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Original Article
Neurology Effectiveness of intravenous thrombolysis in patients with large-vessel occlusion receiving endovascular treatment in Korea
Min Kim1orcid, Ji Sung Lee2orcid, Seong-Joon Lee1orcid, So Young Park1orcid, Jungyun Seo1orcid, Ji Man Hong1orcid, Hee-Kwon Park3orcid, Jae-Kwan Cha4orcid, Jeffrey L. Saver5orcid, Jin Soo Lee1orcid

DOI: https://doi.org/10.4266/acc.004248
Published online: April 11, 2025

1Department of Neurology, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea

2Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

3Department of Neurology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea

4Department of Neurology, Dong-A University Hospital, Dong-A University School of Medicine, Busan, Korea

5Department of Neurology, David Geffen School of Medicine at UCLA, UCLA Comprehensive Stroke and Vascular Neurology Program, Los Angeles, CA, USA

Corresponding author: Jin Soo Lee Department of Neurology, Ajou University School of Medicine, 206 World cup-ro, Yeongtong-gu, Suwon 16499, Korea Tel: +82-31-219-5175 Fax: +82-31-219-5178 E-mail: jinsoo22@gmail.com
• Received: November 7, 2024   • Revised: February 2, 2025   • Accepted: February 19, 2025

© 2025 The Korean Society of Critical Care Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background
    The effectiveness of intravenous tissue plasminogen activator (IV tPA) in patients with large-vessel occlusion (LVO) receiving endovascular treatment (EVT) for acute ischemic stroke (AIS) has been questioned. We investigated IV tPA effectiveness in real-world AIS patients, including those with intracranial LVO receiving EVT.
  • Methods
    We identified patients with AIS who presented to hospital with National Institutes of Health Stroke Scale ≥4 within 8 hours of symptom onset from the institutional stroke registry. The association of IV tPA use with effectiveness and safety outcomes was analyzed in overall enrolled AIS patients; LVO patients; and patients treated with EVT. The effect of IV tPA was assessed using multiple logistic regression.
  • Results
    Among the 654 patients meeting study entry criteria, 238 (36.4%) received IV tPA and 416 (63.6%) did not. Multiple logistic regression analysis and shift analysis revealed IV tPA was associated with improved outcomes in overall enrolled AIS population, LVO, and EVT-treated subgroups. Among EVT-treated patients, IV tPA was associated with higher likelihood of ambulatory or better outcome (modified Rankin Scale 0–3) with odds ratio of 1.95 (P=0.03).
  • Conclusions
    In this real-world study, IV tPA use was associated with improved outcomes for patients with AIS, including among LVO patients treated and not treated with EVT, in the contemporary mechanical thrombectomy era.
  • Key Words: ischemic stroke; prognosis; stroke; thrombectomy; thrombolytic therapy
Intravenous tissue plasminogen activator (IV tPA) has been approved and used for a long time as a treatment for acute ischemic stroke (AIS) [1,2]. In the case of AIS caused by intracranial large-vessel occlusion (LVO), endovascular treatment (EVT) based on mechanical thrombectomy was approved several years previously [3-6], and its indications are gradually expanding [7-10]. However, several clinical trials have questioned the effectiveness of IV tPA in patients with LVO receiving EVT. Some of these trials have shown the noninferiority of EVT alone to IV tPA prior to EVT [11-16]. Meta-analyses of the six clinical trials demonstrated that in terms of noninferiority, there were distinct results between defining its margin as 10% and 5%. The former showed noninferiority whereas the latter did not prove noninferiority [17-19].
These clinical studies have limitations compared to real-world practice. One of the most important differences was that only patients whose EVT criteria were eligible and those who were directly transferred to a thrombectomy-capable center (mothership transfer) were included in those clinical trials. In real-world clinical settings, a non-negligible number of patients are first brought to a primary stroke center and then transferred, and many patients with LVO are ineligible for EVT [20]. Moreover, EVT failure to achieve sufficient reperfusion exists in 12%–41% of EVT-eligible patients with AIS [21,22], and if IV tPA is not administered, AIS treatment cannot be provided among the patients.
In this study, the effectiveness of IV tPA was evaluated in real-world practice, particularly during the contemporary EVT era. To evaluate several different settings, we stratified the analysis groups from patients with mild-to-moderate AIS with or without LVO to those with AIS with LVO and EVT.
Study Participants
This retrospective, single-center observational study was approved by the Institutional Review Board of Ajou University Hospital (No. AJOUIRB-DB-2023-240), and conducted in accordance with the Declaration of Helsinki. The requirement for informed consent was waived owing to the retrospective nature of this study.
