Comparison of Outcomes After Mechanical Thrombectomy Alone or Combined with Intravenous Thrombolysis and Mechanical Thrombectomy for Patients with Acute Ischemic Stroke due to Large Vessel Occlusion

Comparison of Outcomes After Mechanical Thrombectomy Alone or Combined with Intravenous Thrombolysis and Mechanical Thrombectomy for Patients with Acute Ischemic Stroke due to Large Vessel Occlusion

Accepted Manuscript Comparison of Outcome After Mechanical Thrombectomy Alone or Combined Intravenous Thrombolysis and Mechanical Thrombectomy for Pat...

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Accepted Manuscript Comparison of Outcome After Mechanical Thrombectomy Alone or Combined Intravenous Thrombolysis and Mechanical Thrombectomy for Patients with Acute Ischemic Stroke due to Large Vessel Occlusion Jai Ho Choi, M.D, Sang Hyuk Im, M.D, Ki Jeong Lee, M.D, Ja Seong Koo, M.D, PhD, Bum Soo Kim, M.D, PhD, Yong Sam Shin, M.D, PhD PII:

S1878-8750(18)30399-1

DOI:

10.1016/j.wneu.2018.02.126

Reference:

WNEU 7541

To appear in:

World Neurosurgery

Received Date: 5 December 2017 Revised Date:

20 February 2018

Accepted Date: 22 February 2018

Please cite this article as: Choi JH, Im SH, Lee KJ, Koo JS, Kim BS, Shin YS, Comparison of Outcome After Mechanical Thrombectomy Alone or Combined Intravenous Thrombolysis and Mechanical Thrombectomy for Patients with Acute Ischemic Stroke due to Large Vessel Occlusion, World Neurosurgery (2018), doi: 10.1016/j.wneu.2018.02.126. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Comparison of Outcome After Mechanical Thrombectomy Alone or Combined Intravenous Thrombolysis and Mechanical Thrombectomy for Patients with Acute Ischemic Stroke due to Large Vessel Occlusion

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Jai Ho Choi M.D1, Sang Hyuk Im M.D3, Ki Jeong Lee M.D2, Ja Seong Koo M.D, PhD2, Bum Soo Kim M.D, PhD3, Yong Sam Shin M.D, PhD1

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From the Department of Neurosurgery1, Department of Neurology2 and Department of Radiology3, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Banpo-daero 222, Seocho-gu, Seoul

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137-701, Republic of Korea

To whom correspondence should be addressed: Yong Sam Shin

Key words

Stroke

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Thrombectomy

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Endovascular treatment

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(E-mail : [email protected])

Thrombolysis

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Short title: Thrombectomy alone vs combined thrombolysis and thrombectomy for acute ischemic stroke 1

ACCEPTED MANUSCRIPT BACKGROUND: Whether intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) provides additional benefits remains controversial. We aimed to compare clinical and radiologic outcomes between IVT+MT and MT alone groups. METHODS: The clinical and radiological features of anterior circulation stroke patients due to large vessel

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occlusion (LVO) treated with MT within 8 hours from symptom onset were retrospectively reviewed from the prospectively collected database. We compared successful reperfusion, functional independence and mortality rate at 90 days, and symptomatic intracranial hemorrhage (sICH) as clinical endpoints between the two groups. RESULTS: Of 81 patients included in this study, 38 (46.9%) received MT alone (mean age±SD, 72.6±14.1

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years; 17 males, 44.7%), and 43 (mean age±SD, 68.9±12.8 years; 29 males, 67.4%) received IVT+MT. There were no significant differences in patient baseline characteristics between the two groups except male

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predominance in combined group. The onset to groin puncture time (221.6±110.5 vs. 204.7±63.7 min, p=0.472) and successful reperfusion rate (Thrombolysis in Cerebral Infarction 2b/3, 60.5% vs. 58.1%, p=0.827) did not differ significantly. The rate of favorable functional outcome (modified Rankin score 0-2, 36.8% vs. 51.2%, p=0.263) and mortality (18.4% vs. 9.3%, p=0.332) at 90 days, and sICH (5.3% vs. 4.6%, p=1.000) were also not significantly different between the two groups.

