Long-term outcomes of acute ischemic stroke patients treated with ...

Journal of the Neurological Sciences 390 (2018) 77–83

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Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns

Long-term outcomes of acute ischemic stroke patients treated with endovascular thrombectomy: A real-world experience

T

Wenbo Zhaoa, Shuyi Shanga, Chuanhui Lib, Longfei Wua, Chuanjie Wua, Jian Chenb, ⁎ ⁎⁎ Haiqing Songa, Hongqi Zhangb, Yunzhou Zhanga, Jiangang Duanc, , Wuwei Fengd, Xunming Jib, a

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China c Department of Emergency, Xuanwu Hospital, Capital Medical University, Beijing, China d Department of Neurology, Medical University of South Carolina, Charleston, USA b

A R T I C LE I N FO

A B S T R A C T

Keywords: Acute stroke Thrombectomy Treatment outcome Large artery atherosclerosis Cardioembolism

Background and purpose: Long-term follow-up of large trials have confirmed the superiority of endovascular thrombectomy (ET) for treating acute ischemic stroke (AIS). However, it is still unknown whether these results can be generalized to clinical practice. In this study, we aimed to determine the long-term outcomes of AIS postET in the real-world clinical practice. Methods: This observational study is based on a single-center prospective registry study. AIS patients were treated with second-generation stent retrievers from December 2012 to April 2016. The primary outcome was modified Ranks scale (mRS) at the time of the latest assessment. Favorable outcome was defined as mRS scores 0–2, and the unfavorable outcome was defined as mRS scores 3–6. Results: Eighty-nine AIS subjects with large artery occlusion in anterior circulation undergoing ET were eligible for analysis. Median follow-up duration was 20 months (interquartile range 6–32), and 47 subjects (53%) achieved favorable outcome whereas 17 subjects (19%) were functional dependence and 25 subjects (28%) died. Independent predicators for long-term unfavorable outcome were higher baseline National Institutes of Health Stroke Scale (NIHSS) score (odd ratio:1.21;95% confidence interval 1.09–1.35; p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (odd ratio:16.45;95% confidence interval 1.34–193.44; p = 0.026). More subjects of large-artery-atherosclerosis underwent permanent intracranial stenting (22%vs.10%) as compared with those of cardioembolism, while subjects of cardioembolism were more likely to experience sICH (13% vs.8%) and died (32%vs.16%). Conclusions: Over half of AIS patients can achieve favorable long-term outcomes post-ET. Higher baseline NIHSS scores and sICH are independently associated with unfavorable outcome. Overall, clinical practice in this single canter can replicate the long-term outcomes from the published endovascular clinical trials.

1. Introduction Endovascular thrombectomy (ET) using a second-generation stent retriever device for acute ischemic stroke (AIS) has been considered as the standard endovascular management for patients with proximal large artery occlusion in the anterior circulation [1,2]. Several large studies have concluded the superiority of ET by demonstrating more patients having the functional independence at 3 months post-treatment [3]. More recently, REVASCAT and MR CLEAN studies reported favorable long-term outcome at 1 and 2 years post-treatment respectively [4,5]. However, whether these outcomes from randomized trials

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can be generalized to real-world clinical practice is still unknown. In developing country like China, stroke is the leading cause of death and adult disability. ET has been adopted in several major academic centers for several years and become much more popular after the publication of these landmark studies. No center in China has participated in the trials above. More importantly, the etiology of large artery atherosclerosis (LAA) is more common than cardioembolism in Chinese AIS patients [6,7], and approximately half of them have intracranial artery stenosis [8]. Recently, ACTUAL study, a multicenter registry program in China, reported that 43.6% patients could achieve functional independence at 90 days after ET, but the long-term

Correspondence to: J. Duan, Department of Emergency, Xuanwu Hospital, Capital Medical University, No 45, Changchun Street, Xicheng District, Beijing, 100053, China. Correspondence to: X. Ji, Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, No 45, Changchun Street, Xicheng District, Beijing, 100053, China. E-mail addresses: [email protected] (J. Duan), [email protected] (X. Ji).

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https://doi.org/10.1016/j.jns.2018.03.004 Received 21 December 2017; Received in revised form 27 February 2018; Accepted 1 March 2018 Available online 04 March 2018 0022-510X/ © 2018 Elsevier B.V. All rights reserved.


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on the following outcomes: a) survival status; b) date of death in those who died; c) mRS at the time of assessment; d) recurrent stroke; e) poststroke seizure; f) use of medications in 2 categories (i.e., antithrombotic agents and statins). The protocol was approved by the Ethic Committee of Xuanwu Hospital of Capital Medical University (study permit number: [2017] 030). All subjects or their legally authorized representatives provided written informed consent at the time of admission to our hospital.

functional outcomes of this patient population is still unclear [9]. Therefore, information about the safety and long-term efficacy of second-generation stent retriever in this stroke population in real-world practice is lacking. In this study, we aimed to assess the long-term outcome of AIS after ET, identify risk factors for long-term unfavorable outcome, and investigate differences between patients due to LAA and cardioembolism. 2. Methods

2.3. Endpoints 2.1. Study population The primary outcome was mRS at the time of the latest assessment. The secondary outcomes were: 1) risk factors for long-term unfavorable outcomes (mRS > 2); 2) comparisons between AIS subjects due to LAA and cardioembolism; 3) any cause of death; 4) post-stroke seizure and recurrent stroke.