Patient data were obtained from an institutional stroke registry containing information on all patients admitted with ischemic stroke at from January 2018 to February 2022. Based on local rules, a thrombolysis code (a warming call for thrombectomy) is activated for patients who arrive at the emergency room (ER) within 8 hours of the first abnormal neurological symptoms. Relevant indications for activation of the thrombolysis code are two or more consecutive unilateral hemiplegia of the face, arms, and legs, aphasia, and loss of consciousness without other clear causes within 8 hours from onset to arrival in the ER [23]. Any medical personnel in the ER can activate the code immediately after evaluating symptoms and time. To include patients who received IV tPA before transfer, we considered those presenting within 8 hours of symptom onset. Also, IV tPA and EVT were performed following the guidelines of the Korean Stroke Society (Supplementary Tables 1 and 2).
In total, 2,777 patients with activated thrombolysis codes were included in this study period; however, 1,690 patients without ischemic stroke were excluded. The diagnosis of ischemic stroke was confirmed by magnetic resonance imaging. Patients with a National Institutes of Health Stroke Scale (NIHSS) score of <4 and those with a premorbid modified Rankin Scale (mRS) score of ≥3 were excluded for prognostic evaluation (Figure 1). Patients eligible for the hyperacute period received IV tPA and/or EVT. If ineligible for recanalization therapy, patients received antiplatelet agents or anticoagulants according to the tentative stroke etiology in the early period.
Clinical Outcomes and Variables
The effectiveness of IV tPA was evaluated by comparing patients from stratified populations: all enrolled patients, patients with LVO, and patients with EVT. The time from symptom onset to hospital arrival, also known as the onset-to-door time, was recorded based on the patients’ report of the time they first observed stroke symptoms or the time that a witness observed the onset of symptoms. The NIHSS score was determined during initial assessment in the emergency department. “EVT” referred to all cases in which EVT was performed, regardless of successful reperfusion. “Transfer” referred to cases that were transferred from primary stroke centers to our hospital, regardless of whether IV tPA was administered. Corresponding vessel occlusion was evaluated by computed tomography angiography performed in the ER. LVO was defined as occlusion of the intracranial internal carotid artery (ICA), M1 segment of the middle cerebral artery (MCA), and basilar artery, including tandem occlusion [24]. The clinical outcomes were assessed using the mRS at 3 months. Excellent, good, favorable, and poor outcomes were defined as mRS scores of 0–1, 0–2, 0–3, and 5–6, respectively. In addition, the frequency and severity of hemorrhagic transformation was examined in patients with EVT using the hemorrhagic transformation classification [25]. We evaluated the prognosis as excellent, good, and favorable clinical outcomes for all enrolled patients, patients with LVO, and patient with EVT respectively, considering patient severity by group. The patients' outcome was evaluated through both dichotomous and shift analyses, after adjusting covariates such as age (per 10 years), sex, initial NIHSS, onset-to-door time (per 1 hours), transfer, and risk factors [26].
Statistical Analyses
Values are presented as mean±standard deviation, median (interquartile range) for continuous variables, or as the number (%) of subjects for categorical variables. To compare the two groups, Student t-test and the Wilcoxon rank sum test were used for continuous variables, whereas the chi-squared test, Fisher’s exact test, and Cochran-Mantel-Haenszel shift test were used for categorical variables. Multiple binary logistic regression was used to identify the predictors of outcomes, including clinically relevant variables as age (per 10-year increase), sex, initial NIHSS, onset to door time (per 1 hour increase), vessel occlusion, transfer, risk factor, EVT, and IV tPA, and associations were reported as odds ratios (ORs) with corresponding 95% CIs. We conducted ordinal logistic regression to assess the differences in the distribution of 3-month mRS between the two groups.
Statistical analyses were performed using the R statistical software version 3.6.3 (R Foundation for Statistical Computing) and SAS version 9.4 (SAS Institute Inc.) and a P-value <0.05 was considered statistically significant.
Overall Enrolled Patients
This study included 654 patients with ischemic stroke, of whom 238 received IV tPA and 416 did not. The patients who received IV tPA were younger (70 vs. 67 years, P=0.004) and had a higher proportion of males (59.1% vs. 68.5%, P=0.02) than those who did not. The onset-to-door time was significantly faster in the IV tPA group than in the non-IV tPA group (148 minutes vs. 71 minutes, P<0.001). However, there were no significant differences between the two groups in terms of the initial NIHSS score and the frequencies of LVO. The IV tPA group showed lower median 3-month mRS scores (2 [1–3] vs. 3 [1–5], P<0.001) and mortality rates (6.3% vs. 13.2%, P=0.006). The frequency of transfer did not significantly differ between the two groups. Characteristics and outcomes of the enrolled patients are summarized in Table 1. In the multivariable analysis model, IV tPA was an independent predictor of excellent clinical outcomes (OR, 2.5; 95% CI, 1.60–3.91; P<0.001) (Table 1). Shift analysis of the mRS after adjusting confounders showed a significantly lower score in patients with IV tPA (adjusted common OR, 2.75; 95% CI, 1.99–3.78; P<0.001) (Figure 2A).