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CONCLUSIONS: This study suggests that prior IVT may not facilitate successful reperfusion and favorable functional outcome in patients with anterior circulation stroke treated with MT. MT alone can be a safe and

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effective treatment modality in patients who are ineligible for IVT due to various reasons.

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ACCEPTED MANUSCRIPT INTRODUCTION Intravenous thrombolysis (IVT) with tissue plasminogen activator (tPA) has been the gold standard treatment for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset for several years.1 However, this therapeutic modality showed low efficacy in AIS patients with large vessel occlusion (LVO). Low recanalization

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rates of about 35% in middle cerebral artery (MCA) occlusions and about 6% in a carotid-T occlusions have been reported.2 Five recent randomized controlled trials (RCTs) provided clear evidence that mechanical thrombectomy (MT) with stent retrievers was superior to IVT alone in AIS with LVO.3-7 Thus, current guidelines recommend sequential MT with IVT within 4.5 hours among the patients with anterior circulation

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stroke caused by LVO.8,9 Accordingly, tPA should be administrated in patients who are eligible for IVT without delay despite the consideration of MT.10 However, although only small number of patients received MT alone,

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the aforementioned RCTs found no significant difference in its therapeutic effects between patients with or without prior IVT in a subgroup analysis.3-7 A recent pooled analysis of the SWIFT and STAR studies published by Coutinho JM et al. also showed that IVT before MT did not appear to provide a clinical benefit over MT alone.11 In contrast, some authors suggested that prior IVT facilitates successful recanalization and improves clinical outcomes of AIS with LVO.12,13 Whether the prior IVT provides additional benefits is not yet well

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established and conflicting results still exists. Moreover, a considerable number of patients with AIS caused by LVO are ineligible for IVT due to absolute and relative contraindications for IVT. MT alone can be one of possible treatment option for these patients.

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The purpose of this study was to compare the clinical and radiological outcomes of IVT prior to MT (IVT+MT) and MT alone groups and investigate whether IVT prior to MT provides additional benefits for

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reperfusion and functional outcomes compared to MT alone

METHODS

Study Population

Between January 2009 and June 2017, all consective AIS patients treated with MT with or without IVT in a single tertiary institute were prospectively collected using a standardized case report form including clinical information, radiological findings, and outcomes. Patients were considered eligible if the following inclusion 3

ACCEPTED MANUSCRIPT criteria were fulfilled: 1) acute ischemic stroke due to occlusion of anterior circulation large artery, 2) endovascular recanalization using mechanical thrombectomy within 8 hours after symptom onset, or 3) mechanical thrombectomy using a stent retriever and/or suction device. Of 141 consecutive AIS patients, we excluded those who received MT with thrombectomy devices except a stent retriever or suction device (n=30)

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and had a posterior circulation infarction involving vertebrobasilar and posterior cerebral artery (n=16). We also excluded wake-up stroke patients who visited our hospital after ≥8 hours since the last normal condition (n=14). After exclusion, a total of 81 AIS patients were ultimately included in this study.

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Clinical and Radiologic Evaluations

All patients underwent computed tomogram angiography (CTA) with or without CT perfusion for

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preoprocedural evaluation. Baseline patient demographics, stroke risk factors, onset time, and symptoms including National Institutes of Health Stroke Scale (NIHSS) score were also checked in the emergency room (ER). The use of prior IVT before MT in patients with relative contraindications to IVT, such as advanced age and recent myocardial infarction14 was decided at the

treating neurologist’s discretion based on radiological

findings, initial symptoms, and symptom onset time. The MT was performed by one interventional

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neuroradiologist (BS Kim) and two interventional neurosurgeons (YS Shin, JH Choi) according to the consensus of the treating neurologist and neurointerventionist.

Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction (TICI) 2b to 3 score on the final

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angiography after MT. The presence of postprocedural intracranial hemorrhage (ICH) was evaluated by CT or gradient echo imaging (GRE) within 24 hours. Symptomatic ICH was defined as any hemorrhage within 24 hours related to an increase of 4 points or more on the NIHSS score or that caused death.1,11 Clinical outcome

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was assessed by the modified Rankin Scale (mRS) at 90 days of follow-up. Good functional outcome was defined as mRS score of 2 or less.