The Xuanwu Stroke Center program of our center includes a prospective registry for the study of revascularization therapy (i.e. intravenous thrombolysis and endovascular treatment) for AIS. ET has been applied according to the guidelines with the intention to start the procedures as soon as possible after the symptoms onset [10–12]. All potential patients were initially evaluated by a stroke neurologist. The National Institutes of Health Stroke Scale (NIHSS) and other scales including the 3-Item Stroke Scale (3-ISS), the Los Angeles Motor Scale (LAMS) were used to identified potential patients with large vessel occlusion. Subjects for intravenous thrombolysis or ET underwent emergency non-contrast head CT first. CT perfusion or head and neck CT angiography (CTA) was not mandatory. According to the local catheter laboratory regulations, interventionists, who has been practicing interventional neuroradiology for > 5 years and able to perform extracranial and intracranial stents proficiently, were qualified to perform endovascular treatment for AIS patients after systematic training. Local or general anesthesia was chosen according to the level of patient cooperation and the medical condition of the patient. All procedures were performed via a transfemoral approach. Intravenous heparin to maintain the activated clotting time ranged 250 to 300 s during the procedure was mandatory, except subjects treated with intravenous alteplase. The type and size of stent-retriever, other necessary devices (e.g., guide wires and catheters), and strategies of intervention were left to the discretion of the interventionists. All subjects had a follow-up head CT 12 to 24 h after the ET. Transcranial color Doppler (TCCD) ultrasound was scheduled to be performed between 24 and 72 h. For subjects who do not have contraindication or are capable to have CTA or magnetic resonance angiography (MRA), they will be done before discharge. For each subject, the baseline characteristics, functional outcomes, complications, and follow-up outcomes were entered in the registry. For the present study, all subjects treated with ET using a secondgeneration stent-retrievers from December 2012 to April 2016 were selected. Eligibility criteria for the present study were: 1) AIS caused by a proximal large artery occlusion in the anterior circulation and treated with ET using second-generation stent-retrievers between December 2012 and April 2016, and 2) availability and accessibility of information on long-term outcomes.

2.4. Statistical methods The first step of the analysis was to compare age, sex, baseline NIHSS, the location of occluded artery, time from onset to recanalization, and sICH between subjects with and without available data of long-term outcomes. We analyzed the data of subjects with the longterm outcomes as the second step. Long-term outcome was dichotomized as the favorable outcome (mRS score of 0–2) and the unfavorable outcome (including death and mRS score of 3–5). Baseline characteristics were compared between subjects with favorable outcomes and unfavorable outcomes. Binary logistic regression was performed with long-term unfavorable outcome or not as the dependent variate and with the age, baseline NIHSS, atrial fibrillation, diabetes mellitus, sICH, stroke etiology, ASPECTS, Thrombolysis in Cerebral Infarction (TICI) scores, and onset to reperfusion time as the covariates. Kaplan-Meier survival probability estimate was calculated to detect the recurrent stroke and survival probability, and Kaplan-Meier curves were made with the Prism 6.0 statistical program (GraphPad Software). For continuous data, mean ± standard deviation (SD) or median (interquartile range, IQR) was used to summarize data; t-test for independent samples or Mann-Whitney U Tests was performed to detect differences between groups. For binary data, frequency or percentage was used to summarize data, between-group comparisons were performed via the Chi-square or Fisher's exact test when appropriate. All data were analyzed using SPSS 19.0 (IBM Inc.) with the significance level of p < 0.05 (two sides). 3. Results From December 2012 to April 2016, a total of 99 consecutive AIS subjects with proximal large artery occlusion in the anterior circulation were treated with the second-generation stent-retrievers. After excluding 10 subjects without long-term outcomes, this study consisted of 89 subjects (90%) and they did not differ from the excluded 10 subjects in age (p = 0.410), sex (p = 0.925), baseline NIHSS (p = 0.128), location of occluded artery (p = 0.295), time from onset to recanalization (p = 0.579), and sICH (p = 0.680) (Table 1).

2.2. Data collection We used the following variables of subjects from the database: age, sex, the location of occluded artery, time from onset to puncture and recanalization, initial stroke severity assessed by NIHSS, initial CT examination evaluated by Alberta Stroke Program Early CT Score (ASPECTS), blood pressure, emergency laboratory tests and blood pressure, cerebrovascular diseases risk factors, etiology according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST), operation details, symptomatic intracerebral hemorrhage, post-stroke seizure, recurrent ischemic cerebrovascular event, global outcomes at 3 months, 1 year and 2 years assessed by modified Rankin Scale (mRS). Long-term outcomes were ascertained by telephone interviews and/ or clinic visits. Two stroke neurologists contacted or interviewed with all subjects and/or their family members to collect medical information

3.1. Baseline characteristics and follow-up duration Baseline characteristics of all 89 subjects were summarized in Table 2. The average age was 61.2 ± 13.9 years old, and 56 subjects (63%) were male. Baseline NIHSS score was 16.0 (13.0–21.5), ASPECTS was 8.0 (7.0–9.0), time from onset to groin puncture and recanalization were 291 (219–361) minutes and 386 (313–439) minutes respectively. Among all the subjects, 25 subjects (28%) were treated with intravenous alteplase prior to ET, 14 subjects (16%) were treated with additional intra-arterial thrombolysis, 15 subjects (17%) were treated 78