Patients with LVO
This subgroup included 301 patients with AIS and LVO, with 110 and 191 receiving and not IV tPA, respectively. The IV tPA group had a higher proportion of male patients and a significantly faster onset-to-door time compared with the non-IV tPA group. There were no significant differences in the initial NIHSS score, mortality, or frequency of transfer from other hospitals between the two groups. The IV tPA group also had a higher incidence rate of EVT than the non-IV tPA group. The median 3-month mRS score was significantly lower in the IV tPA group compared with the non-IV tPA group (4 [2–5] vs. 3 [1–4], P<0.001). Univariate analysis showed that EVT (OR, 2.19; 95% CI, 1.22–3.91; P=0.009) and IV tPA (OR, 2.31; 95% CI, 1.41–3.76; P<0.001) was predictors of favorable clinical outcomes. Multivariable analysis showed that IV tPA (OR, 2.63; 95% CI, 1.41–4.91; P=0.001) was an independent predictor. The characteristics and outcomes of the patients with LVO are summarized in Table 2. The shift analysis of the 3-month mRS after adjusting confounders showed a better prognosis in patients treated with IV tPA (adjusted common OR, 2.67; 95% CI, 1.66–4.29; P<0.001) (Figure 2B). Representative cases, whose LVO stroke treatment was helped by IV tPA, were illustrated in Figure 3.
Patients with EVT
This subgroup consisted of 293 patients with AIS who treated EVT, with 177 receiving IV tPA and 116 not receiving. In this subgroup analysis, patients who received IV tPA had a higher initial NIHSS score (16 [11-19] vs. 17 [13-21], P=0.01) and a shorter time from onset to hospital arrival than those who did not receive IV tPA. Despite initial stroke severity, patients who received IV tPA had better outcomes as assessed by 3-month mRS score compared with those who did not receive IV tPA (3 [2–5] vs. 3 [1–4], P=0.01) (Table 3). There was no statistically significant difference in the occurrence of hemorrhagic transformation between the two groups (48.59% vs. 44.83%, P=0.61) (Table 3). In the multivariable analysis, IV tPA was also associated with a favorable outcome (OR, 1.95; 95% CI, 1.07–3.56; P=0.023) (Table 3). Moreover, the shift analysis of the 3-month mRS after adjusting confounders showed a significantly lower score in patients who received IV tPA (adjusted common OR, 2.33; 95% CI, 1.47–3.71; P<0.001) (Figure 2C).
Our real-world study demonstrates IV tPA effectiveness in non-mild AIS patients, including those with LVO, regardless of EVT treatment. We evaluated their effectiveness in patients stratified into subpopulations according to (1) overall AIS with NIHSS > 4, (2) LVO, and (3) EVT using logistic regression analyses and shift analyses. Specifically, IV tPA was associated with improved outcomes in patients receiving EVT, emphasizing that fibrinolytic therapy is still important in patients with LVO who are eligible for EVT.
Several clinical trials have recently demonstrated the noninferiority of EVT alone to intravenous thrombolysis prior to EVT in patients with LVO. However, guidelines following these trials did not demonstrate noninferiority from systematic analyses [17,18]. Apart from the systematic analyses, the population in these clinical trials was narrow in that patients directly transferred to thrombectomy centers were mostly included. Importantly, not all patients with AIS initially present to a thrombectomy-capable or comprehensive stroke center. When transfer time is prolonged or transfer distance is greater when transferring from the primary stroke center, the drip-and-ship strategy may be preferred over the mothership strategy [27]. On this basis, even if noninferiority was proven in those trials, it cannot be generalized to overall patients with LVO. On the other hand, even in EVT-eligible patients, EVT may fail for various reasons [21,22]. In these cases, the administration of IV tPA is the only option for reperfusion and can potentially improve patient prognosis. Although recanalization rates were not that high in LVO (ICA terminus occlusion, 4.4%; MCA M1 occlusion, 32.3%) causing AIS by IV tPA, a previous Canadian study reported that the efficacy predicting 3-month mRS score 0–2 was evident (OR, 2.7; 95% CI 1.5–4.5; P<0.001) in multivariable analysis if a recanalization was achieved by IV tPA [28].
There are several potential explanations for our study results regarding the good prognosis of patients with AIS receiving IV tPA, including patients with LVO. First, as described above, it is possible that occluded vessels were opened by thrombolysis of blood clots in patients with LVO from IV tPA treatment [29-31]. Although the recanalization rate of the terminal ICA after IV tPA administration in LVO is generally low, higher recanalization rates of approximately 30%–44% have been reported in the M1 and M2 segments of the MCA [31]. In patients with stroke resulting from occlusion in the M2/M3 segments of the MCA, A2/A3 segments of the anterior cerebral artery, and P2/P3 segments of the posterior cerebral artery, where the effectiveness of EVT has not been fully established, tPA remains an effective treatment for acute stroke patients. Previous study demonstrated that administering IV tPA to patients with medium vessel occlusions who did not receive EVT resulted in early recanalization in 42% of patients, which was associated with excellent functional outcomes [32]. Although this study did not confirm a direct association between IV tPA and functional outcomes, it is possible that IV tPA may indirectly contribute to better functional recovery as the rate of early recanalization was higher in patients who received IV tPA [29,32]. In addition, another study suggested that EVT provided therapeutic effects comparable to IVT alone in patients with acute M2 segment MCA occlusion [33].
