Endovascular Therapy for Acute Stroke with a Large Ischemic Region.

BACKGROUND: Endovascular therapy for acute ischemic stroke is generally avoided when the infarction is large, but the effect of endovascular therapy with medical care as compared with medical care alone for large strokes has not been well studied. METHODS: We conducted a multicenter, open-label, randomized clinical trial in Japan involving patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) value of 3 to 5 (on a scale from 0 to 10, with lower values indicating larger infarction). Patients were randomly assigned in a 1:1 ratio to receive endovascular therapy with medical care or medical care alone within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images. Alteplase (0.6 mg per kilogram of body weight) was used when appropriate in both groups. The primary outcome was a modified Rankin scale score of 0 to 3 (on a scale from 0 to 6, with higher scores indicating greater disability) at 90 days. Secondary outcomes included a shift across the range of modified Rankin scale scores toward a better outcome at 90 days and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours. RESULTS: A total of 203 patients underwent randomization; 101 patients were assigned to the endovascular-therapy group and 102 to the medical-care group. Approximately 27% of patients in each group received alteplase. The percentage of patients with a modified Rankin scale score of 0 to 3 at 90 days was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval [CI], 1.35 to 4.37; P = 0.002). The ordinal shift across the range of modified Rankin scale scores generally favored endovascular therapy. An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (relative risk, 3.51; 95% CI, 1.76 to 7.00), and any intracranial hemorrhage occurred in 58.0% and 31.4%, respectively (P<0.001). CONCLUSIONS: In a trial conducted in Japan, patients with large cerebral infarctions had better functional outcomes with endovascular therapy than with medical care alone but had more intracranial hemorrhages. (Funded by Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy; RESCUE-Japan LIMIT ClinicalTrials.gov number, NCT03702413.).

Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials.

BACKGROUND: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. METHODS: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986. FINDINGS: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly. INTERPRETATION: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment. FUNDING: Stryker and Amsterdam University Medical Centers, University of Amsterdam.

High plasma BNP concentration associates with clinical outcome after mechanical thrombectomy: Post hoc analysis of SKIP.

OBJECTIVES: Heart failure may result in reduced brain perfusion, limiting the blood flow needed to achieve clinical recovery. We investigated whether plasma levels of brain natriuretic peptide (BNP), a biological marker of heart failure, were related to clinical outcomes after mechanical thrombectomy (MT). MATERIALS AND METHODS: Data were analyzed from stroke patients with internal carotid or middle cerebral artery occlusion enrolled in the SKIP trial for whom plasma level of BNP was evaluated on admission. Favorable outcome was defined as a modified Rankin scale score of 0-2 at 3 months. RESULTS: Among 169 patients (median age, 74 years; 62% men, median National Institutes of Health Stroke Scale score, 18), 104 (62%) achieved favorable outcomes. Median plasma BNP level was lower in the favorable outcome group (124.1 pg/mL; interquartile range [IQR], 62.1-215.5 pg/mL) than in the unfavorable outcome group (198.0 pg/mL; IQR, 74.8-334.0 pg/mL; p=0.005). In multivariate regression analysis, the adjusted odds ratio for BNP for favorable outcomes was 0.971 (95% confidence interval, 0.993-0.999; p=0.048). At 3 months after onset, the favorable outcome rate was lower in the ≥186 pg/mL group (45%) than in the <186 pg/mL group (72%; p=0.001). This significant difference remained regardless of the presence of atrial fibrillation (AF), with rates of 47% and 76%, respectively, in AF patients (p=0.003) and 33% and 68%, respectively, in patients without AF (p=0.046). CONCLUSION: High plasma BNP concentration appears associated with unfavorable outcomes after MT.

[Vascular Anatomy of the Middle Cerebral Artery and Cerebral Large Vessel Occlusion].

The middle cerebral artery divides into the cortical and perforating branches that supply blood to the extensive cerebral cortex and basal ganglia. In addition to an understanding of the normal vessel diameter and length, endovascular physicians should be familiar with anatomical variations. Understanding the perfusion territory is important for accurate diagnosis of the disease type.

