventions such as EVT [14, 15]. Our study aimed to underwent routine geriatric assessment, which included the

2
 Effect of frailty on outcomes of endovascular treatment

collection of information on cognition, mobility and func- in Supplementary Figures 1 and 2, Supplementary data are
tion. CFS was scored retrospectively [17, 18] by an inde- available in Age and Ageing online.
pendent stroke nurse who was trained by a geriatrician. Ret-
rospective CFS scoring by trained personnel based on data Baseline characteristics and laboratory findings
from comprehensive geriatric assessments has been validated
with good reliability and accuracy [17, 18]. Patients with The mean age of frail patients was 80.4 (SD 5.9) years
CFS of 1–3 were defined as not frail, and CFS > 3 was and that of non-frail patients was 75.7 (SD 4.3) years
defined as frail in this study [12]. (P < 0.001). More frail patients were female than non-frail
patients (frail: 61.5%, 64 patients; non-frail 41.5%, 39
patients; P = 0.005). Frail patients were more likely to have
Primary and secondary outcomes hypertension (frail: 90.4%, 94 patients; non-frail 77.7%,
The primary outcome in this study was measured using the 73 patients; P = 0.014), atrial fibrillation (frail: 71.2%, 74
mRS at 90 days, which is a widely used clinical outcome patients; non-frail: 52.1%, 49 patients; P = 0.006), previ-

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

measure of functional independence post-stroke [6]. A mRS ous stroke or transient ischemic attack (TIA; frail: 21.2%,
of 0–2 was considered as good functional outcome. This 22 patients; non-frail: 8.6%, 8 patients; P = 0.014) and
was independently assessed by a qualified stroke neurologist cognitive impairment (frail: 18.3%, 19 patients; non-frail:
at 90-day follow-up. The secondary outcomes included the 4.3%, 4 patients; P = 0.002) than non-frail patients. There
following hospital outcomes: duration of hospitalisation, in- were no significant differences in racial distribution, diabetes
hospital mortality and carer requirement, and the follow- mellitus, dyslipidaemia, ischemic heart disease and smoking
ing stroke outcomes: successful reperfusion, symptomatic between the two groups. Patients who were frail had signifi-
intracranial haemorrhage (ICH) and haemorrhagic transfor- cantly lower haemoglobin (frail: 12.2 g/dl, SD 2.2; non-frail:
mation. The extent of angiographic reperfusion was evalu- 13.0 g/dl, SD 1.7; P = 0.005) and albumin (frail: 32.3 g/l,
ated according to the modified Thrombolysis in Cerebral SD 4.6; non-frail: 34.0 g/l, SD 4.0; P = 0.018). The baseline
Infraction (mTICI) grading system, and successful reperfu- characteristics and laboratory findings are shown in Table 1.
sion was defined as mTICI ≥ 2b. The presence of ICH was
determined by repeat brain imaging 22–36 h after treatment.
Stroke characteristics and treatment
There were no significant differences in median NIHSS
Statistical analysis on arrival between patients who were frail and not frail
Continuous variables were presented as mean ± standard (frail: median NIHSS 20, IQR 16–23; non-frail median
deviation (SD) and compared using Mann–Whitney U test NIHSS 18, IQR 13–23, P = 1.000; Table 1). According to
(non-parametric data) or Student’s t-test (parametric data). the TOAST classification, large artery atherosclerosis was
Categorical variables were presented as frequency and per- less common in frail patients (frail: 17.6%, 18 patients;
centages and compared using the Chi-square test or Fisher’s non-frail 33.0%, 30 patients, P = 0.014) and cardioembolic
exact test where appropriate. Adjusted analyses were per- stroke were more common in frail patients (frail: 70.6%,
formed using logistic regression to identify if frailty status 72 patients; non-frail 51.6%, 47 patients, P = 0.007). The
was independently associated with poor functional outcomes distribution in the sites of vessel occlusion were similar
in older stroke patients. The multivariable model included between patients who were frail and those who were not.
adjustment for age, NIHSS and median onset to puncture There were no significant differences in the proportion of
time, which were decided a priori to be significant predictors patients who received bridging thrombolysis between the
of functional outcomes from previous literature [19, 20]. All two groups (frail: 57.7%, 60 patients; non-frail: 62.8%, 59
statistical analyses were performed using SPSS version 25 patients; P = 0.467). There were no significant differences
(IBM Corp., Armonk, NY, USA). A P value of <0.05 was in procedure times, such as the median time from onset
considered statistically significant. to arrival, time from door to needle or time taken for clot
Ethics approval for this study was obtained from the local retrieval between the two groups (Table 1).
ethics review board (DSRB Reference 2021/00623).
Primary outcome
Results At 90 days, significantly fewer frail patients had mRS of
0 (frail: 4.8%, 5 patients; non-frail: 14.9%, 14 patients;
A total of 198 patients age ≥ 70 years who underwent EVT P = 0.016; Table 1). Achieving a good functional outcome
for AIS were included. The mean age was 78.1 (SD 5.7) at 90 days (mRS 0–2) was significantly less common in
years and 103 (52.0%) were female. The median CFS of frail patients (16.3%, 17 patients) than non-frail patients
this cohort was 4 (interquartile range [IQR] 3–4), and 94 (30.9%, 29 patients; P = 0.016). CFS as an ordinal variable
(47.5%) had CFS 1–3, whereas 104 (52.5%) had CFS > 3. was significantly associated with poor functional outcome
All patients had a premorbid mRS of 0–2 to qualify for (mRS 3–6) on univariate analysis (odds ratio [OR] 1.73;
EVT, and the distributions of mRS and CFS are shown 95% confidence interval [CI] 1.22–2.44; P = 0.002) and