Second, IV tPA may reduce the thrombus or clot size because distal thrombus migration often occurs after IV tPA. Although thrombus migration, which occurs before EVT, may reduce complete reperfusion from EVT, thrombus migration is associated with better functional outcomes [34]. The occurrence of distal thrombus migration during EVT suggests that the thrombus may be fragile [34,35]. This is thought to be attributed to the fact that large clots cause ischemia in a larger brain area, whereas small clots cause ischemia in a smaller brain area. Additionally, evidence suggests that administering IV tPA before EVT can result in higher rates of recanalization than EVT alone [36,37].
Third, IV tPA can affect venous outflow in patients with AIS. IV tPA is associated with favorable venous outflow [38]. They may reduce microvascular thrombosis in both arterioles and venules through improved venous outflow, leading to slower progression of the ischemic core, smaller ischemic core and final infarct volumes, and higher likelihood of successful vessel reperfusion in patients with AIS [38]. A recent randomized control trial demonstrated that intra-arterial tPA following mechanical thrombectomy improved clinical outcomes in patients with successful reperfusion, and the improvement was attributed to the amelioration of microcirculatory reperfusion [39]. Therefore, IV tPA may be effective for patients with LVO, regardless of the recanalization of thrombus owing to its potential to improve microcirculatory reperfusion and other factors. These findings are supported by experiments using rodent stroke models. In rats with cerebral ischemia induced by a filament in the MCA, significant blood flow obstruction was observed in small arteries and veins, and tPA administration resulted in a reduction in arterial, capillary, and venous thromboses [40].
Forth, despite favorable indications for EVT, its failure can occur due to various reasons. A meta-analysis of individual patients undergoing EVT with Solitaire in randomized controlled trials indicated a success rate of 71.1% [41]. However, this means that 28.9% of cases still experienced unsuccessful EVT. Despite technological advancements leading to increasing recanalization rates, EVT failure could occur due to various factors such as anatomical complexities, large clot burdens, tandem occlusions, clot characteristics, and diverse pathomechanisms [21]. Failure to reach the thrombus during reperfusion can result in access failure. The reported proportion of access failure among all EVT failures varies across studies, but typically falls within the range of about 20%–30% [42,43]. Opting for direct EVT without prior IVT in these cases may lead to missed opportunities for acute stroke treatment.
Our study has some limitations. First, this was a single-center, retrospective study; thus, it could not be simply generalized. Hence, a multicenter study to obtain more concrete results is required. Second, this study indicated better outcomes in patients who received LVO treatment with IV tPA; however, the detailed mechanism remains unclear based on the current study design. Further investigations are necessary to determine the cause by examining factors, such as the rate of recanalization, clot migration, and the degree of microcirculation, in collaboration with primary or transfer hospitals. Third, patients who receive IV tPA may have certain characteristics that predispose them to a better prognosis. It was observed that patients who received IV tPA had a shorter onset-to-door time, which may have influenced their outcomes. To mitigate this effect, we adjusted the temporal variables using multivariable analysis.
In conclusion, IV tPA showed evidence of effectiveness in real-world practice for patients with AIS, including those with LVO receiving EVT. These results support the use of IV tPA in all non-mild patients meeting lytic treatment criteria, including among LVO patients treated and not treated with EVT.
▪ Recent clinical trials have demonstrated that endovascular thrombectomy (EVT) alone was not inferior to EVT preceded by intravenous tissue plasminogen activator (IV tPA).
▪ However, in this real-world study, the use of IV tPA was associated with improved outcomes in patients with non-mild acute ischemic stroke.
▪ These positive outcomes were observed both in large vessel occlusion patients who received EVT and those who did not.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Conceptualization: MK, JSL (Jin Soo Lee). Methodology: MK, JSL (Ji Sung Lee), HKP, JKC, JSL (Jin Soo Lee). Formal analysis: MK, JSL (Ji Sung Lee), SYP, JSL (Jin Soo Lee). Data curation: MK, SJL, SYP, JMH, JSL (Jin Soo Lee), JS. Visualization: MK, JSL (Ji Sung Lee), JSL (Jin Soo Lee). Project administration: MK, SYP, JMH, HKP, JKC, JSL (Jin Soo Lee). Writing - original draft: MK, JSL (Jin Soo Lee). Writing - review & editing: all authors. All authors read and agreed to the published version of the manuscript.