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Table 1 Comparison of demographic and clinical characteristics between patients with and without long-term outcomes. All patients N = 99

With long-term outcome N = 89

Without long-term outcome N = 10

P value

Age at onset, mean ± SD Female, n (%) NIHSS, median (IQR)

61.6 ± 13.7 63 (64%) 16.0 (12.0–20.0)

61.2 ± 13.9 56 (63%) 16.0 (13.0–21.5)

65.0 ± 11.2 7 (70%) 14.5 (10.75–17.25)

0.410 0.925 0.128

Location of occluded artery ICA, n (%) MCA, n (%) Time from onset to recanalization, median (IQR) sICHa, n (%)

40 (40%) 59 (60%) 392.0 (314.0–453.5) 11 (11%)

38 (43%) 51 (57%) 386.0 (313.25–439.25) 9 (10%)

2 (20%) 8 (80%) 395.0 (312.5–487.25) 2 (20%)

0.295 0.295 0.579 0.680

SD, standard deviation; NIHSS, National Institutes of Health Stroke Scale; IQR, interquartile range; ICA, internal carotid artery; MCA, middle cerebral artery; sICH, symptomatic intracerebral hemorrhage. a sICH were defined according to the ECASS III trial definitions. Table 2 Demographic and clinical characteristics. All patients N = 89

Favorable outcome N = 47

Unfavorable outcome N = 42

p value

Age at onset, mean ± SD Male, n(%) NIHSS, median (IQR) ASPECTS, median (IQR) Treatment with IV alteplase, n(%) OTP time, median (IQR) OTR time, median (IQR) SBP, mean ± SD Length of follow up, median (IQR)

61.2 ± 13.9 56 (63%) 16.0 (13.0–21.5) 8.0 (7.0–9.0) 25 (28%) 291 (219–361) 386 (313–439) 141.0 ± 26.1 20 (6–32)

58.3 ± 13.0 33 (70%) 14.0 (11.0–18.0) 8.0 (7.0–9.0) 15 (32%) 260 (207–360) 385 (315–430) 136.2 ± 25.2 27 (19–25)

64.5 ± 14.3 23 (55%) 20.0 (16.0–25.0) 8.0 (6.0–8.0) 10 (24%) 295 (230–365) 387.0 (311–475) 146.4 ± 26.73 5 (3–26)

0.033 0.132 < 0.001 0.527 0.396 0.702 0.672 0.065 < 0.001

Laboratory test (mean ± SD) Glucose LDL HCY

8.08 ± 3.49 2.47 ± 1.01 12.87 ± 6.21

7.30 ± 3.13 2.40 ± 1.12 12.39 ± 5.25

8.95 ± 3.70 2.57 ± 0.86 13.53 ± 7.38

0.026 0.432 0.471

Vascular risk factors (n,%) Hypertension Diabetes mellitus Atrial fibrillation Smoking CHD

49 17 34 26 18

(55%) (19%) (38%) (29%) (20%)

21 (45%) 6 (13%) 14 (30%) 15 (32%) 8 (17%)

28 11 20 11 10

0.037 0.108 0.084 0.553 0.426

(67%) (26%) (482%) (26%) (24%)

Stroke Etiology, n(%) Large artery atherosclerosis Cardioembolism Other Undermined Occlusion vessels MCA ICA Tandem occlusions

49 (55%) 31 (35%) 2 (2%) 7 (8%)

29 (62%) 14 (30%) 1 (2%) 3 (6%)

20 (48%) 17 (40%) 1 (2%) 4 (10%)

51 (57%) 33 (37%) 5 (6%)

27 (57%) 17 (36%) 3 (7%)

24 (57%) 16 (38%) 2 (5%)

0.182 0.291 1.000 0.900 0.939 – – –

Procedure Details(n,%) General anesthesia Tirofiban Additional intra-arterial thrombolysis Permanent intracranial stenting TICI = 0 TICI = 2b/3 sICHa, n(%)

55 (62%) 29 (33%) 14 (16%) 15 (17%) 9 (10%) 73 (82%) 9 (10%)

29 (62%) 17 (36%) 7 (15%) 9 (19%) 5 (11%) 40 (85%) 1 (2%)

26 (61%) 12 (29%) 7 (17%) 6 (14%) 4 (10%) 33 (78%) 8 (19%)

0.984 0.445 0.819 0.541 0.862 0.423 0.008

SD: standard deviation; IQR: interquartile range; NIHSS: National Institutes of Health Stroke Scale; ASPECTS: Alberta Stroke Program Early CT score; OTP: onset to groin puncture; OTR: onset to recanalization; LDL: low density lipoprotein, HCY: homocysteine; SBP: systolic blood pressure; ICA: internal carotid artery; MCA: middle cerebral artery; CHD: coronary heart disease; IV: intravenous; MCA: middle cerebral artery; ICA: internal carotid artery; TICI: Thrombolysis in Cerebral Infarction; sICH: symptomatic intracerebral hemorrhage. a sICH were defined according to the ECASS III trial definitions.