Statistical Analysis

We performed a statistical analysis using SPSS version 17 (SPSS, Chicago, Illinois, USA). Categorical variables were analyzed by the chi-square test or Fisher’s exact test to compare the IVT+MT and MT alone groups. Continuous variables were compared using a t-test or the Mann-Whitney U test. A univariate analysis to 4

ACCEPTED MANUSCRIPT evaluate the relevant factors for good functional outcome was performed using Fisher’s exact test, the chisquare test, a t-test, or the Mann-Whitney U test, as appropriate. A multivariate logistic regression analysis to determine risk factors for good functional outcome was performed including variables with p value < 0.20 in

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univariate analysis. Less than 0.05 of p value was regarded as statistically significant.

RESULTS

Baseline Patient Characteristics

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Of the 81 patients included in this study, 38 received MT alone and 43 received IVT prior to MT for AIS caused by LVO. The most common cause of receiving MT alone was an advanced age over 80 years old (n=11),

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followed by >4.5 hours between known stroke onset and effective therapy (n=9), recent major surgery (n=7), coagulopathy (INR>1.7, thrombocytopenia, or new oral anticoagulant, n=6), recent stroke or myocardial infarction (n=3), and others (n=2). Baseline patient characteristics are summarized in Table 1. The proportion of males was higher in the IVT+MT group than the MT alone group (67.4% vs. 44.7%, p=0.040). Other clinical characteristics including age, baseline NIHSS, medical history, and stroke etiology did not differ significantly

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between the two groups. Angiographically, occlusion location did not differ significantly between the two groups. The majority of thrombectomy devices was stent retriever in both groups (76.3% in the MT alone group

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vs. 81.4% in the IVT+MT group, p=0.402).

Comparison of Radiological and Functional Outcome between the MT alone and IVT+MT Groups. Table 2 shows the details of the procedural, clinical, and safety outcomes of the MT alone group and IVT+MT

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group. The time interval between symptom onset to groin puncture time of the MT and IVT+MT groups was 221.6±110.5 and 204.7±63.7 min, respectively, and there was no significant difference between the two groups (p=0.412). The TICI 2b or 3 reperfusion rate at the end of the procedure of the MT alone group (n=23, 60.5%) and IVT+MT group (n=22, 58.1%) did not differ significantly (p=0.827). The rate of TICI 3 reperfusion was also not significantly different between the two groups (26.3% in the MT alone group vs. 32.6% in the IVT+MT group, p=0.539). The rate of good functional outcome (mRS 0-2) (36.8% in the MT alone group vs. 58.1% in the IVT+MT group, p=0.263) and mortality (18.4% in the MT alone group vs. 9.3% in the IVT+MT group, 5

ACCEPTED MANUSCRIPT p=0.332) at 3 months was also not significnatly different between the two groups. The occurrence of symptomatic ICH after MT did not differ significantly (5.3% in the MT alone group vs. 4.6% in the IVT+MT group, p=1.000). Groin complications occurred in 11 patients. The most common groin complication was blood oozing at the punture site (severn patients), and followed by groin hematoma (two patients) and puncture site

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pain (two patients). Blood oozing and groin hematoma were managed by manual compression. There were no serious complications such as pseudoaneurysm, dissection, or retroperitoneal hematoma. The occurrence rate of groin complication did not differ between the MT alone group (5 of 38 patients, 13.2%) and the IVT+MT group (6 of 43 patients, 14%) (p=0.917).

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We performed a postprocedural magnetic resonance image (MRI) within 48 hours in 72 of 81 patients. Postprocedural diffusion weighted image (DWI) were analyzed with the help of in-house program developed for

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MATLAB (MathWorks, Natick, Massachusetts, USA) and adjusted manually to measure postprocedural infarction volume. We defined infarction core with an apparent diffusion coefficient (ADC) value of <600mm2/s on ADC maps and excluded regions with a cluster volume ≤1mL among the selected regions with an ADC value of <600mm2/s. The mean infarction volume was not different between the MT alone group (71.3±106.8ml) and the IVT+MT group (55.9±92.7ml, p=0.445). We performed postprocedural magnetic resonance angiography