Supplementary materials can be found via https://doi.org/10.4266/acc.004248.
Supplementary Table 1.
Indications for intravenous thrombolysis (as recommended by the Korean Stroke Society)
acc-004248-Supplementary-Table-1.pdf
Supplementary Table 2.
Recommendations on ERT in patients with acute ischemic stroke (as recommended by the Korean Stroke Society)
acc-004248-Supplementary-Table-2.pdf
Figure 1.
Study flowsheet. NIHSS: National Institutes of Health Stroke Scale; mRS: modified Rankin Scale.
acc-004248f1.jpg
Figure 2.
Distributions of modified Rankin Scale score at 3 months–Shift analysis. Modified Rankin Scale score at 3 months in (A) the overall enrolled population, (B) patients with large vessel occlusion, and (C) patients receiving endovascular treatment. IV tPA: intravenous tissue plasminogen activator; OR: odds ratio.
acc-004248f2.jpg
Figure 3.
Cases that improved after intravenous (IV) thrombolysis. (A) IV infusion of tissue plasminogen activator (tPA) before transfer. A 62-year-old male patient presented with left hemiplegia and right gaze deviation, receiving IV tPA in a primary center. As soon as received, he was transferred to an endovascular thrombectomy (EVT)-capable stroke center. A computed tomography angiography revealed a right M1 segment occlusion of middle cerebral artery in emergency room (ER). Subsequent transfemoral cerebral angiography prior to EVT demonstrated recanalization in the right M1 and remnant clot was migrated into M3 segment. The patient, initially presenting with a National Institute of Health Stroke Scale (NIHSS) score of 11 in the ER of the EVT-capable center, improved to NIHSS 1 upon discharge. The 3-month follow-up modified Rankin Scale (mRS) score was 0. (B) IV tPA infusion in a case of unavailable EVT. A 69-year-old male patient with an isolated occlusion in the right internal carotid artery (ICA) with its bifurcation saved and another occlusion in anterior communicating artery presented with right major hemispheric syndrome (an NIHSS score of 15). IV tPA was infused in the ER, and the patient was brought to EVT room. During EVT, the occlusion in the right ICA was ascertained as a chronic status because wire could not be passed any further. On angiography for left ICA, fortunately, the occlusion in the anterior communicating artery was shown to be recanalized. Probably, blood supply to the right hemisphere has been collateralized by the left ICA via the anterior communicating artery prior to the index stroke, and the new occlusion in the anterior communicating artery might have caused substantial perfusion defect in the right hemisphere. The patient was discharged with an NIHSS score of 6. The mRS score measured at the 3-month follow-up was 1.
acc-004248f3.jpg
Table 1.
Comparative and multivariable analyses in the enrolled patients
Variable Non-IV tPA(n=416) IV tPA(n=238) P-value Multivariable analysis for 3-month mRS score 0–1
Odds ratio (95% CI) P-value
Age (yr) 70±13 67±14 0.004 0.61 (0.51–0.73) <0.001
Sex, male 246 (59.1) 163 (68.5) 0.02 1.33 (0.85–2.07) 0.21
Initial NIHSS score 12 (6–19) 13 (7–18) 0.51 0.81 (0.78–0.85) <0.001
Onset-to-door time (min) 148 (79–284) 71 (47–136) <0.001 0.91 (0.80–1.03) 0.12
Large-vessel occlusion 191 (45.9) 110 (46.2) 0.94 0.94 (0.46–1.90) 0.85
IV tPA infusion - - - 2.50 (1.60–3.91) <0.001
Endovascular treatment 177 (42.5) 116 (48.7) 0.13 0.97 (0.52–1.82) 0.93
3-Month mRS score 3 (1–5) 2 (1–3) <0.001 - -
Excellent clinical outcomes (mRS 0–1) 125 (30.0) 117 (49.2) <0.001 - -
Poor clinical outcomes (mRS 5–6) 109 (26.2) 152 (63.9) <0.001 - -
3-Month mortality 55 (13.2) 15 (6.3) 0.01 - -
Transfer 83 (20.0) 48 (20.2) 0.95 0.54 (0.31–0.94) 0.03
Risk factor
 HTN 272 (65.4) 135 (56.7) 0.03 0.88 (0.57–1.36) 0.57
 DM 137 (32.9) 60 (25.2) 0.04 0.88 (0.56–1.37) 0.56
 Dyslipidemia 153 (36.8) 94 (39.5) 0.49 0.70 (0.46–1.06) 0.09
 CAOD 42 (10.1) 23 (9.7) 0.86 0.58 (0.29–1.16) 0.12
 Smoking 89 (21.4) 55 (23.1) 0.61 0.69 (0.41–1.16) 0.17
 A-fib 136 (32.7) 92 (38.7) 0.12 1.54 (0.98–2.43) 0.06

