Comparison of mechanical thrombectomy alone versus post-IV t-PA thrombectomy in acute large artery occlusion within 4.5 hours of symptom onset

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J Cerebrovasc Endovasc Neurosurg. 2025;27(4):318-326

Publication date (electronic) : 2025 August 21

doi : https://doi.org/10.7461/jcen.2025.E2025.04.004

Joonwon Lee¹, Hyungon Lee^2,*, Kyung-wan Kim³, Seung Hwan Kim⁴, Yunhyeok Choi⁵, Sung-Chul Jin^,6

¹Department of Neurology, Inje University Haeundae Paik Hospital, Busan, Republic of Korea

²Department of Neurosurgery, Haeundae Bumin Hospital, Busan, Republic of Korea

³Department of Radiology, Masan University, Changwon, Republic of Korea

⁴Department of Neurosurgery, Samsung Changwon Hospital Sungkyunkwan University School of Medicine, Changwon, Republic of Korea

⁵Department of Neurosurgery, Good Samsun Hospital, Busan, Republic of Korea

⁶Department of Neurosurgery, Inje University Haeundae Paik Hospital, Busan, Republic of Korea

Correspondence to Sung-Chul Jin Department of Neurosurgery, Inje University Haeundae Paik Hospital, 875, Haeun-daero, Haeundae-gu, Busan 48108, Republic of Korea Tel +82-51-797-0607 Fax +82-51-797-0434 E-mail kusmal@hanmail.net

*equally contributed as first author

Received 2025 April 2; Revised 2025 July 7; Accepted 2025 July 11.

Abstract

INTRODUCTION

Intravenous tissue plasminogen activator (IV t-PA) alone has been reported to achieve a successful recanalization rate of approximately 50% [11]. In contrast, mechanical thrombectomy (MT), with or without IV t-PA bridging therapy, has demonstrated a recanalization rate approaching 90% with reduced risk of thrombus migration or fragmentation [1,3,12]. As a result, IV t-PA has been adopted as a standard bridging therapy in the management of large artery occlusion within 4.5 hours of symptom onset, particularly in the era of intra-arterial recanalization therapy (IAT) [8,9]. Recent studies have shown that MT alone can yield comparable radiological outcomes to those of MT following IV t-PA in large artery occlusion beyond the 4.5-hour window [13,15]. Other trials have supported the efficacy of IV t-PA as a bridging therapy in earlier time windows [7,14].

Although IV t-PA alone may lead to complete neurological recovery in some patients, its administration in real-world practice often delays MT initiation. In our institution, treatment delays occur due to time spent evaluating post-thrombolysis improvement and limitations related to the on-call interventionalist system, as opposed to an in-house coverage model, was associated with inherent delays due to both the time required for the interventionalist to arrive at the hospital and the additional time needed to prepare for the endovascular procedure. These delays may adversely affect clinical and radiological outcomes [6]. Therefore, we implemented a critical stroke call pathway of direct communication between neurointerventionists and paramedics [5]. In addition, for patients with atherosclerotic occlusion, adjunctive antiplatelet therapy is generally contraindicated during the first 24 hours after intravenous tPA administration due to the increased risk of hemorrhagic complications [8,9]. In addition, IV t-PA may increase the risk of distal thrombus migration, making further endovascular treatment unfeasible in some cases [10]. Thus, it is important to reassess the risks and benefits of IV t-PA in the absence of bridging therapy, especially within the critical 4.5-hour therapeutic window for large artery occlusion.

Advancements in thrombectomy devices—such as balloon-guiding catheters and retrieval stents—as well as combination techniques involving suction aspiration and stent retriever deployment, have improved the likelihood of complete recanalization without thrombus fragmentation or migration during MT procedures [16].

In line with the recent American Heart Association (AHA) guidelines recommending the use of intravenous t-PA when feasible without delaying endovascular therapy, our study aimed to evaluate whether direct mechanical thrombectomy (MT) without prior IV t-PA could lead to improved time metrics and comparable or superior outcomes in real-world clinical settings in Korea. By implementing a streamlined stroke call pathway that bypasses IV t-PA, we sought to determine whether reducing door-to-puncture time could translate into better clinical outcomes. Given the limited number of randomized trials directly comparing these strategies, our study contributes important data to this ongoing debate.

Therefore, we propose that MT alone within 4.5 hours of symptom onset should be considered a viable and potentially preferable first-line treatment strategy compared to post-IV t-PA MT.

MATERIALS AND METHODS

Study cohort

From January 2018 to December 2020, 280 patients with large artery occlusion underwent MT at our hospital. Among them, 190 patients received MT within 4.5 hours of symptom onset, including those treated with IV t-PA. We excluded 53 patients who were ineligible for IV t-PA. Consequently, 137 patients were enrolled in this study and categorized into two groups: MT only (n=82, 59.8%) and post-IV t-PA MT (n=55, 40.2%) (Fig. 1).