Safety of Apixaban Monotherapy for Non-Valvular Atrial Fibrillation-Related Acute Stroke with Intra-/Extracranial Artery Stenosis.

INTRODUCTION: We investigated whether apixaban is safe for the prevention of further adverse events in non-valvular atrial fibrillation (NVAF) patients with intra-/extracranial artery stenosis (Stenosis group) compared with acute large vessel occlusion without intra-/extracranial artery stenosis (No stenosis group). We also examined whether combination therapy using apixaban and antiplatelet is safe. METHODS: ALVO (Apixaban on clinical outcome of patients with Large Vessel Occlusion [LVO] or stenosis) was a historical and prospective multicenter registry at 38 centers in Japan. Patients with NVAF and acute LVO or stenosis who received apixaban within 14 days after onset were included. We conducted the post hoc analysis using the ALVO dataset. We compared patients with stenosis versus those without stenosis in terms of the primary outcome, which was defined as a composite of all-cause death, major bleeding events, and ischemic events 365 days after onset. RESULTS: Of the 662 patients, 54 (8.2%) patients were classified into the Stenosis group, and 104 patients of the total (16%) reached the primary outcome. The cumulative incidence of primary outcome was not significantly different between the No stenosis and the Stenosis groups (hazard ratio [HR] 1.2, 95% confidence interval [CI]: 0.64-2.4; p = 0.52). Even after adjustment for predictive clinical variates, no significant difference in the primary endpoint between the No stenosis and the Stenosis groups was shown (adjusted HR 1.2, 95% CI: 0.59-2.5; p = 0.60). Fifty patients (7.6%) used an antiplatelet with apixaban. Among the Stenosis group patients, the cumulative incidence of the primary outcome was significantly higher among patients treated with an antiplatelet and apixaban (HR 3.5, 95% CI: 1.0-12; p = 0.048). CONCLUSION: Apixaban monotherapy appears safe for the prevention of further adverse events in the Stenosis group patients similar to the No stenosis group patients. Concomitant use of an antiplatelet might not be favorable in patients with stenosis.

Endovascular Treatment for Anterior Communicating Artery Aneurysms.

Previously, anterior communicating artery aneurysms were considered unsuitable for endovascular treatment. In recent years, however, endovascular treatment has been increasingly performed due to the fact that it is less likely to cause high dysfunction compared to surgery and the treatment has been improved. The International Subarachnoid Aneurysm Trial reported anterior communicating artery aneurysms comprise 45.4% of cerebral aneurysms on which both endovascular treatment and surgery are suitable. The use of the endovascular treatment for anterior communicating artery aneurysms is expected to increase in the future. In this paper, we present cases from our institution based on the characteristics of anterior and distal communicating artery aneurysms, treatment strategies, and treatment indications.

Outcomes of Large Vessel Occlusion Stroke in Patients Aged ≥90 Years.

BACKGROUND AND PURPOSE: Outcomes in patients ≥90 years of age with stroke due to large vessel occlusion were compared between endovascular therapy (EVT) and medical management. METHODS: Of 2420 acute ischemic stroke patients with large vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients aged ≥90 years with occlusion of the internal carotid artery or M1 segment of the middle cerebral artery were included. The primary effectiveness outcome was a favorable outcome at 3 months, defined as achieving a modified Rankin Scale score of 0 to 2 or return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage within 72 hours after onset. Intergroup biases were adjusted by multivariable adjustment with inverse probability of treatment weighting. RESULTS: A total of 150 patients (median age, 92 [interquartile range, 90-94] years; median prestroke modified Rankin Scale score, 2 [interquartile range, 0-4]) were analyzed. EVT was performed in 49 patients (32.7%; mechanical thrombectomy, n=43). The EVT group showed shorter time from onset to hospital arrival (P=0.03), higher Alberta Stroke Program Early CT Score (P<0.01), and a higher rate of treatment with intravenous thrombolysis (P<0.01) than the medical management group. The favorable outcome was seen in 28.6% of the EVT group and 6.9% of the medical management group (P<0.01). EVT was associated with the favorable outcome (adjusted odds ratio, 8.44 [95% CI, 1.88-37.97]). Rates of symptomatic intracranial hemorrhage were similar between the EVT group (0.0%) and the medical management group (3.9%; P=0.30). CONCLUSIONS: Patients who underwent EVT showed better functional outcomes than those with medical management without increased symptomatic intracranial hemorrhages. Given proper patient selection, withholding EVT solely on the basis of the age of patients may not offer the best chance of good outcome. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02419794.

