Stroke is the second-leading cause of both disability and death worldwide (1). Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) has been one of the primary causes of mortality and morbidity among all stroke patients. Endovascular thrombectomy (EVT) is considered the standard therapy for AIS-LVO in the anterior circulation (2), and its safety and efficacy have been demonstrated in numerous clinical trials (3–8). However, EVT for vessel occlusion caused by intracranial atherosclerotic stenosis (ICAS) is a special concern due to technical difficulty and high requirement of rescue therapy (9).

ICAS is extremely common in Asian countries (1, 10, 11). Although ICAS and cardioembolism (CE) are the two most common etiologies of AIS (11), a difference in outcome of AIS patients due to ICAS and CE after EVT is controversial. One study showed that patients with ICAS were more likely to have favorable outcomes than patients with CE (65% vs. 40.2% p = 0.01) (12), but other studies showed patients with ICAS had less favorable outcomes or no significant difference compared to those with CE (12–20). Thus, the aim of this study is to investigate the clinical characteristics of AIS-LVO patients with ICAS and CE and the impact of stroke etiology (ICAS and CE) on outcomes after EVT.

Among the 443 patients primarily screened in the intervention group, 141 were excluded. The 302 patients included in the present study were divided into the ICAS group (86 patients) and the CE group (216 patients). The details of demographic and baseline characteristics of the patients are shown in Tables 1, 2, respectively.

Among the 86 patients in the ICAS group, 16 were female (18.6%) and the mean age was 62 (±18.0) years. Smoking (52.3% vs. 26.9%, p < 0.001) and drinking (52.3% vs. 23.1%, p < 0.001) was more frequent in the ICAS group, whereas atrial fibrillation (9.3% vs. 39.8%, p < 0.001) and coronary artery disease (8.1% vs. 30.6%, p < 0.001) were more frequent in the CE group. No significant differences existed in biochemical data between the ICAS and CE groups, except TC (4.5 vs. 4.2 mmol/l, p = 0.03), LDL (2.8 vs. 2.6 mmol/l, p = 0.029), and Apo-B (0.9 vs. 0.8 g/l, p = 0.014). Successful recanalization was achieved in 276 patients (91.4%), and no difference existed between the two groups (93.0% vs. 90.7%, p = 0.523). However, rescue therapy was required of 69 patients in the ICAS group (17 were Balloon dilation alone, 40 were Stenting ± balloon dilation, 23 were Intra-arterial medications). 10 patients in the CE group routinely administered intra-arterial medications (tirofiban) by the experienced neurosurgeon because of higher risk of thrombosis after surgery. However, it does not affect the identification of the etiology of AIS.

Univariable analyses and multivariable analysis of functional outcome is shown in Table 3. In the total cohort, 276 patients (91.4%) had successful recanalization, and 145 patients (48.0%) had functional independence at 90 days. The mortality rate of patients was 16.6%. The rate of ICH and sICH was 27.8 and 10.3%, respectively. Successful recanalization was analyzed before and after adjustment (by age, female, CAD, AF, history of smoking, history of drinking, anticoagulation use, NIHSS score, ASPECT score, TC, LDL, OTR, rescue therapy); there was no significant difference observed in the ICAS group vs. the CE group (93.0% vs. 90.7%, OR 1.361, 95%CI 0.527–3.509, p = 0.525; aOR 0.540, 95%CI 0.137–2.128, p = 0.378). Regarding functional outcomes, the ICAS group had similar proportion of favorable outcome (54.7% vs. 45.4%, OR 1.451, 95%CI 0.879–2.398, p = 0.146) and a trend toward lower sICH risk (4.7% vs. 12.5%, OR 0.341, 95%CI 0.116–1.007, p = 0.052) compared to the CE group. There were no significant differences in favorable outcome (aOR 0.722, 95%CI 0.372–1.402, p = 0.336) and sICH (aOR 0.714, 95%CI 0.212–2.404, p = 0.586) after adjustment for confounding factors including age, female, CAD, AF, history of smoking, history of drinking, anticoagulation use, NIHSS score, ASPECT score, TC, LDL, OTR, and successful recanalization. In addition, the rates of mortality and ICH were also not significantly different comparing ICAS and CE before and after adjustment.

In our meta-analysis, the initial search yielded 1,641 studies. A total of 7 eligible previous studies (15, 18, 20, 22–25) were identified meeting the inclusion and exclusion criteria. Of note, studies with vague definitions of other non-ICAS etiologies were eliminated. Our single center data was also included in the meta-analysis. The flow of study selection and details of included studies are shown in Figure 1 and Table 4, respectively.