Fig. 1.

Patients flowchart. MT, mechanical thrombectomy, IV t-PA, intravenous tissue plasminogen activator

To reduce door-to-puncture time, we implemented a critical stroke call pathway in which intravenous t-PA was intentionally omitted in eligible patients presenting within 4.5 hours of symptom onset. In contrast, under the routine stroke pathway, patients within 4.5 hours of onset who met the criteria for IV t-PA received the thrombolytic agent first. Their clinical response was then assessed by stroke neurologists. If there was no significant improvement, mechanical thrombectomy (MT) was subsequently arranged by the neurointervention team. Accordingly, patients in the MT-only group were treated via the critical stroke call pathway, whereas those in the post-IV tPA MT group followed the routine stroke pathway.

Our thrombectomy strategy, previously published, demonstrated that proximal balloon occlusion combined with hybrid mechanical thrombectomy beyond the 4.5-hour window achieved high recanalization rates with minimal distal thrombus migration in large artery occlusions [3]. Based on these findings, we hypothesized that MT alone would be sufficient within the 4.5-hour window, without necessitating IV t-PA pretreatment.

RESULTS

Among the 137 patients included in this study, 77 (56.2%) were male, with a median age of 69 years (interquartile range (IQR), 60–77). Occlusion locations included the internal carotid artery (n=21), middle cerebral artery (n=69), anterior cerebral artery (n=2), basilar artery (n=15), vertebral artery (n=4), posterior cerebral artery (n=4), and tandem occlusion (n=22). Successful recanalization (TICI ≥2b or 3) was achieved in 125 patients (91.2%). A good clinical outcome (mRS≤2) was observed in 82 patients (59.9%), while 55 patients (40.0%) achieved excellent clinical outcomes (mRS<2). A total of 12 patients (8.8%) died following IAT. Causes of death included medical complications such as pneumonia, sepsis, myocardial infarction, and gastric cancer (n=6), procedural intracranial hemorrhage (n=2), and severe brain swelling due to infarction progression (n=4).

Table 1 presents a comparison of demographic characteristics, treatment time intervals, and radiological and clinical outcomes between the MT alone and post-IV t-PA MT groups. Patient age did not significantly differ between the MT alone and post-IV t-PA MT groups (median [IQR]: 69 [60.5–77] vs. 69 [60–77.8], p=0.665). There were no significant differences in past medical history, including diabetes mellitus, hypertension, dyslipidemia, atrial fibrillation, and coronary artery disease. The proportion of anterior circulation occlusions was also comparable between the two groups (MT alone: n=68 [82.9%] vs. post-IV t-PA MT: n=45 [81.8%], p=0.867).

Table 1.

A comparison of the baseline characteristics, treatment timeline and radiological & clinical outcome between the MT alone and IV t-PA plus subsequent MT.

The door-to-puncture time was significantly shorter in patients who underwent mechanical thrombectomy (MT) alone (median [IQR], 84.5 [64.3–107] minutes) compared to those who received MT following intravenous tPA administration (132 [91–164] minutes; p<0.001). Intracranial hemorrhage incidence was similar between the MT alone (n=4, 4.9%) and post-IV t-PA MT (n=4, 7.3%) groups (p=0.714). Likewise, symptomatic intracranial hemorrhage rates did not significantly differ (MT alone: n=3 [3.8%] vs. post-IV t-PA MT: n=0, p=0.274). Thrombus migration rates were also comparable (MT alone: n=3 [3.7%] vs. post-IV t-PA MT: n=6 [10.9%], p=0.156).

The successful recanalization rate did not differ significantly between groups (MT alone: n=76 [92.7%] vs. post-IV t-PA MT: n=49 [89.1%], p=0.466). Rates of good clinical outcomes (MT alone: n=48 [58.5%] vs. post-IV t-PA MT: n=34 [61.8%], p=0.701) and excellent clinical outcomes (MT alone: n=35 [42.7%] vs. post-IV t-PA MT: n=20 [36.4%], p=0.460) were not significantly different. The distribution of 3-month mRS scores was also similar (p=0.056; Fig. 2).

Fig. 2.

Distribution of 3-month mRS. MT, mechanical thrombectomy; IV t-PA, intravenous tissue plasminogen activator; mRS, modified Rankin Scale

Table 2 compares patients with good and poor clinical outcomes. Patients with good outcomes were significantly younger (median [IQR]: 69 [58–75] vs. 71 [63.5–80], p=0.027). No significant differences were observed in past medical history or occlusion site between outcome groups. However, initial NIHSS scores were significantly lower in the good outcome group (median [IQR]: 11 [7–15] vs. 15 [11–18], p=0.001). Door-to-puncture time was significantly shorter in the good outcome group (mean±SD: 100±40.6 minutes) than in the poor outcome group (137±121 minutes; p=0.013). Although the rate of successful recanalization was higher in the good outcome group (n=77 [93.9%]) compared to the poor outcome group (n=48 [87.3%]), the difference was not statistically significant (p=0.222).