Differences in Acute Ischemic Stroke Management and Prognosis between Multiple Large-Vessel Occlusion and Single Large-Vessel Occlusion: Subanalysis of the RESCUE-Japan Registry 2.

INTRODUCTION: The management and prognosis of acute ischemic stroke due to multiple large-vessel occlusion (LVO) (MLVO) are not well scrutinized. We therefore aimed to elucidate the differences in patient characteristics and prognosis of MLVO and single LVO (SLVO). METHODS: The Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2 (RESCUE-Japan Registry 2) enrolled 2,420 consecutive patients with acute LVO who were admitted within 24 h of onset. We compared patient prognosis between MLVO and SLVO in the favorable outcome, defined as a modified Rankin Scale (mRS) score ≤2, and in mortality at 90 days by adjusting for confounders. Additionally, we stratified MLVO patients into tandem occlusion and different territories, according to the occlusion site information and also examined their characteristics. RESULTS: Among the 2,399 patients registered, 124 (5.2%) had MLVO. Although there was no difference between the 2 groups in terms of hypertension as a risk factor, the mean arterial pressure on admission was significantly higher in MLVO (115 vs. 107 mm Hg, p = 0.004). MLVO in different territories was more likely to be cardioembolic (42.1 vs. 10.4%, p = 0.0002), while MLVO in tandem occlusion was more likely to be atherothrombotic (39.5 vs. 81.3%, p < 0.0001). Among MLVO, tandem occlusion had a significantly longer onset-to-door time than different territories (200 vs. 95 min, p = 0.02); accordingly, the tissue plasminogen activator administration was significantly less in tandem occlusion (22.4 vs. 47.9%, p = 0.003). However, interestingly, the endovascular thrombectomy (EVT) was performed significantly more in tandem occlusion (63.2 vs. 41.7%; adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1-5.0). The type of MLVO was the only and significant factor associated with EVT performance in multivariate analysis. The favorable outcomes were obtained less in MLVO than in SLVO (28.2 vs. 37.1%; aOR, 0.48; 95% CI, 0.30-0.76). The mortality rate was not significantly different between MLVO and SLVO (8.9 vs. 11.1%, p = 0.42). DISCUSSION/CONCLUSION: The prognosis of MLVO was significantly worse than that of SLVO. In different territories, we might be able to consider more aggressive EVT interventions.

Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial.

IMPORTANCE: Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. OBJECTIVE: To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. INTERVENTIONS: Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). MAIN OUTCOMES AND MEASURES: The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. RESULTS: Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78). CONCLUSIONS AND RELEVANCE: Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000021488.

Endovascular Therapy for Acute Ischemic Stroke in Patients with Large-Vessel Occlusion due to Atherosclerotic Stenosis.

OBJECTIVES: Endovascular therapy (EVT) is safe and effective for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). However, the influence of the AIS subtype (large-artery atherosclerosis [LAA] or cardioembolism [CE]) on clinical outcome in patients treated with EVT remains unclear. This study aimed to evaluate the differences in clinical results between the two subtypes using data from a multicenter prospective registry (RESCUE-Japan Registry 2). MATERIALS AND METHODS: Among 2420 patients in RESCUE-Japan Registry, 682 patients who were diagnosed with LAA or CE were enrolled. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 90 days. The secondary outcomes were 90-day mRS 0-1, 0-3, and 6. The relationship between time from onset and clinical outcome was also analyzed. RESULTS: Among the 682 patients, 124 were classified into the LAA group and 558 into the CE group. The baseline National Institutes of Health Stroke Scale score was significantly lower (median 15 vs. 18, p < 0.001). At 90 days, mRS 0-2 was observed in 54 of 124 patients (44%) in the LAA group and 232 of 558 patients (42%) in the CE group (p = 0.69). The proportion of patients with mRS 0-2 tended to decrease according to onset-to-puncture time in the CE group but not in the LAA group (ptrend=0.0007). CONCLUSIONS: The rate of good outcome was similar between LVO due to LAA and CE. However, the rate of favorable outcome did not decrease according to onset-to-puncture time in the LAA group.