3
B. Y. Q. Tan et al.

Table 1. Characteristics of frail and non-frail older acute ischaemic stroke patients that underwent endovascular
thrombectomy
Variable Not frail (CFS 1–3) n = 94 Frail (CFS > 3) n = 104 P value
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Baseline characteristics and investigations
Age (years), mean (SD) 75.7 (4.3) 80.4 (5.9) <0.001
Female, % (n) 41.5 (39) 61.5 (64) 0.005
Race, % (n)
Chinese 80.9 (76) 69.2 (72) 0.240
Malay 10.6 (10) 22.1 (23) 0.120
Indian 5.3 (5) 6.7 (7) 1.000
Others 3.2 (3) 1.9 (2) 1.000
Co-morbidities

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

Hypertension, % (n) 77.7 (73) 90.4 (94) 0.014
Diabetes mellitus, % (n) 30.9 (29) 35.6 (37) 0.481
Dyslipidaemia, % (n) 64.9 (61) 70.2 (73) 0.426
Ischaemic heart disease, % (n) 25.5 (24) 26.9 (28) 0.824
Smoking, % (n) 6.4 (6) 1.9 (2) 0.153
Atrial fibrillation, % (n) 52.1 (49) 71.2 (74) 0.006
Previous stroke/TIA, % (n) 8.6 (8) 21.2 (22) 0.014
Cognitive impairment, % (n) 4.3 (4) 18.3 (19) 0.002
NIHSS on arrival, median (IQR) 18 (13–23) 20 (16–23) 1.000
TOAST, % (n)
Large artery atherosclerosis 33.0 (30) 17.6 (18) 0.014
Cardioembolism 51.6 (47) 70.6 (72) 0.007
Small vessel occlusion 0 0 N/A
Stroke of other determined aetiology 0.0 (0) 1.0 (1) 1.000
Stroke of undetermined aetiology 15.4 (14) 2.0 10.8 (11) 0.342
Site of occlusion, % (n)
M1-MCA 48.9 (46) 49.0 (51) 0.989
M2-MCA 9.6 (9) 6.7 (7) 0.463
M3-MCA 3.2 (3) 2.9 (3) 1.000
Carotid T 16.0 (15) 22.1 (23) 0.272
Tandem 11.7 (11) 8.7 (9) 0.477
Basilar artery 8.5 (8) 9.6 (10) 0.787
Multi-vessel 2.1 (2) 1.0 (1) 0.605
Procedure timings
Time from onset to arrival (min), 85 (42–184) 73 (38–177) 0.355
median (IQR)
Time from door to imaging (min), 1 (0–12) 2 (0–13) 0.580
median (IQR)
Time from door to needle (min), 48 (40–57) 49 (42–59) 0.560
median (IQR)
Time from onset to puncture (min), 214 (165–308) 210 (161–310) 0.897
median (IQR)
Time taken for clot retrieval (min), 35 (21–58) 35 (20–60) 0.889
median (IQR)
Bridging thrombolysis, % (n) 62.8 (59) 57.7 (60) 0.467
Laboratory findings, mean (SD)
Creatinine (μmol/l) 94.3 (105.1) 111.5 (81.2) 0.198
Haemoglobin (g/dl) 13.0 (1.7) 12.2 (2.2) 0.005
Albumin (g/l) 34.0 (4.0) 32.3 (4.6) 0.018
Outcomes
Outcomes in hospital
Duration of hospitalisation (days), 15 (8–28) 15 (8–24) 0.539
median (IQR)
In-hospital mortality, % (n) 9.6 (9) 18.3 (19) 0.080
Carer required, % (n) 72.8 (59) 91.6 (76) 0.002
mRS at 3 months, % (n)
0 14.9 (14) 4.8 (5) 0.016
1 8.5 (8) 3.8 (4) 0.170
2 7.4 (7) 7.7 (8) 0.948
3 21.3 (20) 14.4 (15) 0.207
(Continued)