clinical visit (which came later) was 20 months (range 1–52 months, IQR 6–32 months). The follow-up periods of subjects who died were recorded as from stroke onset to the time that he/she died. Therefore, the follow-up periods of 23 subjects (26%) were < 12 months, and other 66 subjects (74%) were longer than 12 months including 38 subjects (43%) whose follow-up period ≥24 months.

with permenant intracranial stenting, and 29 subjects (33%) were treated with tirofiban during and after the ET procedures. Occluded arteries failed to be recanalized in 9 subjects (10%), 73 subjects (82%) achieved good perfusion (TICI score 2b or 3), and 12 subjects (13%) suffered from sICH. Other baseline data, including emergency laboratory tests, the location of occluded artery, vascular risk factors, and stroke etiology were also shown in Table 2. The median time interval from ET to the last telephone interview/

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Fig. 1. Distribution of functional scores at 3 months and long-term follow-up. mRS: modified Rankin scale. Shown are scores on the mRS for all subjects.

3 months after ET. After that, 2 subjects died 5 months after ET, and the other 3 subjects died in 7, 18 and 21 months after ET respectively. Causes of death were fatal stroke in 20 subjects (80%), cardiac diseases in 1 subject (4%), pneumonia in 2 subjects (8%), recurrent stroke in 1 subject (4.0%), and suicide in 1 subject (4%). Life table survival analysis indicated that the cumulative proportion surviving was 75% after 3 months, 74% after 6 months, 73% after 18 months, and 70.9% after 51 months (Fig. 2A).

3.2. Primary outcome At the time of follow-up, 47 subjects (53%) achieved functional independence (mRS scores 0–2), 17 subjects (19%) were functionally dependent (mRS scores 3–5), and 25 subjects (28%) died. Compared with the outcome at 3 months, the proportion of subjects with the favorable long-term outcome (mRS scores 0–2) or death (mRS score 6) was slightly higher (53% vs. 48% and 28% vs. 22% respectively), whereas the proportion of subject with moderate to severe disability (mRS scores 3–5) was lower (19% vs. 30%) (Fig. 1).

3.3.3. Post-stroke seizure and recurrent stroke During the follow-up period, 3 subjects (3%) had post-stroke seizures, and 8 subjects (9%) suffered from recurrent ischemic strokes with 1 subjects (1%) within 3 months, 4 subjects (4%) within 6 months, 5 subjects (6%) within 12 months, 6 subjects (7%) within 24 months. Life table survival analysis indicated that the cumulative proportion of recurrent stroke was 4% after 3 months, 7% after 12 months, 9% after 18 months, 11% after 42 months, and 27% after 51 months (Fig. 2B).

3.3. Secondary outcomes 3.3.1. Long-term favorable outcome versus unfavorable outcome Results of univariate analysis of baseline data for favorable and unfavorable long-term outcomes are shown in Table 2. Among subjects with the long-term unfavorable outcome, the age, NIHSS score at admission and emergency plasma glucose level were significantly higher than subjects with favorable outcome, whereas the length of follow-up was significantly shorter than that of subjects with favorable outcome (Table 2, p < 0.05 each). Multivariate regression analysis showed that higher baseline NIHSS scores (OR: 1.21; 95% CI 1.09–1.35, p < 0.001) and sICH (OR: 16.45; 95% CI 1.34–193.44 p = 0.026) were independently associated with long-term unfavorable outcome (Table 3).

3.3.4. LAA versus cardioembolism Among all subjects, the etiology of stroke was LAA in 49 subjects and cardioembolism in 31 subjects. Comparisons of the baseline characteristics, operation details and 3-month outcome between the two groups were summarized in Table 4. Compared with subjects of cardioembolism, age at onset and ASPECTS were much lower in subjects of LAA (p < 0.05 each). The time from groin puncture to recanalization is much longer in the LAA group (median 90.0 vs. 81.0 min, p = 0.065). The proportion of subject treated with tirofiban (39% vs. 23%) and permanent intracranial stenting (22% vs. 10%), and failure of recanalizing the occlude artery (12% vs. 6%) in the LAA group were twice as many as that in the cardioembolism group, but no significant difference was detected (p > 0.5 each). The incidence of sICH (13% vs. 8%, p = 0.760) and the 3-month mortality (32% vs. 16%, p = 0.096) in the cardioembolism group were twice as many as the LAA group, while the proportion of subject of functional independence (45% vs. 51%) and functional dependence (23% vs. 33%) were not statistically significant difference.

3.3.2. Mortality and cause of death Among all subjects, 25 subjects (28%) died at the time of follow-up. 13 of 25 subjects (52%) died within 7 days after ET, 18 subjects (72%) died within 4 weeks after ET, and 20 subjects (80%) died within Table 3 Multivariate analysis of long-term outcomes. Variates

OR

95% CI

p

Age at onset NIHSS Atrial fibrillation Diabetes Mellitus TOASTa ASPECT score TICI Onset to recanalization time sICH

1.03 1.21 1.75 3.25 1.13 0.71 0.71 1.00 16.45

0.98–1.08 1.09–1.35 0.49–6.189 0.74–14.41 0.59-2.18 0.44–1.15 0.41–1.21 0.99–1.01 1.34–193.44