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

IV tPA: intravenous tissue plasminogen activator; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; HTN: hypertension; DM: diabetes mellitus; CAOD: coronary artery occlusive disease; A-fib: atrial fibrillation.

Table 2.
Comparative and multivariable analyses in patients with LVO
Variable Non-IV tPA(n=191) IV tPA(n=110) P-value Multivariable analysis for 3-month mRS score 0–3
Odds ratio (95% CI) P-value
Age (yr) 70±13 67±15 0.04 0.76 (0.60–0.97) 0.02
Sex, male 110 (57.6) 77 (70.0) 0.03 0.71 (0.39–1.28) 0.25
Initial NIHSS score 17 (12–20) 17 (12–21) 0.19 0.84 (0.80–0.89) <0.001
Onset-to-door time (min) 120 (71–218) 68 (44–120) <0.001 0.96 (0.80–1.15) 0.64
Occlusion location 0.79 -
 Intracranial ICA 51 (26.7) 28 (25.5) -
 MCA M1 92 (48.2) 54 (49.1) -
 BA 20 (10.5) 15 (13.6) -
 Tandem 28 (14.7) 13 (11.8) -
IV tPA infusion 2.63 (1.41–4.91) 0.002
Endovascular treatment 145 (75.9) 97 (88.2) 0.01 2.08 (0.98–4.42) 0.06
3-Month mRS score 4 (2–5) 3 (1–4) <0.001 - -
Favorable clinical outcome (mRS 0–3) 90 (47.1) 74 (67.3) <0.001 - -
Poor clinical outcome (mRS 5–6) 67 (35.1) 22 (20.0) 0.01 - -
3-Month mortality 34 (17.8) 11 (10.0) 0.07 - -
Transfer 42 (22.0) 24 (21.8) 0.97 0.57 (0.28–1.17) 0.13
Risk factor
 HTN 122 (63.9) 55 (50.0) 0.02 0.80 (0.43–1.47) 0.46
 DM 57 (29.8) 21 (19.1) 0.04 0.69 (0.34–1.38) 0.29
 Dyslipidemia 67 (35.1) 37 (33.6) 0.80 1.34 (0.73–2.44) 0.35
 CAOD 23 (12.0) 9 (8.2) 0.30 0.75 (0.32–1.78) 0.51
 Smoking 40 (20.9) 25 (22.7) 0.72 2.23 (1.05–4.71) 0.04
 A-fib 71 (37.2) 52 (47.3) 0.09 1.19 (0.66–2.14) 0.56

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

LVO: large-vessel occlusion; IV tPA: intravenous tissue plasminogen activator; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; MCA: middle cerebral artery; BA: basilar artery; HTN: hypertension; DM: diabetes mellitus; CAOD: coronary artery occlusive disease; A-fib: atrial fibrillation.

Table 3.
Comparative and multivariable analyses in patients receiving endovascular treatment
Variable Non-IV tPA(m=177) IV tPA(n=116) P-value Multivariable analysis for 3-month mRS score 0–3
Odds ratio (95% CI) P value
Age (yr) 71±12 67.5±15.7 0.08 0.71 (0.56–0.90) 0.004
Sex, male 104 (58.8) 79 (68.1) 0.11 0.79 (0.44–1.40) 0.41
Initial NIHSS 16 (11–19) 17 (13–21) 0.01 0.85 (0.80–0.90) <0.001
Onset-to-door time (min) 116 (65–210) 65 (44–116) <0.001 0.96 (0.81–1.15) 0.68
Onset-to-puncture time (min) 264 (187–388) 175 (137–219) <0.001
IV tPA infusion 1.95 (1.07–3.56) 0.03
3-Months mRS score 3 (2–5) 3 (1–4) 0.01 - -
Favorable clinical outcome (mRS 0–3) 96 (54.2) 76 (65.5) 0.05 - -
Poor clinical outcomes (mRS 5–6) 53 (29.9) 25 (21.6) 0.11 - -
3-Month mortality 27 (15.3) 13 (11.2) 0.32 - -
HT 86 (48.59) 52 (44.83) 0.61 - -
Classification of HT 0.79 -
 HT1 28 (32.56) 21 (40.38) -
 HT2 38 (44.19) 19 (36.54) -
 PH1 11 (12.79) 7 (13.46) -
 PH2 9 (10.47) 5 (9.62) -
Transfer 37 (20.9) 22 (19.0) 0.69 0.65 (0.32–1.32) 0.23
Risk factor
 HTN 118 (66.7) 61 (52.6) 0.02 0.75 (0.41–1.36) 0.34
 DM 55 (31.1) 24 (20.7) 0.05 0.80 (0.42–1.54) 0.51
 Dyslipidemia 68 (38.4) 40 (34.5) 0.50 1.08 (0.61–1.93) 0.79
 CAOD 21 (11.9) 9 (7.8) 0.26 0.72 (0.31–1.68) 0.45
 Smoking 38 (21.5) 24 (20.7) 0.87 2.32 (1.08–4.95) 0.03
 A-fib 74 (41.8) 57 (49.1) 0.22 1.62 (0.91–2.88) 0.10

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

IV tPA: intravenous tissue plasminogen activator; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; HT: hemorrhagic transformation; HTN: hypertension; DM: diabetes mellitus; CAOD: coronary artery occlusive disease; A-fib: atrial fibrillation.