4
 Effect of frailty on outcomes of endovascular treatment

Table 1. Continued
Variable Not frail (CFS 1–3) n = 94 Frail (CFS > 3) n = 104 P value
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4 25.5 (24) 29.8 (31) 0.502
5 9.6 (9) 16.3 (17) 0.159
6 12.8 (12) 23.1 (24) 0.060
Stroke outcomes
Functional independence at 3 months 30.9 (29) 16.3 (17) 0.016
(mRS 0–2), % (n)
Successful reperfusion (mTICI ≥2b), % (n) 87.8 (79) 80.0 (80) 0.147
Symptomatic ICH, % (n) 5.3 (5) 2.9 (3) 0.481
Haemorrhagic transformation, % (n) 26.1 (24) 29.7 (30) 0.576
Abbreviations: CFS, Clinical Frailty Scale; ICH, intracerebral haemorrhage; IQR, interquartile range; MCA, middle cerebral artery; mRS, Modified Rankin Score;
mTICI, Modified Treatment in Cerebral Infarction; NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation; TIA, transient ischaemic attack;

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

TOAST, Trial of Org 10,172 in Acute Stroke Treatment. Bold: p < 0.05.

Figure 1. mRS at 3 months of frail and non-frail older stroke patients.

multivariable analysis adjusted for age, onset to puncture In the multivariable model, NIHSS was independently
time and NIHSS on arrival (adjusted OR [aOR] 1.54, associated with poor functional outcome (aOR 1.13; 95%
95% CI 1.04–2.28; P = 0.032). On ordinal shift analyses, CI 1.07–1.20; P < 0.001), but age (adjusted OR 1.04;
frailty was associated with an unfavourable shift in the mRS 95% CI 0.96–1.12; P = 0.331) and onset to puncture time
outcomes (OR 2.38; 95% CI 1.44–3.95; P = 0.001), which (adjusted OR 1.00; 95% CI 1.0–1.0; P = 0.817) was not
remained significant after adjusting for age, NIHSS and independently associated with the primary outcome. The
onset to puncture time (aOR 2.09; 95% CI 1.20–3.65; results of the multivariable analysis performed are shown in
P = 0.009). This is demonstrated in Figure 1. Table 2.

5
B. Y. Q. Tan et al.

Table 2. Univariate and multivariate analyses of predictors of poor functional outcomes in older stroke patients that
underwent EVT (n = 198)
Variables Univariate analysis Multivariate analysis

MRS 0–2 (n = 46) MRS 3–6 (n = 152) OR/Mean P value Adjusted OR P value
difference (95% CI) (95% CI)
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Age (years), mean (SD) 76.1 (5.2) 78.8 (5.7) 2.69 (0.84–4.53) 0.006 1.04 (0.96–1.12) 0.331
CFS, median (IQR) 3 (3–4) 4 (3–5) 1.73 (1.22–2.44) 0.002 1.54 (1.04–2.28) 0.032
Onset to puncture time 190 (145–310) 216 (168–310) 1.00 (1.00–1.00) 0.852 1.00 (1.00–1.00) 0.817
(mins), median (IQR)
NIHSS on arrival, 14 (10–20) 20 (16–23) 1.13 (1.07–1.20) <0.001 1.13 (1.07–1.20) <0.001
median (IQR)
Abbreviations: CFS, Clinical Frailty Scale; CI, confidence interval; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale; SD, standard

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

deviation. Bold: p <0.05.