0.220 < 0.001 0.387 0.120 0.708 0.167 0.707 0.614 0.026

4. Discussion In this observational study about the long-term outcomes of AIS patients with large artery occlusion in the anterior circulation and treated with ET, we found that after a median follow-up period of 20 months, 53% of AIS subjects were functional independence whereas 19% subjects were functional dependence and 28% had died. Higher baseline NIHSS scores and sICH were the independent predicators of the long-term unfavorable outcome. Operation techniques and prognosis might be different between AIS patients due to LAA and cardioembolism in etiology. And Technical skills improved as the number of AIS

OR: odd ratio; CI: confidence interval; NIHSS: National Institutes of Health Stroke Scale; TOAST: Trial of Org 10,172 in Acute Stroke Treatment; ASPECTS: Alberta Stroke Program Early CT score; TICI: Thrombolysis in Cerebral Infarction; sICH: symptomatic intracerebral hemorrhage. a TOAST included four types: large artery atherosclerosis, cardioembolism, other, and undetermined. And it was analysis as a multiple categorical covariate. 80


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Fig. 2. Kaplan Meier estimate of survival probability (A) and recurrent stroke probability (B). Table 4 Stroke due to LAA versus cardioembolism.

Age at onset, mean ± SD Male, n(%) NIHSS, median (IQR) ASPECTS, median (IQR) Treatment with IV alteplase, n (%) Time from groin puncture to recanalization, min, median (IQR) Operation details, n (%) Treatment with Tirofiban Additional intra-arterial thrombolysis Permanent intracranial stenting TICI = 0 TICI = 2b/3 3-months outcome, n (%) sICH Death Functional independence (mRS scores 0–2) Functional dependence (mRS scores 3–5)

Table 5 Studies regarding the long-term outcome in AIS Subjects treated with ET.

Atherosclerosis N = 49

Cardioembolism N = 31

p value

Variable

This Study N = 89

REVASCAT N = 103

MR CLEAN N = 233

59.5 ± 13.3 33 (67%) 16.0 (12.5–19.5) 8.0 (7.0–8.5) 15 (31%)

66.3 ± 13.0 18 (58%) 17.0 (13.0–25.0) 8.0 (8.0–9.0) 9 (29%)

0.029 0.400 0.287 0.016 0.881

Age, mean ± SD/median (IQR)

61.2 ± 13.9

65.7 ± 11.3

NHISS, median (IQR)

90 (64–142)

81 (45–100)

0.065

16.0 (13.0–21.5) 8.0 (7.0–9.0) 292 (220–361) 386 (313–439) 28%

17.0 (14.0–20.0) 7.0 (6.0–9.0) 269 (201–340) 355 (269–430) 68.0%

65.8 (54.5–76.0) 17 (14–21) 9 (7–10) 260 (210−313) NA

16%

1%

10.3%

17%

1%

NA⁎

33% 10%

0 4.9%

0 7.7%

Post-procedure TICI score (%) 0 1 2a 2b 3

10% 2% 6% 44% 38%

7.8% 2.0% 24.5% 47.1% 18.6%

13.8% 5.6% 21.9% 34.7% 24.0%

3-months outcome, (%) Death Functional independence Functional dependence Recurrent stroke

22% 48% 30% 1%

18.4% 43.7% 37.9% 3.9%

21.0% 33.0% 46.0% NA

1-year outcome (%) Death Functional independence Functional dependence

26% 53% 21%

23.0% 44.0% 32.0%

– – –

2-year outcome (%) Death Functional independence Functional dependence Recurrent stroke

28% 53% 19% 7%

– – – –

26.0% 37.1% 36.9% 1.0%

19 (39%) 7 (14%)

7 (23%) 4 (13%)

0.132 0.861

11 (22%)

3 (10%)

0.143

6 (12%) 38 (78%)

2 (6%) 26 (84%)

0.646 0.491

4 (8%) 8 (16%) 25 (51%)

4 (13%) 10 (32%) 14 (45%)

0.760 0.096 0.610

16 (33%)

7 (23%)

0.332

ASPECTS, median (IQR) Time from onset to groin puncture, median (IQR) Time from onset to recanalization, median (IQR) Treatment with intravenous alteplase, (%) Treatment with additional intraarterial thrombolysis, (%) Treatment with permanent intracranial stenting, (%)⁎ Treatment with Tirofiban, (%) sICH, (%)

LAA: large artery atherosclerosis; SD: standard deviation; IQR: interquartile range; NIHSS: National Institutes of Health Stroke Scale; ASPECTS: Alberta Stroke Program Early CT score; TICI: Thrombolysis in Cerebral Infarction; sICH: symptomatic intracerebral hemorrhage; mRS: modified Rankin scale.

patients treated with ET increased, as a result, the time from groin puncture to recanalization was reduced accordingly. Intriguingly, after 3 months, the rate of favorable outcome increased by 5% at long-term follow-up, which is in consistent with previous studies [4,13,14]. Generally, recovery after stroke is determined by the initial stroke severity, those with mild or moderate disability tend to recover within 2–3 months, but the recovery of those with severe disability may take longer to recover or unable to recover [15,16]. In this study, baseline NIHSS scores of most stroke are higher than 10 points, and this may be why the rate of favorable outcome is higher at longterm than 3 months. Just as previous studies about ET or intravenous thrombolysis for AIS [17,18], this study found that higher baseline NIHSS scores and sICH were independently associated with long-term unfavorable outcome. However, the age at onset time, time from onset to groin recanalization, post-treatment TICI scores, or ASPECTS are not independently associated with long-term unfavorable outcome, which is a contrast to the previous studies [19]. These discrepancies may be attributed to the difference of study population, stroke severity and incidence of sICH. In addition, the small sample size and the wide range