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(MRA) within 7 days in cases with a non- or partially recanalized LVO (TICI 0 to 2a) to evaluate delayed recanalization according to IVT use. Follow-up MRA was available in 4 of 15 (26.7%) patients treated with MT alone and in 10 of 18 (55.5%, p=0.095) patients treated with IVT+MT. The delayed recanalization (visualization

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of distal flow) on MRA occurred in 3 of 4 patients (75%) treated with MT alone and in 4 of 10 patients (40%) treated with IVT+MT. There was no significant difference in delayed recanalization by IVT use (p=0.237). The rate of good functional outcome at 3 months was also not differnet between the MT alone group (1 of 15

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patients, 6.6%) and the IVT+MT group (3 of 18 patients, 16.7%) (p=0.607).

Uni- and Multivariate Analyses of Associated Factors with Good Functional Outcomes at 3 Months The results of uni- and multivariate analysis of associated factors with a good functional outcome (mRS 0-2) at 3 months are summarized in Table 3. A low baseline NIHSS, absence of hypertension and diabetes mellitus (DM), and successful reperfusion (TICI 2b or more) were related to good functional outcomes on univariate analysis. Other clinical and radiological characteristics showed no significant difference between the two groups. 6

ACCEPTED MANUSCRIPT A multivariate logistic regression analysis was performed with variables that were significantly associated with good functional outcomes (p<0.05) and had marginal results (p<0.2) on univariate analysis. The multivariate analysis results showed that the following factors were significantly associated with a good functional outcome (p<0.05): baseline NIHSS (odds ratio(OR) 1.215, 95% Confidence interval(CI) 1.151-6.818), onset to groin

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puncture time (OR 1.011, 95% CI 1.002-1.020), and successful reperfusion (OR 0.044, 95% CI 0.009-0.212).

DISCUSSION

The three RCTs published in 2013 have contributed to uncertainty regarding the efficacy of the endovascular

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treatment after IVT with tPA.15-17 However, various questions have been raised regarding the design and conduct of these RCTs, including a relatively long interval before endovascular treatment, the absence of pretreatment

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vascular imaging to confirm LVO, and the limited use of third generation MT devices such as a stent retriever or suction device. Five recent RCTs were designed to complement these weak points of previous studies.

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Therefore, we included 81 AIS patients with anterior circulation LVO who were treated with a stent retriever and/or suction device within 8 hours after symptom onset to make the study population similar to those of the recent five RCTs. Thirty patients treated with methods other than a stent retriever and/or suction device were

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excluded from this study. The details of these methods were as follows: 1) three with microwire and microcatheter to-and-pro technique, 2) four with balloon and intraarterial urokinase (IAUK) injection, 3) five with microwire and microcatheter to-and-pro technique and IAUK, 4) six with microwire and microcatheter to-

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and-pro technique and balloon, 5) five with balloon, 6) three with microwire and microcatheter to-and-pro technique and IA tirofiban, and 7) four with balloon and permanent stenting. Because these treatment modalities are too heterogenous, we suspected that the results containing these data may not be powerful enough to enable

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us to draw meaningful conclusions, and thus we excluded these patients. Before the recent five RCTs showed that MT with a stent retriever combined with IVT is superior to IVT alone in AIS patients due to LVO in anterior circulation3-7, IVT with tPA was the only reperfusion therapy with a proven benefit on clinical outcome in AIS patients within 4.5 hours of symptom onset.18 Although IVT alone showed low effectiveness in AIS caused by LVO because of low recanalization rate2,19, preceding IVT have been thought to have a positive influence on the clinical outcome after MT.

