This is a retrospective descriptive study. The ASIAN KR is an observational registry of consecutive patients aged 18 or older in whom an endovascular revascularization procedure was attempted for emergent treatment of acute ischemic stroke owing to intracranial and/or extracranial large vessel occlusion. Patient data from three comprehensive stroke centers (Ajou University Hospital [center A, Suwon], Kyungpook National University Hospital [center B, Daegu], and Keimyung University Dongsan Hospital [center C, Daegu]) in South Korea were gathered. Patients who visited centers A and B between January 2011 and February 2016 were included, as were patients who visited center C between January 2011 and May 2016. The database was approved by the Institutional Review Board of each hospital for the registry study. The need for informed consent was waived owing to the retrospective nature of the present study.

All three centers use noncontrast computed tomography (CT) and CT angiography for baseline imaging. Patients who met the criteria for intravenous (IV) recombinant tissue plasminogen activator (rt-PA) within 3 to 4.5 hours of onset were treated with the infusion. If a large artery occlusion corresponding to the stroke signs was observed on CT angiography, the patients were brought to the angiography suite for EVT. Patients in whom large artery occlusions were identified despite IV rt-PA treatment, those who were ineligible to receive IV rt-PA, or patients who were outside the IV rt-PA time window were considered candidates for EVT. If the onset-to-puncture time was expected to be >6 h, the decision to perform EVT was based on multimodal magnetic resonance imaging (MRI), although the protocols are somewhat varied among the three centers. Patients who did not receive EVT owing to spontaneous recanalization were excluded from the registry. The type of EVT procedure was selected at the discretion of the treating interventionist.

For intracranial mechanical thrombectomy, the direct-aspiration method, stent retrieval technique, or a combination of both methods was used. The direct-aspiration method refers to a forced arterial suction technique (FAST) that uses the Penumbra system (Penumbra Inc., Alameda, CA, USA).14 The second-generation direct-aspiration system was defined as the Penumbra MAX system. In the stent retrieval technique, the clot is removed by capturing the thrombus and bringing it out of the body, using stent retrievers such as Solitaire AB/FR (Medtronic, Irvine, CA, USA) or Trevo (Stryker, Kalamazoo, MI, USA).1215 Balloon guide catheters such as Cello (Fuji System Corp., Tokyo, Japan) or Optimo (Tokai Medical Products, Aichi, Japan) were used to prevent clot migration by proximal balloon inflation while performing direct aspiration or stent retrieval.16 Balloon guide catheters were occasionally used for the remote aspiration method by inflating the balloon and aspirating the guide catheter itself.1718 Intracranial or extracranial angioplasty and/or stenting was sometimes performed at the discretion of physicians if necessary.

In each center, clinical data were recorded in a spreadsheet database with center-specif ic patient identif ication numbers. After their identification numbers and names were de-identified, all data were combined. The clinical information included demographics, risk factors, previous antithrombotic and anticoagulant use, premorbid modified Rankin Scale (mRS) scores, and initial National Institute of Health Stroke Scale (NIHSS) scores. Patients' initial vital signs and routine laboratory data were also collected. Additionally, center-reported imaging results that were used for making therapeutic decisions and identifying intra-arterial therapeutic targets, as well as the devices and methods used for EVT, were included. The clinical outcome was defined by the patients' 3-month mRS scores, which were achieved by each center. A good outcome was defined as a 3-month mRS score of 0–2 or a score equal to the prestroke mRS score if the premorbid mRS score was ≥3.

For consistent grading of the multicenter data, core laboratory imaging evaluations were performed. All computed tomography or magnetic resonance imaging data and interventional angiographic data were collected and sent to a core laboratory (Department of Radiology, Ajou University Medical Center, Suwon, South Korea), and then each imaging modality was sent to a designated investigator. After blinding the clinical data and other information, imaging analyses were performed by stroke neurologists, neuroradiologists, and neurointerventionalists with expertise in acute stroke management. The initial large vessel occlusion location was identified on baseline angiography images (S.J.L.). The intracranial occlusion location was classified as internal carotid artery terminus or bifurcation, middle cerebral artery (MCA) M1, MCA M2, or vertebrobasilar artery irrespective of extracranial occlusions. Other or mixed type occlusions were also classified, respectively. The coexistence of relevant extracranial artery involvement was documented separately. By analyzing the angiographic data, intra-arterial treatment targets independent from the initial occlusion sites (Y.H.H.) and the postprocedural reperfusion (modified Treatment In Cerebral Ischemia [mTICI]) grade were identified (Y.H.H. & J.S.L.).19 Successful reperfusion was defined as an mTICI grade of 2b–3.20 The presence of postprocedural hemorrhagic complications was evaluated on brain CT images in most cases or on gradient recalled echo sequence MR images for CT-ineligible cases at around 5 to 7 days after onset. Hemorrhagic transformations were classified according to criteria defined by the European Cooperative Acute Stroke Study (S.I.S.).21 Subarachnoid hemorrhage (SAH) was classified in accordance with the modified Fisher scale (S.I.S.).22 Serious postprocedural hemorrhagic complications were defined as parenchymal hematoma type 2 and/or a modified Fisher grade of 3–4 for SAH. If inconsistencies among the variables were noted, a consensus was reached among the investigators through a full evaluation of all imaging data.