87.1%

AIS: acute ischemic stroke; ET: endovascular thrombectomy; SD: standard deviation; IQR, interquartile range; NIHSS: National Institutes of Health Stroke Scale; ASPECTS: Alberta Stroke Program Early CT score; NA: not available; sICH: symptomatic intracerebral hemorrhage; TICI: Thrombolysis in Cerebral Infarction. ⁎ MR CLEAN reports acute cervical carotid stenting in 30 patients (13%) in the intervention group.

of time from onset to groin recanalization may also have some influences on our findings. In the two recently published articles, REVASCAT and MR CLEAN reported their 1-year and 2-year outcome respectively [4,5]. An overview of baseline characteristics, mortality, functional outcome and recurrent stroke after AIS are summarized in Table 5. Compared with 81


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Conflict of interest

REVASCAT and MR CLEAN, the functional independence rate is much higher in this study. This discrepancy may be explained by the high proportion of subjects due to LAA, achieving TICI scores 2b/3 after ET and the slightly younger age of subjects in this study. The proportion of recurrent stroke, sICH, and treatment with additional intra-arterial thrombolysis, permanent intracranial stenting and tirofiban are all much higher in this study. Much of these discrepancies may be attributed to mostly stroke (55%) in this study were due to LAA rather than cardioembolism. Intracranial artery atherosclerosis is more common in Chinese stroke patients [8], and it's hard to achieve artery recanalization using stent retriever device alone in this part of patients [20]. Therefore, a high proportion of subjects in this study was treated with rescue strategies including permanent intracranial stenting and intraarterial thrombolysis, which could achieve sufficient recanalization [21,22]. And additional tirofiban, a GPIIb/IIIa antagonist with a short half-life, was often used to prevent local platelet aggregation and artery re-occlusion. Unfortunately, the use of tirofiban may further increase the risk of intracerebral hemorrhage and caused adverse effects on prognosis [23]. However, the 3-month outcomes of AIS subjects due to LAA and cardioembolism had no significant difference in this study. Therefore, much larger studies are needed to determine the differences in operation techniques and prognosis between the two groups of patients. Although lower than the ACTUAL study, which found that the rate of sICH was 16% [24], rate of sICH (10%) in our study was higher than previously published large randomized trials [3,25–29]. This discrepancy may be attributable to several factors. First, many patients were treated with intraarterial thrombolysis and tirofiban, which may increase the possibility of sICH. In addition, this study is representative of real-world practice, for example, the time from onset to groin puncture and recanalization were much longer than that of previous randomized trials, and several patients with lower ASPECTS (< 6 points) were also included, all these factors may also increase the possibility of sICH. Furthermore, the difference in clinicodemographic characteristics between our study and previous randomized trials may be another contributing factor. Our study has several limitations. First, the number of subjects in our registry is still small and it may have influences on the study results. Therefore, findings of this single-academic center study should be interpreted cautiously. Second, although we had attempted to have all survived subjects come back for clinical visits, in reality, not all of them return for visits. Certain bias cannot be avoided by assessment by telephone interview rather than in-person clinical visits. Third, this is an observational study, and the outcome assessment was not blinded for the baseline characteristics and treatment, potential confounder (including both known and unknown) could have influences on the study results.