Secondary outcomes Supplementary data are available in Age and Ageing online).
The median duration of hospitalisation (frail: 15 days, IQR Therefore, pre-stroke mRS as a measure of disability is not a
8–24; non-frail: 15 days, IQR 8–28; P = 0.539) were similar substitute for frailty assessment. There may be a segment of
between frail and non-frail patients. The in-hospital mortal- stroke patients who have no functional disability based on
ity trended towards being higher in frail patients than non- mRS, but who are frail and may have poorer outcomes with
frail patients, but did not reach statistical significance (frail: stroke interventions.
18.3%, 19 patients; non-frail: 9.6%, 9 patients; P = 0.080). The relationship between frailty and stroke is poorly
Other secondary outcomes including successful reperfusion understood with no clear consensus on the best methods
(mTICI ≥ 2b), symptomatic ICH and haemorrhagic to evaluate frailty in individuals with stroke or undergoing
transformation were similar between frail and non-frail stroke interventions [15]. Clinical frailty has been found
patients. Frail patients were more likely to require carers on to be well associated with poor functional outcomes, com-
discharge. Of the frail patients, 91.6% (76 patients) had carer plications and mortality in multiple healthcare settings and
requirement, whereas only 72.8% (59 patients) of specialties. Clinical frailty is associated with worse outcomes
non-frail patients required carers (P = 0.002). The results post-stroke or TIA. In a study of 15,468 patients, increase in
of the secondary outcomes are shown in Table 1. the Hospital Frailty Risk Score was associated with increased
length of stay, 90-day mortality, readmission and worse
health-related quality of life [22]. Other surrogate markers
Discussion of frailty, such as grip strength and walking speed were also
associated with poor recovery and survival post-stroke [23].
Our study demonstrated that (i) frailty as measured with Frail patients may also derive less benefit from hyperacute
CFS was associated with higher mRS scores at 90 days reperfusion therapies [15]. In 433 patients ≥ 75 years, Evans
post-EVT and (ii) the association with poorer functional et al. using frailty on CFS found that frailty was associated
outcomes remained significant after adjusting for age. As with higher 28-day mortality and reduced improvement in
only patients with premorbid mRS of 0–2 qualified for EVT, NIHSS post thrombolysis. Frailty measured by the Hospital
this suggested that frail patients were more likely to have Frailty Risk Score was associated with increased 90-day mor-
increased 90-day mRS post-EVT, and non-frail patients were tality and worse mRS after EVT in LVO stroke in two recent
more likely to show preserved functional outcome post-EVT. studies based in Germany [14, 24]. In this study, we used
Frailty as a state of vulnerability is a clinical syndrome the cut off of 70 years old, as expert consensus from 6 major
that overlaps with but is distinct from comorbidity and international, European and US societies recommend that
disability [21]. Although these conditions frequently co- all patients over the age of 70 years should be screened for
exist, not all frail patients are disabled, not all disabled frailty [2]. This age threshold was also used in various other
patients are frail, and not all comorbidities result in frailty or studies on frailty across different clinical settings [11, 25].
disability. This distinction is important, as it may be possible Similarly, we found that CFS was a significant predictor of
to attenuate or reverse frailty trajectories in order to reduce worse 90-day mRS post-EVT, and trended towards increased
its burden on health outcomes. Disability as measured by mortality, but did not reach statistical significance. This was
mRS is a familiar concept in stroke and is frequently used likely due to our study being underpowered for this outcome.
to determine eligibility for participation in stroke clinical The mechanisms behind the association of frailty with
trials and interventions. In our study, the distribution of poor post-EVT outcomes are manifold. Older patients had
baseline CFS was different from mRS, showing that they poorer EVT outcomes, and the prevalence of frailty increases
are distinct clinical entities (Supplementary Figures 1 and 2, with age [9]. The HERMES meta-analysis of 5 randomised

6
 Effect of frailty on outcomes of endovascular treatment

controlled trials found that the rates of good function out- Limitations
come at 90 days and mortality after EVT were 46 and 15% There were several limitations to this study. First, this was
respectively in the general trial population, in contrast to 30 a single-centre retrospective cohort study. Hence, causation
and 28% in those above the age of 80 years [6]. A meta- could not be established, and there may be unidentified
analysis of 16 studies on those aged >80 years found lower confounding factors in the association between CFS and
success of therapy (OR 0.72), worse functional outcomes clinical outcomes post-EVT. As data was collected from a
(OR 0.40) and higher mortality (OR 2.26) than those single tertiary centre, results may not be generalisable to
<80 years old [19]. Although we found that frail patients other populations. CFS was also computed retrospectively
were significantly older, frailty remained significantly asso- based on routine geriatric assessment that included infor-
ciated with poor functional outcomes after adjustment for mation on cognition, mobility and function, which may be
age, confirming the findings of Evans et al. in a population susceptible to inaccuracies in the interpretation of data not
post-thrombolysis [15]. Age was associated with poor func- primarily intended for CFS calculation. However, retrospec-
tional outcomes on univariate analysis but not after adjust- tive CFS scoring has been validated with good reliability and