The present analysis first focused on describing the demographics and outcomes of the overall ASIAN KR data. Next, to evaluate which factors contributed to the temporal improvement in clinical outcomes, in patients whose intracranial arterial occlusions were treated by endovascular treatment and whose onset-to-puncture time was <720 min, period-to-period analyses (period 1: January 2011 to July 2014 vs. period 2: August 2014 4 Neurointervention 13, March 2018 Jin Soo Lee, et al. to May 2016) were performed based on the times at which stent retrievers were reimbursed and second-generation direct-aspiration devices became available in Korea. The first generation direct-aspiration systems (Penumbra aspiration catheters) were used in the period 1 whereas the second generation direct-aspiration systems (Penumbra MAX) were used in the period 2. Time metrics, including the onset-to-door, door-to-puncture, and puncture-to-final angiography times, and postprocedural and clinical outcomes were compared between the two periods. Probability of good outcomes was retrieved after adjusting major confounding factors, which included age, sex, premorbid mRS, initial NIHSS score, intracranial occlusion location, infusion of IV rt-PA, onset-to-puncture time, successful reperfusion and serious postprocedural hemorrhagic complications. Regression lines of period 1 and 2, respectively, drawn on scattered plot for the probability of good outcomes and onset-to-puncture time. Additionally, predictors of good outcomes regarding time metrics were determined without period differentiation. Statistical significance was set at P < 0.05. All statistical analyses were performed with SPSS version 22.0 (IBM, Chicago, IL, USA). Graphs were drawn with Excel software (Microsoft, Redmond, WA, USA).

A total of 720 patients (center A: n = 199, center B: n = 348, and center C: n = 173) were included in the entire cohort (Table 1). The 3-month mRS score was missing for one patient. MCA M1 (331 cases [46.0%]) and internal carotid artery terminus (248 cases [34.4%]) occlusions were the major occlusion sites. Overall, intracranial EVT was performed in 702 cases while extracranial EVT was performed in 73 cases. The mean age of the cohort was 67.5 ± 12.3 years, with a median NIHSS score of 16 (interquartile range [IQR]: 12–21). The median onset-to-puncture time was 266 (IQR: 176–450) min, and intravenous tissue plasminogen activator was infused in 374 (51.9%) patients. All patients underwent EVT, and successful reperfusion was achieved in 555 (77.1%) patients. Serious postprocedural hemorrhagic complications were encountered in 72 (10.0%) patients, and a good outcome at 3 months was achieved in 370 (51.5%) patients.

The cohort included patients who were enrolled over a 5-year span. Since 2011, the overall frequency of patients enrolled for emergent EVT continuously increased (Fig. 1A). In terms of the number of total cases treated, the frequency of using the direct-aspiration system remained unchanged (Fig. 1B), while the frequency of stent retriever use continued to increase annually (Fig. 1C). The number of cases in which balloon guide catheters were used increased (Fig. 1D). The percentage of patients with successful reperfusion or complete reperfusion increased annually (Fig. 2A), and the clinical outcomes improved annually (Fig. 2B).

The changes in interventional practices and outcomes were determined by dividing the total study period into two periods among patients who had intracranial large artery occlusions treated by EVT and whose onset-to-puncture time was within 720 min (n = 634) (Table 2). The baseline characteristics such as age, sex, initial NIHSS score, and onset-to-puncture time did not significantly differ between the periods; however, in terms of the time metrics, compared to period 1, the door-to-puncture time was shorter (median 109 [IQR 84–131] vs. 91 [68–116], P < 0.001) while the onset-to-door time was longer (129 [59–241] vs. 143 [64–297], P = 0.057) in period 2. Compared to period 1, successful reperfusion was achieved in a significantly greater percentage of patients in period 2 (74.2% vs. 82.2%, P = 0.019), and the total procedure time from puncture to the final angiography was shorter in period 2 (66 [44–97] vs. 53 [38–81], P < 0.001), as was the door-to-final angiography time (180 [143–226] vs. 155 [123–187], P < 0.001). Moreover, the overall rate of hemorrhagic transformation was reduced (P = 0.010) in period 2, as was the rate of thick SAH (modified Fisher grade 3–4) (5.5% vs. 2.0%, P = 0.034). A good outcome at 3 months was significantly more common in period 2 than it was in period 1 (48.3% vs. 60.2%, P = 0.004). Scattered plot for relationship of onset-to-puncture time and good outcomes showed a different pattern of regression line between period 1 and 2 (Fig. 3). The probability was similarly maintained in both groups until around 400 minutes of onset-to-puncture time; however, after 400 minutes, the probability was steeply reduced in the period 1 whereas the probability was gently reduced in the period 2.

Of the patients who had intracranial large artery occlusions treated by EVT and whose onset-to-puncture time was within 720 min, the in-hospital time metrics, including the door-to-puncture time (0.990 [95% CI, 0.986–0.995], P < 0.001), procedural time (0.983 [95% CI, 0.978–0.988], P < 0.001), and door-to-final angiography time (0.987 [95% CI, 0.984–0.991], P < 0.001), were independent predictors of good outcomes, respectively in separate logistic regression analyses, after adjusting for age, sex, premorbid modified Rankin Scale score, initial NIHSS score, occlusion location, infusion of IV rt-PA, successful reperfusion, and serious hemorrhagic complications; however, the onset-to-door time was not associated with good outcomes (0.999 [95% CI, 0.998–1.000], P = 0.136) (Table 3).