The authors declare no financial or other conflicts of interests. References [1] G. Tsivgoulis, A. Safouris, A.H. Katsanos, A.S. Arthur, A.V. Alexandrov, Mechanical thrombectomy for emergent large vessel occlusion: a critical appraisal of recent randomized controlled clinical trials, Brain Behav. 6 (2) (2016) e00418. [2] B.C. Campbell, M.D. Hill, M. Rubiera, B.K. Menon, A. Demchuk, G.A. Donnan, D. Roy, J. Thornton, L. Dorado, A. Bonafe, E.I. Levy, H.C. Diener, M. HernandezPerez, V.M. Pereira, J. Blasco, H. Quesada, J. Rempel, R. Jahan, S.M. Davis, B.C. Stouch, P.J. Mitchell, T.G. Jovin, J.L. Saver, M. Goyal, Safety and efficacy of solitaire stent thrombectomy: individual patient data meta-analysis of randomized trials, Stroke 47 (3) (2016) 798–806. [3] M. Goyal, B.K. Menon, W.H. van Zwam, D.W. Dippel, P.J. Mitchell, A.M. Demchuk, A. Dävalos, C.B. Majoie, d.L.A Van, M.A. de Miquel, Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials, Lancet 387 (10029) (2016) 1723–1731. [4] L.A. van den Berg, M.G.W. Dijkgraaf, O.A. Berkhemer, P.S.S. Fransen, D. Beumer, H.F. Lingsma, C.B.L.M. Majoie, D.W.J. Dippel, A. van der Lugt, R.J. van Oostenbrugge, W.H. van Zwam, Y.B.W.E.M. Roos, Two-year outcome after endovascular treatment for acute ischemic stroke, N. Engl. J. Med. 376 (14) (2017) 1341–1349. [5] A. Davalos, E. Cobo, C.A. Molina, A. Chamorro, M.A. de Miquel, L.S. Roman, J. Serena, E. Lopez-Cancio, M. Ribo, M. Millan, X. Urra, P. Cardona, A. Tomasello, C. Castano, J. Blasco, L. Aja, M. Rubiera, M. Gomis, A. Renu, B. Lara, J. MartiFabregas, B. Jankowitz, N. Cerda, T.G. Jovin, Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised openlabel trial, Lancet Neurol. 16 (5) (2017) 369–376. [6] M.M. Mehndiratta, M. Khan, P. Mehndiratta, M. Wasay, Stroke in Asia: geographical variations and temporal trends, J. Neurol. Neurosurg. Psychiatry 85 (12) (2014) 1308–1312. [7] W. Zhao, R. Che, S. Shang, C. Wu, C. Li, L. Wu, J. Chen, J. Duan, H. Song, H. Zhang, F. Ling, Y. Wang, D. Liebeskind, W. Feng, X. Ji, Low-dose Tirofiban improves functional outcome in acute ischemic stroke patients treated with endovascular Thrombectomy, Stroke 48 (12) (2017) 3289–3294. [8] Y. Wang, X. Zhao, L. Liu, Y.O. Soo, Y. Pu, Y. Pan, Y. Wang, X. Zou, T.W. Leung, Y. Cai, Q. Bai, Y. Wu, C. Wang, X. Pan, B. Luo, K.S. Wong, Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese intracranial atherosclerosis (CICAS) study, Stroke 45 (3) (2014) 663–669. [9] W. Zi, H. Wang, D. Yang, Y. Hao, M. Zhang, Y. Geng, M. Lin, Y. Wan, Z. Shi, Z. Zhou, W. Wang, H. Xu, X. Tian, P. Lv, S. Wang, W. Liu, Z. Wang, X. Liu, F. Guo, D. Zheng, H. Li, M. Tu, P. Jin, G. Xiao, Y. Liu, G. Xu, Y. Xiong, X. Liu, Clinical effectiveness and safety outcomes of endovascular treatment for acute anterior circulation ischemic stroke in China, Cerebrovasc. Dis. 44 (5–6) (2017) 248–258. [10] W.J. Powers, C.P. Derdeyn, J. Biller, C.S. Coffey, B.L. Hoh, E.C. Jauch, K.C. Johnston, S.C. Johnston, A.A. Khalessi, C.S. Kidwell, J.F. Meschia, B. Ovbiagele, D.R. Yavagal, C. American Heart Association Stroke, American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association, Stroke 46 (10) (2015) 3020–3035. [11] E.C. Jauch, J.L. Saver, H.P. Adams Jr., A. Bruno, J.J. Connors, B.M. Demaerschalk, P. Khatri, P.W. McMullan Jr., A.I. Qureshi, K. Rosenfield, P.A. Scott, D.R. Summers, D.Z. Wang, M. Wintermark, H. Yonas, C. American Heart, Association Stroke, N, Council on Cardiovascular, D. Council on Peripheral Vascular, C. Council on Clinical, Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association, Stroke 44 (3) (2013) 870–947. [12] H.P. Adams Jr., G. del Zoppo, M.J. Alberts, D.L. Bhatt, L. Brass, A. Furlan, R.L. Grubb, R.T. Higashida, E.C. Jauch, C. Kidwell, P.D. Lyden, L.B. Morgenstern, A.I. Qureshi, R.H. Rosenwasser, P.A. Scott, E.F. Wijdicks, Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the atherosclerotic peripheral vascular disease and quality of care outcomes in research interdisciplinary working groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists, Stroke 38 (5) (2007) 1655–1711. [13] S. Jung, M.L. Mono, U. Fischer, A. Galimanis, O. Findling, G.M. De Marchis, A. Weck, K. Nedeltchev, G. Colucci, P. Mordasini, C. Brekenfeld, M. El-Koussy, J. Gralla, G. Schroth, H.P. Mattle, M. Arnold, Three-month and long-term outcomes and their predictors in acute basilar artery occlusion treated with intra-arterial thrombolysis, Stroke 42 (7) (2011) 1946–1951. [14] H. Gensicke, D.J. Seiffge, A.E. Polasek, N. Peters, L.H. Bonati, P.A. Lyrer, S.T. Engelter, Long-term outcome in stroke patients treated with IV thrombolysis, Neurology 80 (10) (2013) 919–925. [15] H.S. Jorgensen, H. Nakayama, H.O. Raaschou, T.S. Olsen, Stroke. Neurologic and functional recovery the Copenhagen stroke study, Phys. Med. Rehabil. Clin. N. Am. 10 (4) (1999) 887–906. [16] H.S. Jorgensen, H. Nakayama, H.O. Raaschou, J. Vive-Larsen, M. Stoier, T.S. Olsen, Outcome and time course of recovery in stroke. Part II: time course of recovery. The

5. Conclusions In conclusion, long-term outcome of recent RCTs can be generalized to the real-world clinical practice in our stroke center, and over half of AIS patients can achieve long-term favorable outcomes after ET. Higher baseline NIHSS scores and sICH are independently associated with longterm unfavorable outcome. Further studies are needed to investigate the discrepancy of operation techniques and outcomes between AIS patients with LAA and those with cardioembolism. Funding This work was supported by The National Key R&D Program of China (2016YFC1301502), Chang Jiang Scholars Program (No. T2014251), The National Natural Science Foundation of China (No. 81701287), and The Capital Health Research and Development of Special (2016-4-1032), China Postdoctoral Science Foundation, and Beijing Postdoctoral Research Foundation. 82