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      Effectiveness of intravenous thrombolysis in patients with large-vessel occlusion receiving endovascular treatment in Korea
      Image Image Image
      Figure 1. Study flowsheet. NIHSS: National Institutes of Health Stroke Scale; mRS: modified Rankin Scale.
      Figure 2. Distributions of modified Rankin Scale score at 3 months–Shift analysis. Modified Rankin Scale score at 3 months in (A) the overall enrolled population, (B) patients with large vessel occlusion, and (C) patients receiving endovascular treatment. IV tPA: intravenous tissue plasminogen activator; OR: odds ratio.
      Figure 3. Cases that improved after intravenous (IV) thrombolysis. (A) IV infusion of tissue plasminogen activator (tPA) before transfer. A 62-year-old male patient presented with left hemiplegia and right gaze deviation, receiving IV tPA in a primary center. As soon as received, he was transferred to an endovascular thrombectomy (EVT)-capable stroke center. A computed tomography angiography revealed a right M1 segment occlusion of middle cerebral artery in emergency room (ER). Subsequent transfemoral cerebral angiography prior to EVT demonstrated recanalization in the right M1 and remnant clot was migrated into M3 segment. The patient, initially presenting with a National Institute of Health Stroke Scale (NIHSS) score of 11 in the ER of the EVT-capable center, improved to NIHSS 1 upon discharge. The 3-month follow-up modified Rankin Scale (mRS) score was 0. (B) IV tPA infusion in a case of unavailable EVT. A 69-year-old male patient with an isolated occlusion in the right internal carotid artery (ICA) with its bifurcation saved and another occlusion in anterior communicating artery presented with right major hemispheric syndrome (an NIHSS score of 15). IV tPA was infused in the ER, and the patient was brought to EVT room. During EVT, the occlusion in the right ICA was ascertained as a chronic status because wire could not be passed any further. On angiography for left ICA, fortunately, the occlusion in the anterior communicating artery was shown to be recanalized. Probably, blood supply to the right hemisphere has been collateralized by the left ICA via the anterior communicating artery prior to the index stroke, and the new occlusion in the anterior communicating artery might have caused substantial perfusion defect in the right hemisphere. The patient was discharged with an NIHSS score of 6. The mRS score measured at the 3-month follow-up was 1.

      Figure 1.

      Figure 2.

      Figure 3.