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ACCEPTED MANUSCRIPT First, IVT could reduce the procedural time and facilitate the successful reperfusion with MT by reducing the number of passes with a stent retriever and decreasing the frequency of microvasular thrombosis, because IVT could enhance the fibrinolytic process.20-22 In our study, there was no significant difference in the rate of successful reperfusion and good functional outcome at 3 months between the IVT+MT group and the MT alone

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group. Moreover, the number of passes with the stent retriever did not differ between the two groups. Similar to our data, a recent published pooled analysis of the SWIFT and STAR studies by Coutinho JM et al. and comparison data between IVT+MT and MT alone by Weber R et al. also showed that the number of passes with a stent, functional outcome, and successful reperfusion rate was not significantly different between the two

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groups.11,23 In addition, in a recently published meta-analysis of individual patient data from five RCTs by Goyal M et al., no differences were found in clinical outcomes between IVT+MT and MT alone.24

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Second, successful recanalization is not always achieved with MT, and such patients may benefit from IVT. Kablau et al. reported that patients receiving IVT with persistent MCA occlusion showed early improvement in mRS and NIHSS compared with patients not receiving IVT.25 Also, IVT could affect the delayed reperfusion of the occluded vessel over time . In the ESCAPE trial, IVT often leads to delayed reperfusion of the occluded vessel.5 Follow-up CTA was obtained after a median time of 7 hours after symptom onest in the control group.

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Among those treated with IVT, delayed recanalization was observed in approximately 33% of patients compared with 7% of patients not treated with IVT. However, the clinical benefit of this delayed reperfusion is unclear. In our study, there was no difference in the delayed recanalization of the persistent occluded vessel regardless of

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IVT use on follow-up MRA within 7 days after symptom onset and functional outcome at 3 months measured by mRS was also not different between the IVT+MT and MT alone groups. Finally, one of the main reason to use preceding IVT is that IVT may result in early recanalization, which

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make following MT unnecessary. However, the five recent RCTs suggested that such early recanalization, which negatesthe need for MT, occurred in only less than 7% of all patients receiving IVT.3-7 These data could ensure that the chance of early recanalization in response to IVT depends on the occlusion location , with distal internal carotid artery (ICA) and T occlusion showing a poor response to IVT as seen in previous studies.2,19 On the other hand, the IVT use may have some disadvantages for patients with LVO. IVT may increase the risk of hemorrhagic complications.18,26 In addition, the fragmentation of the thrombus after IVT use might potentially reduce the efficacy of MT for complete reperfusion of the distal vessels.11 IVT before MT could be a 8

ACCEPTED MANUSCRIPT cause of delayed groin puncture for MT, especially if AIS patients with LVO receive IVT at a local stroke centers where MT is not available and who must be transferred to a comprehensive stroke center.10 Finally, IVT with tPA is a costly therapy. Whether IVT prior to MT facilitates successful reperfusion and good functional outcome remains

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controversial because a direct comparison between IVT+MT and MT alone has not yet been studied in a RCT. Only a few studies previously compared the clinical and radiological outcomes in patients with LVO needing MT according to the prior use of IVT.10-13,20,22,23,27-33 The details of these previous studeis are summarized in Table 4. Some authors have suggested that preceding IVT may facilitate successful reperfusion and good

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functional outcome compared to MT alone.12,13,20,22,27,31,32 However, each of these reports had shortcomings, with different study populations compared to the five recent RCTs, or inhomogeneous endovascular treatment

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methods, or a lack of multivariate regression analysis to identify an independent predictor of good functional outcome. More recently, especially after the publication of thesefive RCTs in 2015, studies asserting that the outcomes after combined IVT+MT or MT alone are not different have increased in number.10,11,23,28-30,33 Similar to these reports, our results show that preceding IVT might not have additional benefits in terms of clinical and radiological outcomes in anterior circulation stroke patients caused by LVO treated with MT using a stent

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retriever or suction device within 8 hours from symptom onset. In addition, independent predictors for good functional outcome included a lower baseline NIHSS, faster onset to groin puncture time, and successful reperfusion (TICI 2b-3) on multivariate logistic regression analysis. The use of IVT was not an independent

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predictor of a good functional outcome in AIS patients treated with MT in our study , as in a previous report.23 There were some limitations to this study. First, the sample size was small, and thus the results may not be enousgh to draw definite conclusions about the differences between IVT+MT and MT alone. Second, because of

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inclusion of consecutive patients without randomization, selection bias and a wide CI could exist inherently. Further prospective large population RCT should be investigated to conclude whether prior IVT has additional benefits and exclude any limitations.