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

ing for CFS, NIHSS and time to puncture in our study, accuracy [17, 18]. Second, this study included 198 patients
suggesting that CFS may be a better predictor of worse mRS and may be underpowered for the survival outcome, there-
than age alone. Further prospective studies are needed to fore concrete conclusions cannot be drawn. Third, we only
validate this finding and investigate the performance of CFS investigated short-term outcomes up to 90 days, therefore
as one of the factors in determining suitability for EVT in the differences in long-term outcomes are unknown. We
the clinical setting. adopted the commonly used clinical outcomes in stroke
Frailty has been associated with increased stroke severity trials, including 90-day mRS [6], facilitating comparisons
measured by the NIHSS. A prospective study on 232 with previous literature.
patients found that frailty was not associated with short-term
outcomes after adjustments for NIHSS and length of stay,
therefore stroke severity may mediate the effect of frailty on
Conclusions
stroke outcomes. However, this study excluded patients with
pre-existing disability (mRS ≥ 3), and therefore reported In this study, we demonstrated that frailty was associated
a lower proportion of frail patients of 12%, which may with higher mRS scores at 90 days post-EVT in those
have introduced significant selection bias. NIHSS is an ≥70 years, independently of age, NIHSS and time to inter-
independent predictor of poor stroke outcomes in older vention. Frail patients were more likely to have increased 90-
adults, and NIHSS ≥ 16 was correlated with poor prognosis day mRS post-EVT, and non-frail patients were more likely
post-EVT in one study [20]. NIHSS may be combined with to show preserved functional outcome post-EVT. Elucidat-
age in the SPAN index (Stroke Prognostication using Age ing how frailty predicts clinical and functional outcomes
and NIHSS Stroke Scale), and a combined score of ≥100 in stroke can lead to better prognostication and decision-
had significantly lower favourable outcomes after EVT [26]. making. Further prospective studies are needed to evaluate
In contrast, other studies found an independent effect of the use of frailty screening tools in stroke patients and
frailty after adjustment for NIHSS, age and vascular risk optimising patient selection for EVT.
factors [14, 15]. In our study, CFS remained independently
associated with poor functional outcomes after adjusting
for NIHSS, age and onset to puncture time, although
the effect size was reduced. Furthermore, the NIHSS on Supplementary Data: Supplementary data mentioned in
arrival was similar between frail and non-frail patients, the text are available to subscribers in Age and Ageing online.
which confirmed the findings of another study using CFS in Declaration of Conflicts of Interest: None.
patients ≥ 75 years [15].
Complications of EVT and AIS include symptomatic Declaration of Sources of Funding: None.
ICH and haemorrhagic transformation, however studies on
these outcomes and frailty are limited. There were no signifi-
References
cant differences in risk of symptomatic ICH in octogenarians
post-EVT in a meta-analysis of 16 studies [19]. One study
using the Hospital Frailty Risk Score found no significant 1. Feigin VL, Stark BA, Johnson CO et al. Global, regional, and
national burden of stroke and its risk factors, 1990-2019: a
differences in ICH and periprocedural subarachnoid haem-
systematic analysis for the Global Burden of Disease Study
orrhage among different frailty groups [24]. Similarly, our 2019. Lancet Neurol 2021; 20: 795–820.
study found no significant differences in symptomatic ICH 2. Morley JE, Vellas B, van Kan GA et al. Frailty consensus: a call
and haemorrhagic transformation between frail and non-frail to action. J Am Med Dir Assoc 2013; 14: 392–7.
patients, suggesting that frailty may have smaller impacts 3. Tan BYQ, Tan JTC, Cheah D et al. Long-term trends in
on these complications, but further research is needed to ischemic stroke incidence and risk factors: perspectives from
confirm these findings. an Asian stroke registry. J Stroke 2020; 22: 396–9.