The results of the meta-analysis of the impact of different etiologies on EVT outcomes are shown in Figure 2. The funnel plot of the meta-analysis is shown in Figure 3. The rate of favorable outcome was slightly higher in the ICAS group compared to the CE group (54.2% vs. 46.3%, OR 1.40, 95%CI 1.00–1.96, I² = 53.2%). Meanwhile, the ICAS group had a lower rate of ICH (19.5% vs. 31.9%, OR 0.60, 95%CI 0.42–0.84, I² = 0.0%) and mortality (14.3% vs. 22.2%, OR 0.63, 95%CI 0.46–0.87, I² = 0.0%) compared to the CE group. There was no significant difference in the sICH rate comparing groups (5.9% vs. 6.7%, OR 0.94, 95%CI 0.55–1.60, I² = 6.3%).

In this study, we investigated the effect of ICAS vs. CE etiology on outcomes after EVT among anterior circulation AIS-LVO patients. There were some differences in demographics comparing ICAS and CE patients, including age, sex, atrial fibrillation, and smoking history. However, even with more frequent rescue therapy and longer time from onset-to-recanalization, patients with ICAS showed comparable rates of favorable functional outcome and mortality compared with those with CE.

The treatment of ICAS-related LVO by EVT is complex and controversial, as immediate re-occlusion often occurs after initial recanalization potentially due to platelet aggregation at the site of the ICAS occlusion. This directly results in an increase in the use of rescue therapy and in the procedural time (13, 26). However, ICAS patients may achieve comparable successful recanalization rates to CE patients, even though ICAS is associated with a higher likelihood of rescue therapy (14, 15, 17, 20, 27). Therefore, prognosis and other outcomes may be affected by different etiologies of AIS.

In our study, some demographic differences existed between patients with ICAS and CE. Patients in the CE group were older and more likely to have atrial fibrillation history than those in the ICAS group, which supports the hypothesis that atrial fibrillation, more prevalent among elderly patients, is the most common mechanism of thrombogenesis (28). This phenomenon has also been observed in previous studies (18, 23, 25, 29). ICAS patients, in the present study, tended to be males and were more likely to have less healthy lifestyles, such as smoking and drinking, and to have comorbidities, such as coronary artery disease. These tendencies have also been observed in previous studies (14, 17, 27). However, other studies have shown no difference in age and sex comparing the two etiologies (13, 14, 17). Additionally, the ICAS group had a lower average NIHSS score and a higher average ASPECTS score than the CE group. This might be explained by an attenuation of clinical severity by pre-established collateral due to in-situ stenosis (ICAS 71% vs. CE 60%, aOR 1.67, 95%CI 1.17–2.39) (22).

Several studies have previously compared the effects of different etiologies on outcomes after EVT, but the data are limited overall, and there are conflicting results. Two studies showed that ICAS patients tended to have lower rates of successful recanalization and less favorable outcomes (13, 16). However, the majority have shown that favorable outcomes and mortality were not significantly different between ICAS and CE etiologies, findings that corroborate our study. In the accompanying systematic review and meta-analysis, we found that ICAS patients were more likely to have favorable outcomes with less mortality and ICH. In contrast, Yoon et al. (12) showed that the ICAS group had more successful recanalization and favorable outcomes compared to the CE group, possibly related to improved collateral circulation due to chronic stenosis in the target vessel (22). The differences observed between etiologies could indicate that the sources of thrombus are potentially related to outcomes. Further large-sample trials should be conducted to investigate this further.

This study has some limitations. The study is limited by its retrospective pattern which has an inherent bias. The sample size of patients was limited due to the use of single-center data. Moreover, this study was performed in an Asian country, with ICAS being more prevalent compared with other counties in Europe and the United States. Therefore, there may be limited generalizability and the results should be examined in further studies. As the results showed no difference in functional outcomes between two etiologies, future research could focus on the etiology diagnosis approach or other influencing factors of outcomes.

Etiology was not considered as an important factor in functional outcome, despite the differences in baseline characteristics and technical EVT approach. The current study of anterior circulation AIS-LVO patients supports that outcomes for those with ICAS are not significantly different from those with CE.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the institutional ethics committee of Xuanwu Hospital, Capital Medical University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

BY designed experiments. CM, WC, YH, YC, YW, JC, PG, FC, QM, and LJ organized clinical database. CM and WC contributed to the selection and data extraction processes of literature in meta-analysis. CM, WC, and YH wrote the manuscript. QT performed the statistical analysis. AD, RR, and WC revised the manuscript. All authors read and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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