CONCLUSIONS

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ACCEPTED MANUSCRIPT This study suggests that prior IVT may not facilitate successful reperfusion or a favorable functional outcome in patients with anterior circulation stroke treated with MT. MT alone can be a safe and effective treatment modality in patients who are ineligible for IVT due to various reasons. ACKNOWLEDGEMENTS

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The authors thank Yoonho Nam and Na-Young Shin for their help measuring postprocedural infarction volume

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on an ADC map

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intravenous thrombolysis facilitates endovascular mechanical recanalization in large intracranial artery occlusion. Int J Stroke. 2012;7:14-18.

Tsivgoulis G, Katsanos AH, Mavridis D, Magoufis G, Arthur A, Alexandrov AV. Mechanical Thrombectomy Improves Functional Outcomes Independent of Pretreatment With Intravenous

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Thrombolysis. Stroke. 2016;47:1661-1664.

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ACCEPTED MANUSCRIPT Table 1. Comparison of patient baseline characteristics in the MT alone and IVT+MT groups Variables

MT alone group

IVT+MT group

(n=38)

(n=43)

p value

17 (44.7%)

29 (67.4%)

0.040

Age (years, mean±SD)

72.6±14.1

68.9±12.8

0.217

Baseline NIHSS

15 (11-17)

13 (10-16)

Atrial fibrillation

25 (65.8%)

22 (51.2%)

Hypertension

25 (65.8%)

29 (67.4%)

0.875

Diabetes mellitus

12 (31.6%)

7 (16.3%)

0.105

Hyperlipidemia

22 (57.9%)

Previous stroke

8 (21.1%)

Oral anticoagulants

8 (21.1%)

Antiplatelet agents

15 (39.5%)

Smoking

12 (31.6%)

(median, Q25-Q75)

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0.249

3 (7.0%)

0.065

19 (44.2%)

0.668

18 (41.9%)

0.339 0.229

3 (7.9%)

9 (20.9%) 8 (18.6%)

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Occlusion location

5 (11.6%)

26 (60.5%)

Atherothrombotic

10 (26.3%)

0.284

17 (44.7%)

21 (48.8%)

5 (13.2%)

9 (20.9%)

9 (23.7%)

8 (18.6%)

0 (0%)

1 (2.3%)

Tandem (ICA and M1)

7 (18.4%)

4 (9.3%)

Right side

18 (47.4%)

24 (55.8%)

M1 M2 ICA A1

0.183

0.375

25 (65.8%)

Cardioembolic

0.451

29 (67.4%)

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Etiology

Others

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Medical history

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Male

0.448 0.402

Thrombectomy devices 1

ACCEPTED MANUSCRIPT Stent retriever

26 (68.4%)

34 (79.1%)

Suction device

9 (23.7%)

8 (18.6%)

Combined

3 (7.9%)

1 (2.3%)

MT, mechanical thrombectomy; IVT, intravenous thrombolysis; SD, standard deviation; ICA, internal carotid

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artery.

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ACCEPTED MANUSCRIPT Table 2. Comparison of procedural, clinical, and safety outcomes in the MT alone and IVT+MT groups Variables

p value

MT alone group

Combined

(n=38)

MT and IVT group (n=43)

70.7±91.4

Onset to door time

83.9±72.8

0.472

128.2±61.0

Onset to IVT time

204.7±63.7

1.9±0.97

1.7±0.97

TICI 2b or 3 reperfusions

23 (60.5%)

25 (58.1%)

TICI 3 reperfusion

10 (26.3%)

No. of passes with stent

Outcome at 90days mRS 0-2

14 (36.8%)

Mortality

7 (18.4%)

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retriever (mean±SD)

22 (51.2%)

0.263

4 (9.3%)

0.332

2 (4.6%)

1.000 0.917

5 (13.2%)

6 (14%)

Hematoma

0

2

Pain

1

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Groin complications

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4

3

71.3±106.8

55.9±92.7

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0.827 0.539

2 (5.3%)

Infarction volume on

0.376

14 (32.6%)

Symptomatic ICH

Blood oozing

0.412

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221.6±110.5

Onset to puncture time

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Time (min, mean±SD)