W. Zhao et al.

Copenhagen stroke study, Arch. Phys. Med. Rehabil. 76 (5) (1995) 406–412. [17] T.T. Sajobi, B.K. Menon, M. Wang, O. Lawal, A. Shuaib, D. Williams, A.Y. Poppe, T.G. Jovin, L.K. Casaubon, T. Devlin, D. Dowlatshahi, C. Fanale, M.W. Lowerison, A.M. Demchuk, M. Goyal, M.D. Hill, Early trajectory of stroke severity predicts long-term functional outcomes in ischemic stroke subjects: results from the ESCAPE trial (endovascular treatment for small Core and anterior circulation proximal occlusion with emphasis on minimizing CT to recanalization times), Stroke 48 (1) (2017) 105–110. [18] U. Fischer, M.L. Mono, M. Zwahlen, K. Nedeltchev, M. Arnold, A. Galimanis, S. Bucher, O. Findling, N. Meier, C. Brekenfeld, J. Gralla, R. Heller, B. Tschannen, H. Schaad, G. Waldegg, T. Zehnder, A. Ronsdorf, P. Oswald, G. Brunner, G. Schroth, H.P. Mattle, Impact of thrombolysis on stroke outcome at 12 months in a population: the Bern stroke project, Stroke 43 (4) (2012) 1039–1045. [19] F. Sarzetto, S. Gupta, N.M. Alotaibi, P. Howard, L. da Costa, C. Heyn, P.J. Maralani, D. Guha, R.H. Swartz, K. Boyle, V.X. Yang, Outcome evaluation of acute ischemic stroke patients treated with endovascular Thrombectomy: a single-institution experience in the era of randomized controlled trials, World Neurosurg. 99 (2017) 593–598. [20] J.S. Lee, J.M. Hong, K.S. Lee, H.I. Suh, J.W. Choi, S.Y. Kim, Primary stent retrieval for acute intracranial large artery occlusion due to atherosclerotic disease, J. Stroke 18 (1) (2016) 96–101. [21] C. Brekenfeld, G. Schroth, H.P. Mattle, D.D. Do, L. Remonda, P. Mordasini, M. Arnold, K. Nedeltchev, N. Meier, J. Gralla, Stent placement in acute cerebral artery occlusion: use of a self-expandable intracranial stent for acute stroke treatment, Stroke 40 (3) (2009) 847–852. [22] C. Roth, P. Papanagiotou, S. Behnke, S. Walter, A. Haass, C. Becker, K. Fassbender, M. Politi, H. Korner, M.S. Romann, W. Reith, Stent-assisted mechanical

[23]

[24]

[25]

[26]

[27]

[28]

[29]

83

recanalization for treatment of acute intracerebral artery occlusions, Stroke 41 (11) (2010) 2559–2567. L. Kellert, C. Hametner, S. Rohde, M. Bendszus, W. Hacke, P. Ringleb, S. Stampfl, Endovascular stroke therapy: tirofiban is associated with risk of fatal intracerebral hemorrhage and poor outcome, Stroke 44 (5) (2013) 1453–1455. Y. Hao, D. Yang, H. Wang, W. Zi, M. Zhang, Y. Geng, Z. Zhou, W. Wang, H. Xu, X. Tian, P. Lv, Y. Liu, Y. Xiong, X. Liu, G. Xu, Predictors for symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke, Stroke 48 (5) (2017) 1203–1209. O.A. Berkhemer, P.S. Fransen, D. Beumer, V.D.B. La, H.F. Lingsma, A.J. Yoo, W.J. Schonewille, J.A. Vos, P.J. Nederkoorn, M.J. Wermer, A randomized trial of intraarterial treatment for acute ischemic stroke, N. Engl. J. Med. 372 (1) (2015) 11–20. B.C. Campbell, P.J. Mitchell, T.J. Kleinig, H.M. Dewey, L. Churilov, N. Yassi, B. Yan, R.J. Dowling, M.W. Parsons, T.J. Oxley, Endovascular therapy for ischemic stroke with perfusion-imaging selection, N. Engl. J. Med. 372 (11) (2015) 1009–1018. M. Goyal, A.M. Demchuk, B.K. Menon, M. Eesa, J.L. Rempel, J. Thornton, D. Roy, T.G. Jovin, R.A. Willinsky, B.L. Sapkota, Randomized assessment of rapid endovascular treatment of ischemic stroke, N. Engl. J. Med. 372 (11) (2015) 1019–1030. T.G. Jovin, A. Chamorro, E. Cobo, M.A. de Miquel, C.A. Molina, A. Rovira, R.N.L. San, J. Serena, S. Abilleira, M. Rib, Thrombectomy within 8 hours after symptom onset in ischemic stroke, N. Engl. J. Med. 372 (24) (2015) 2296–2306. J.L. Saver, M. Goyal, A. Bonafe, H.C. Diener, E.I. Levy, V.M. Pereira, G.W. Albers, C. Cognard, D.J. Cohen, W. Hacke, Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke, N. Engl. J. Med. 372 (24) (2015) 2285–2295.