Clinical Prediction Rules to Classify Types of Stroke at Prehospital Stage.

Background and Purpose- Endovascular therapy is effective against acute cerebral large vessel occlusion (LVO). However, many patients do not receive such interventions because of the lack of timely identification of the type of stroke. If the types of stroke (any stroke, LVO, intracranial hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) were to be predicted at the prehospital stage, better access to appropriate interventions would be possible. Japan Urgent Stroke Triage (JUST) score was clinical prediction rule to classify suspected patients of acute stroke into different types at the prehospital stage. Methods- We obtained information for signs and symptoms and medical history of consecutive suspected patients of acute stroke at prehospital stage from paramedics and final diagnosis from the receiving hospital. We constructed derivation cohort in the historical multicenter cohort study from June 2015 to March 2016 and validation cohort in the prospective multicenter cohort study from August 2016 to July 2017. The derivation and the validation cohorts included 1229 and 1007 patients, respectively. We constructed multivariate logistic regression models with 21 variables to develop clinical prediction rules, which distinguish between different types of stroke: any stroke, LVO, ICH, and SAH. Results- Among the 1229 patients (median age, 72 years; 55% men) in the derivation cohort, 533 stroke, 104 LVO, 169 ICH, and 57 SAH cases were observed. The developed rules showed that the areas under the receiver operating curves were 0.88 for any stroke, 0.92 for LVO, 0.84 for ICH, and 0.89 for SAH. The validation cohort of 1007 patients (median age, 75 years; 56% men) showed that the areas under the curves of any stroke, LVO, ICH, and SAH were 0.80, 0.85, 0.77, and 0.94, respectively. Conclusions- These clinical prediction rules can help paramedics classify the suspected patients of stroke into any stroke, LVO, ICH, and SAH groups with excellent accuracy.

Impact of atherosclerotic etiology on technical and clinical outcomes of mechanical thrombectomy with a stent retriever: subanalysis of the Japan Trevo Registry.

BACKGROUND: The safety and effectiveness of stent retriever use for patients with acute large vessel occlusion (LVO) due to intracranial atherosclerotic disease (ICAD) is not well established. We investigated the differences in clinical outcomes in patients with and without ICAD. METHODS: We analyzed the Japan Trevo Registry, a nationwide registry which enrolled patients with acute LVO who underwent endovascular therapy (EVT) using the Trevo retriever alone or in combination with an aspiration catheter. We compared the technical and clinical outcomes of EVT between the ICAD and No-ICAD groups. The primary outcome was effective reperfusion and the secondary outcome was modified Rankin scale (mRS) score 0-2 at 90 days. Safety outcomes were worsening of neurologic symptoms within 24 hours, any intracranial hemorrhage within 24 hours, vessel dissection/vessel perforation related to using the Trevo retriever and mortality at 90 days. RESULTS: A total of 835 patients (45 in the ICAD group and 790 in the No-ICAD group) were analyzed. In the ICAD group, more men (68.9% vs 50.8%, P=0.02) and a lower median National Institutes of Health Stroke Scale score at admission (11 vs 18, P<0.0001) were observed. The primary outcome was significantly more common in the No-ICAD group (92.5%) than in the ICAD group (80.0%) (adjusted odds ratio (aOR) 0.21, 95% CI 0.09 to 0.50). The proportion of patients with mRS score 0-2 at 90 days was significantly lower in the ICAD group (44.4% vs 42.4%, aOR 0.49, 95% CI 0.23 to 1.00, P=0.0496). Other secondary and safety outcomes were not significantly different between the two groups. CONCLUSIONS: Patients with LVO with ICAD had a lower rate of effective reperfusion than those with No-ICAD.

Technical and clinical outcomes of thrombectomy in patients with acute medium vessel occlusion and large vessel occlusion; sub-analyses of Japan Trevo registry.