      Effectiveness of intravenous thrombolysis in patients with large-vessel occlusion receiving endovascular treatment in Korea
      Variable Non-IV tPA(n=416) IV tPA(n=238) P-value Multivariable analysis for 3-month mRS score 0–1
      Odds ratio (95% CI) P-value
      Age (yr) 70±13 67±14 0.004 0.61 (0.51–0.73) <0.001
      Sex, male 246 (59.1) 163 (68.5) 0.02 1.33 (0.85–2.07) 0.21
      Initial NIHSS score 12 (6–19) 13 (7–18) 0.51 0.81 (0.78–0.85) <0.001
      Onset-to-door time (min) 148 (79–284) 71 (47–136) <0.001 0.91 (0.80–1.03) 0.12
      Large-vessel occlusion 191 (45.9) 110 (46.2) 0.94 0.94 (0.46–1.90) 0.85
      IV tPA infusion - - - 2.50 (1.60–3.91) <0.001
      Endovascular treatment 177 (42.5) 116 (48.7) 0.13 0.97 (0.52–1.82) 0.93
      3-Month mRS score 3 (1–5) 2 (1–3) <0.001 - -
      Excellent clinical outcomes (mRS 0–1) 125 (30.0) 117 (49.2) <0.001 - -
      Poor clinical outcomes (mRS 5–6) 109 (26.2) 152 (63.9) <0.001 - -
      3-Month mortality 55 (13.2) 15 (6.3) 0.01 - -
      Transfer 83 (20.0) 48 (20.2) 0.95 0.54 (0.31–0.94) 0.03
      Risk factor
       HTN 272 (65.4) 135 (56.7) 0.03 0.88 (0.57–1.36) 0.57
       DM 137 (32.9) 60 (25.2) 0.04 0.88 (0.56–1.37) 0.56
       Dyslipidemia 153 (36.8) 94 (39.5) 0.49 0.70 (0.46–1.06) 0.09
       CAOD 42 (10.1) 23 (9.7) 0.86 0.58 (0.29–1.16) 0.12
       Smoking 89 (21.4) 55 (23.1) 0.61 0.69 (0.41–1.16) 0.17
       A-fib 136 (32.7) 92 (38.7) 0.12 1.54 (0.98–2.43) 0.06
      Variable Non-IV tPA(n=191) IV tPA(n=110) P-value Multivariable analysis for 3-month mRS score 0–3
      Odds ratio (95% CI) P-value
      Age (yr) 70±13 67±15 0.04 0.76 (0.60–0.97) 0.02
      Sex, male 110 (57.6) 77 (70.0) 0.03 0.71 (0.39–1.28) 0.25
      Initial NIHSS score 17 (12–20) 17 (12–21) 0.19 0.84 (0.80–0.89) <0.001
      Onset-to-door time (min) 120 (71–218) 68 (44–120) <0.001 0.96 (0.80–1.15) 0.64
      Occlusion location 0.79 -
       Intracranial ICA 51 (26.7) 28 (25.5) -
       MCA M1 92 (48.2) 54 (49.1) -
       BA 20 (10.5) 15 (13.6) -
       Tandem 28 (14.7) 13 (11.8) -
      IV tPA infusion 2.63 (1.41–4.91) 0.002
      Endovascular treatment 145 (75.9) 97 (88.2) 0.01 2.08 (0.98–4.42) 0.06
      3-Month mRS score 4 (2–5) 3 (1–4) <0.001 - -
      Favorable clinical outcome (mRS 0–3) 90 (47.1) 74 (67.3) <0.001 - -
      Poor clinical outcome (mRS 5–6) 67 (35.1) 22 (20.0) 0.01 - -
      3-Month mortality 34 (17.8) 11 (10.0) 0.07 - -
      Transfer 42 (22.0) 24 (21.8) 0.97 0.57 (0.28–1.17) 0.13
      Risk factor
       HTN 122 (63.9) 55 (50.0) 0.02 0.80 (0.43–1.47) 0.46
       DM 57 (29.8) 21 (19.1) 0.04 0.69 (0.34–1.38) 0.29
       Dyslipidemia 67 (35.1) 37 (33.6) 0.80 1.34 (0.73–2.44) 0.35
       CAOD 23 (12.0) 9 (8.2) 0.30 0.75 (0.32–1.78) 0.51
       Smoking 40 (20.9) 25 (22.7) 0.72 2.23 (1.05–4.71) 0.04
       A-fib 71 (37.2) 52 (47.3) 0.09 1.19 (0.66–2.14) 0.56
      Variable Non-IV tPA(m=177) IV tPA(n=116) P-value Multivariable analysis for 3-month mRS score 0–3
      Odds ratio (95% CI) P value
      Age (yr) 71±12 67.5±15.7 0.08 0.71 (0.56–0.90) 0.004
      Sex, male 104 (58.8) 79 (68.1) 0.11 0.79 (0.44–1.40) 0.41
      Initial NIHSS 16 (11–19) 17 (13–21) 0.01 0.85 (0.80–0.90) <0.001
      Onset-to-door time (min) 116 (65–210) 65 (44–116) <0.001 0.96 (0.81–1.15) 0.68
      Onset-to-puncture time (min) 264 (187–388) 175 (137–219) <0.001
      IV tPA infusion 1.95 (1.07–3.56) 0.03
      3-Months mRS score 3 (2–5) 3 (1–4) 0.01 - -
      Favorable clinical outcome (mRS 0–3) 96 (54.2) 76 (65.5) 0.05 - -
      Poor clinical outcomes (mRS 5–6) 53 (29.9) 25 (21.6) 0.11 - -
      3-Month mortality 27 (15.3) 13 (11.2) 0.32 - -
      HT 86 (48.59) 52 (44.83) 0.61 - -
      Classification of HT 0.79 -
       HT1 28 (32.56) 21 (40.38) -
       HT2 38 (44.19) 19 (36.54) -
       PH1 11 (12.79) 7 (13.46) -
       PH2 9 (10.47) 5 (9.62) -
      Transfer 37 (20.9) 22 (19.0) 0.69 0.65 (0.32–1.32) 0.23
      Risk factor
       HTN 118 (66.7) 61 (52.6) 0.02 0.75 (0.41–1.36) 0.34
       DM 55 (31.1) 24 (20.7) 0.05 0.80 (0.42–1.54) 0.51
       Dyslipidemia 68 (38.4) 40 (34.5) 0.50 1.08 (0.61–1.93) 0.79
       CAOD 21 (11.9) 9 (7.8) 0.26 0.72 (0.31–1.68) 0.45
       Smoking 38 (21.5) 24 (20.7) 0.87 2.32 (1.08–4.95) 0.03
       A-fib 74 (41.8) 57 (49.1) 0.22 1.62 (0.91–2.88) 0.10
      Table 1. Comparative and multivariable analyses in the enrolled patients

      Values are presented as mean±standard deviation, number (%), or median (interquartile range).

      IV tPA: intravenous tissue plasminogen activator; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; HTN: hypertension; DM: diabetes mellitus; CAOD: coronary artery occlusive disease; A-fib: atrial fibrillation.

      Table 2. Comparative and multivariable analyses in patients with LVO

      Values are presented as mean±standard deviation, number (%), or median (interquartile range).

      LVO: large-vessel occlusion; IV tPA: intravenous tissue plasminogen activator; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; MCA: middle cerebral artery; BA: basilar artery; HTN: hypertension; DM: diabetes mellitus; CAOD: coronary artery occlusive disease; A-fib: atrial fibrillation.

      Table 3. Comparative and multivariable analyses in patients receiving endovascular treatment

      Values are presented as mean±standard deviation, number (%), or median (interquartile range).

      IV tPA: intravenous tissue plasminogen activator; mRS: modified Rankin Scale; NIHSS: National Institutes of Health Stroke Scale; HT: hemorrhagic transformation; HTN: hypertension; DM: diabetes mellitus; CAOD: coronary artery occlusive disease; A-fib: atrial fibrillation.

      Table 1.

      Table 2.

      Table 3.

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