Table 2.

A comparison of the baseline characteristics, treatment timeline and clinical and radiological outcomes between the good clinical outcome group and the poor clinical outcome group.

In multivariable analysis, both the initial NIHSS score and door-to-puncture time were independently associated with favorable clinical outcomes at 90 days. Specifically, for each 1-point decrease in the NIHSS score on admission, the odds of achieving functional independence (mRS 0–2) increased by approximately 12.7%. Likewise, for every 1-minute reduction in door-to-puncture time, the odds of good outcome increased by approximately 1.3%. Because the initial clinical status is a non-modifiable factor, these findings underscore the clinical importance of minimizing treatment delays in patients undergoing mechanical thrombectomy (Table 3).

Table 3.

Multivariable logistic regression analysis of good clinical outcomes

DISCUSSION

In clinical practice, however, the use of IV t-PA may delay MT due to the need to evaluate patient response and logistical factors such as on-call interventionalist availability. Moreover, IV t-PA may increase the risk of thrombus migration into eloquent or distal vessels, which may be difficult to manage with current MT tools. Unlike conventional bridging therapy, which involves immediate transition to mechanical thrombectomy during or soon after IV t-PA infusion, a delayed approach—administering IV t-PA first and performing MT only after assessing the clinical response—represents a distinct treatment paradigm. Given these limitations, the role of prior IV t-PA plus subsequent MT for large artery occlusion within 4.5 hours warrants re-evaluation.

Door-to-puncture time has emerged as a crucial modifiable determinant of favorable clinical outcomes. The 2015 AHA guidelines recommend initiating MT without waiting to assess the clinical response following IV t-PA administration [8,9]. In our study, the door-to-puncture time was significantly longer in the post-IV t-PA MT group (median [IQR]: 132 minutes [91–164]) compared to the MT alone group (84.5 minutes [64.3–107], p<0.001). This finding suggests that IV t-PA without bridge therapy may inadvertently delay definitive treatment in some real-world settings.

Although current guidelines recommend the administration of intravenous t-PA prior to endovascular therapy when feasible [8,9], our findings suggest that omitting IV t-PA may not compromise procedural success. In fact, the MT-only group demonstrated a slightly higher rate of successful recanalization compared to the post-IV t-PA MT group (92.7% vs. 89.1%), though this difference did not reach statistical significance (p=0.466). This observation raises the possibility that administering IV t-PA first and performing MT only after assessing the clinical response may not confer additional angiographic benefit and could potentially delay definitive reperfusion in certain clinical settings. One possible explanation is the short half-life of t-PA, which may limit its thrombolytic efficacy by the time mechanical thrombectomy is initiated.

Our results indicated that IV t-PA use was not independently associated with good clinical outcomes. Given the short half-life of t-PA (approximately 20 minutes), withholding antiplatelet agents for 24 hours post-thrombolysis may limit its utility, particularly in patients with atherosclerotic stenosis requiring additional intervention. These findings highlight the need to re-evaluate the routine use of IV t-PA prior to mechanical thrombectomy in large artery occlusion, especially when the stroke etiology has not been clearly identified.

Although the proportion of patients achieving good outcomes was slightly higher in the post-IV t-PA MT group (61.8%) than in the MT alone group (58.5%), the difference was not statistically significant (p=0.701). It is worth noting that the MT alone group had a greater proportion of patients with baseline NIHSS scores≥15, which may have contributed to the observed outcome differences.

This study has several limitations. First, it is a retrospective, single-center analysis with a relatively small sample size. Additionally, randomization between treatment groups was not feasible. However, treatment assignment was not intentionally biased. Many patients in the MT alone group were triaged directly for thrombectomy based on prehospital telecommunication between emergency medical technicians and neurointerventionists—a system that, while not mandatory, reduces selection bias.

CONCLUSIONS

In this study, the MT alone group demonstrated a significantly shorter door-to-puncture time compared to the post-IV t-PA MT group, with no statistically significant differences in successful recanalization or clinical outcomes. These findings suggest that mechanical thrombectomy (MT) alone may serve as an effective and timely primary treatment strategy for patients with acute large artery occlusion within 4.5 hours of symptom onset, with outcomes that are not inferior to those achieved with intravenous t-PA followed by MT. These findings suggest that MT without prior IV t-PA may be an effective primary treatment option.

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