0.445

ADC map

MT, mechanical thrombectomy; IVT, intravenous thrombolysis; SD, standard deviation; ICA, internal carotid artery; TICI, thrombolysis in cerebral infarction; mRS, modified Rankin score; ICH, intracranial hemorrhage; ADC, apparent diffusion coefficient

3

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Table 3. Uni- and multivariate analysis of association with good functional outcome (mRS 0-2) at 3 months Good outcome

Poor outcome

Univariate

Multivariate

at 3 months (mRS 0-2)

at 3 months (mRS 3-6)

analysis

analysis

(n=35)

(n=46)

(p value)

23 (65.7%)

23 (50%)

0.157

Age (years, mean±SD)

68.7±14.9

72.1±12.2

0.282

Baseline NIHSS

11 (9-14)

15 (12-17)

<0.001

Atrial fibrillation

19 (54.3%)

28 (60.9%)

Hypertension

19 (54.3%)

35 (76.1%)

Diabetes mellitus

3 (8.6%)

Hyperlipidemia

Odds ratio

95% confidence interval

(p value)

0.915

0.205-4.082

0.020

1.215

1.032-1.432

0.039

0.460

1.704

0.415-7.003

16 (34.8%)

0.006

0.399

2.238

0.345-14.523

25 (71.4%)

26 (56.5%)

0.169

0.268

0.460

0.116-1.817

Previous stroke

4 (11.4%)

9 (19.6%)

0.375

Oral anticoagulants

2 (5.7%)

9 (19.6%)

0.071

0.756

1.429

0.150-13.588

Antiplatelet agents

15 (42.9%)

Smoking

12 (34.3%)

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Etiology

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Medical history

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(median, Q25-Q75)

0.907

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Male

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Variables

19 (41.3%)

0.888

18 (39.1%)

0.655 0.834 4

Cardioembolic

22 (62.9%)

29 (63%)

Atherothrombotic

6 (17.1%)

6 (13%)

Others

7 (20%)

11 (23.9%) 0.506

Occlusion location 17 (48.6%)

21 (45.7%)

M2

8 (22.9%)

6 (13%)

ICA

3 (8.6%)

9 (19.6%)

A1

0 (0%)

1 (2.2%)

Tandem (ICA and M1)

4 (11.4%)

7 (15.2%)

Right side

17 (48.6%)

25 (54.3%)

22 (62.9%)

21 (45.7%)

Onset to door time

72.5±68.2

81.7±91.4

0.621

Onset to IVT time

127.6±51.7

128±70.8

0.953

Onset to puncture time

196.1±64.8

225.17±102.1

2b

or

3

32 (91.4%)

reperfusions Symptomatic ICH

0 (0%)

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0.411

0.567

0.146-2.197

0.123

0.013

1.011

1.002-1.020

16 (34.8%)

<0.001

<0.001

0.044

0.009-0.212

4 (8.7%)

0.074

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0.124

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Time (min, mean±SD)

0.606

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M1

TICI

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SD, standard deviation; TPA, tissue plasminogen activator; MT, mechanical thrombectomy; ICA, internal carotid artery; IVT, intravenous thrombolysis; TICI,

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Thrombolysis in Cerebral Infarction; ICH, intracranial hemorrhage.

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Table 4. Results of previous studies comparing outcomes of MT alone or IVT+MT treatment Device

Successful recanalization rate

mRS 0-2 at 3 months

(TICI 2b,3 or TIMI 2,3) IVT

MT

+MT Davalos A et

67

74

IVT

p value

MT

+MT SR

56

64

(81%)

(88%)

MT,

32

74

NOS

(60%)

(71%)

MT,

49

35

NOS

(79.03%)

(83.3%)

SR

22

24

al.

+MT N/S

28

49

(42%)

(66%)

(2012) Bhatia R et

53

104

al.

0.21

23

T et al.