7
B. Y. Q. Tan et al.

4. Palmer K, Vetrano DL, Padua L et al. Frailty syndromes in 17. Davies J, Whitlock J, Gutmanis I et al. Inter-rater reliability
persons with cerebrovascular disease: a systematic review and of the retrospectively assigned clinical frailty scale score in a
meta-analysis. Front Neurol 2019; 10: 1255–5. geriatric outreach population. Can Geriatr J 2018; 21: 1–5.
5. Rha J-H, Saver JL. The impact of recanalization on ischemic 18. Stille K, Temmel N, Hepp J et al. Validation of the clinical
stroke outcome. Stroke 2007; 38: 967–73. frailty scale for retrospective use in acute care. Eur Geriatr Med
6. Goyal M, Menon BK, van Zwam WH et al. Endovascular 2020; 11: 1009–15.
thrombectomy after large-vessel ischaemic stroke: a meta- 19. Zhao W, Ma P, Zhang P et al. Mechanical thrombectomy
analysis of individual patient data from five randomised trials. for acute ischemic stroke in octogenarians: a systematic review
The Lancet 2016; 387: 1723–31. and meta-analysis [systematic review]. Front Neurol 2020; 10:
7. Mokin M, Ansari SA, McTaggart RA et al. Indications for 1355.
thrombectomy in acute ischemic stroke from emergent large 20. Sharobeam A, Cordato DJ, Manning N et al. Functional out-
vessel occlusion (ELVO): report of the SNIS standards and comes at 90 days in octogenarians undergoing Thrombectomy
guidelines committee. J NeuroInterv Surg 2019; 11: 215. for Acute Ischemic Stroke: a prospective cohort study and
8. Saposnik G, Menon BK, Kashani N et al. Factors associated meta-analysis [brief research report]. Front Neurol 2019; 10:

Downloaded from https://academic.oup.com/ageing/article/51/4/afac096/6575882 by guest on 02 March 2024

with the decision-making on endovascular Thrombectomy for 254.
the Management of Acute Ischemic Stroke. Stroke 2019; 50: 21. Fried LP, Ferrucci L, Darer J et al. Untangling the concepts of
2441–7. disability, frailty, and comorbidity: implications for improved
9. Siriwardhana DD, Hardoon S, Rait G et al. Prevalence of targeting and care. J Gerontol A Biol Sci Med Sci 2004; 59:
frailty and prefrailty among community-dwelling older adults 255–63.
in low-income and middle-income countries: a systematic 22. Kilkenny MF, Phan HT, Lindley RI et al. Utility of the
review and meta-analysis. BMJ Open 2018; 8: e018195. hospital frailty risk score derived from administrative data
10. Tan LF, Lim ZY, Choe R et al. Screening for frailty and and the association with stroke outcomes. Stroke 2021; 52:
sarcopenia among older persons in medical outpatient clinics 2874–81.
and its associations with healthcare burden. J Am Med Dir 23. Winovich DT, Longstreth WT Jr, Arnold AM et al. Factors
Assoc 2017; 18: 583–7. associated with ischemic stroke survival and recovery in older
11. Church S, Rogers E, Rockwood K et al. A scoping review of adults. Stroke 2017; 48: 1818–26.
the clinical frailty scale. BMC Geriatr 2020; 20: 393. 24. Schnieder M, Bähr M, Kirsch M et al. Analysis of frailty in
12. Rockwood K, Song X, MacKnight C et al. A global clinical geriatric patients as a prognostic factor in endovascular treated
measure of fitness and frailty in elderly people. Can Med Assoc patients with large vessel occlusion strokes. J Clin Med 2021;
J 2005; 173: 489. 10: 2171.
13. Joseph B, Pandit V, Zangbar B et al. Superiority of frailty over 25. Fallon A, Kilbane L, Briggs R et al. Screening for frailty in
age in predicting outcomes among geriatric trauma patients: older emergency department patients: the utility of the survey
a prospective analysis. JAMA Surg 2014; 149: 766–72. of health, ageing and retirement in Europe frailty instrument.
14. Pinho J, Küppers C, Nikoubashman O et al. Frailty is an QJM 2017; 111: 151–4.
outcome predictor in patients with acute ischemic stroke 26. Almekhlafi MA, Davalos A, Bonafe A et al. Impact
receiving endovascular treatment. Age Ageing 2021; 50: of age and baseline NIHSS scores on clinical outcomes
1785–91. in the mechanical Thrombectomy using solitaire FR in
15. Evans NR, Wall J, To B et al. Clinical frailty independently acute ischemic stroke study. Am J Neuroradiol 2014; 35:
predicts early mortality after ischaemic stroke. Age Ageing 1337–40.
2020; 49: 588–91.
16. Yeo LL-L, Chen VHE, Leow AS-T et al. Outcomes in young
adults with acute ischemic stroke undergoing endovascular
thrombectomy: a real-world multicenter experience. Eur J Received 22 December 2021; editorial decision 4 March
Neurol 2021; 28: 2736–44. 2022