Guedin P et

40

28

(55%)

al. (2015) Leker RR et

33

24

SR

28

0.585

0.011

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(2014)

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42

(85.7%)

21

1.00

p value

<0.01

0.87

(48%)

20/58

15/40

(34.48%)

(37.5%)

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62

46

(43%)

(2014) Kass-Hout

IVT

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sICH

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No of Cases

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Study

21

19

(52.5%)

(67.9%)

17

10 7

0.643

0.21

N/S

MT

IVT

Mortality at 3 months

p value

MT

+MT

3

2

(5%)

(3%)

6

7

(12%)

(7%)

6

5

(9.68%)

(11.9%)

2

2

(5%)

(7.1%)

0

2

IVT

p value

+MT N/S

0.365

0.753

1.00

0.17

16

13

(24%)

(18%)

16

20

(30%)

(21%)

18

8

(29.03%)

(19.04%)

7

3

(17.5%)

(10.7%)

3

3

N/S

0.316

0.561

0.51

N/S

ACCEPTED MANUSCRIPT

al.

(85%)

(87.5%)

35

31

(87.5%)

(77.5%)

81.8%

90.9%

(59%)

(49%)

17

17

(42.5%)

(42.5%)

6

17

(0%)

(8%)

1

1

(2.5%)

(2.5%)

6.1%

9.1%

(10%)

(18%)

8

19

(20%)

(47.5%)

10

6

(30.3%)

(18.2%)

227

263

0.006

(2015) 40

SR, SD

Morvay A et

0.39

al.

Merlino G

33

33

SR, SD

0.4

et al. (2017) 2221

et al.

30

35

(2017)

567

68

0.67

0.01

520

NOS

/1226

/1652

(OR:

/1174

/1769

(OR:

/1143

/1471

/1202

/1774

(OR

(75%)

(79.9%)

1.46)

(44.2%)

(48.6%)

1.27)

(3.9%)

(4.6%)

(18.8%)

(14.8%)

0.71)

23

26

N/D

3/23

11/26

0.03

0/23

0/26

8/23

5/26

0.332

(13%)

(42%)

(0%)

(0%)

(35%)

(19%)

271

267

16

19

106

93

(59.5%)

(59.4%)

(3.5%)

(3.3%)

(23.2%)

(20.7%)

MT,

MT, NOS

455 (76%)

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et al.

599

45

0.2

1320

(2017) Alilleira S

0.02

0.6

0.007

926

NOS

T et al.

861

1.00

MT,

(2017)

Pfefferkorn

(51.5%)

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1332

(18.2%)

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Mistry EA

0.004

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(2016)

1.00

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40

SC

Broeg-

449

(79.2%)

0.166

8

0.302

N/S

0.859

0.613

ACCEPTED MANUSCRIPT

131

160

SR

JM et al.

105/124

127/151

(84.7%)

(84.1%)

106

76

(73.1%)

(73.8%)

>0.99

61/128

90/156

(47.7%)

(57.7%)

58

37

(40.0%)

(35.2%)

(2017) Weber R et

145

105

0.952

5/131

2/160

(3.8%)

(1.1%)

0.444

5

6

(3.5%)

(5.9%)

0.25

0.387

16/131

13/160

(12.2%)

(8.1%)

46

28

(37.1%)

(26.7%)

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al.

N/D

0.10

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Coutinho

(2017)

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MT, mechanical thrombectomy; IVT, intravenous thrombolysis; TICI, thrombolysis in cerebral infarction; TIMI, thrombolysis in myocardial infarction; mRS, modified Rankin score; sICH, symptomatic intracranial hemorrhage; N/S, not significant; NOS, not otherwise specified; SR, stent retriever; SD, suction device; OR, odds ratio;

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N/D, not described

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0.32

0.338

ACCEPTED MANUSCRIPT Preceding use of IVT before MT did not facilitate successful reperfusion

2.

Preceding use of IVT was not an independent predictor of favorable outcome

3.

MT alone can be safe and achieved favorable outcomes in patients with AIS

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1.

ACCEPTED MANUSCRIPT Abbreviations and Acronyms IVT: Intravenous thrombolysis MT: Mechanical thrombectomy LVO: Large vessel occlusion

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sICH: Symptomatic intracranial hemorrhage AIS: Acute ischemic stroke TICI: Thrombolysis in Cerebral Infarction

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RCT : Randomized control trial

ACCEPTED MANUSCRIPT Conflict of interest statement: The authors declare that the article content was composed in the absence of any

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commercial or financial relationships that could be construed as a potential conflict of interest.