BACKGROUND: Little is known about endovascular therapy (EVT) for patients with medium vessel occlusion (MeVO) and more work is needed to establish its efficacy and to understand hemorrhagic complications. METHODS: We analyzed the Japan Trevo Registry, which enrolled patients with acute stroke who underwent EVT using Trevo Retriever alone or in combination with an aspiration catheter. The primary outcome was effective reperfusion, and the secondary outcome was modified Rankin scale 0-2 at 90 days. Safety outcomes, including intracranial hemorrhage (ICH), were evaluated using a subgroup analyses focused on any ICH. RESULTS: Among 1041 registered patients, 1025 patients were analyzed. 253 patients had MeVOs, and the majority (89.3%) had middle cerebral artery segment 2 (M2). The median National Institutes of Health Stroke Scale scores at admission were 15 and 19 for the MeVO and LVO groups (p < 0.0001). The primary outcome was 88.9% in MeVO vs. 91.8% in LVO group: adjusted odds ratio (aOR) [95% confidence interval (CI)] 0.60 [0.35-1.03], p = 0.07, and the secondary outcome was 43.2% vs. 42.2%, and the aOR [95%CI] was 0.70 [0.48-1.002], p = 0.051. However, the incidence of any ICH was more prominent in MeVO than in LVO group (35.7% vs. 28.8%, aOR [95%CI] 1.54 [1.10-2.15], p = 0.01). In subgroup analyses, the incidences of any ICH in MeVO group were generally higher than those in LVO group. CONCLUSIONS: The effective reperfusion rate did not differ significantly between MeVO and LVO groups. Future development of devices and treatments for MeVO with fewer hemorrhagic complications is desirable.

Systemic THrombolysis Randomization IN Endovascular Stroke Therapy (SHRINE) Collaboration: a patient-level pooled analysis of the SKIP and DEVT Trials.

OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

Characteristics and prognostic impact of unsuccessful recanalization after endovascular therapy for acute ischemic stroke.

BACKGROUND: Endovascular therapy (EVT) has shown high therapeutic efficacy for acute large vessel occlusion (LVO); however, recanalization is unsuccessful in some cases. This study aimed to examine the characteristics and prognostic impact of unsuccessful recanalization after EVT compared with medical treatment alone. METHODS: We conducted a post hoc analysis of RESCUE-Japan Registry 2, a nationwide registry of 2408 consecutive patients with acute LVO. Patients without successful recanalization after EVT (thrombolysis in cerebral infarction grade ≤ 2a) were classified into the Unsuccessful EVT group, and compared with the No-EVT group. To account for selection bias, the outcomes were compared in a propensity score-matched cohort. The outcomes included the modified Rankin Scale (mRS) score at 90 days and intracranial hemorrhage within 72 h after the LVO onset. RESULTS: Among 188 (14.7 %) patients in the Unsuccessful EVT group out of 1281 who underwent EVT, 147 were matched with the No-EVT group, with comparable baseline characteristics. Patients in the Unsuccessful EVT group had a higher distribution of mRS score at 90 days and were less likely to achieve mRS 0-2 compared to those in the No-EVT group (23 % vs. 34 %, OR:0.58, 95 % CI:0.35-0.98). All-cause mortality was higher in the Unsuccessful EVT group (16 % vs. 6.8 %, OR: 2.54, 95 % CIs: 1.16-5.55). Symptomatic intracranial hemorrhage was more frequently observed in the Unsuccessful EVT group (5.4 % vs. 0.7 %, OR: 8.40, 95 % CIs: 1.04-68.1). CONCLUSIONS: The clinical outcomes of patients without successful recanalization after EVT were worse than those who did not undergo EVT.

Optimal Endovascular Therapy Technique for Isolated Intracranial Atherothrombotic Stroke-Related Large-Vessel Occlusion in the Acute-to-Subacute Stage.

BACKGROUND AND PURPOSE: Reocclusion after treatment is a concern in endovascular therapy for isolated intracranial atherothrombotic stroke-related large-vessel occlusion (AT-LVO). However, the optimal endovascular therapy technique for AT-LVO has not yet been investigated. This study evaluated the optimal endovascular therapy technique for AT-LVO in a real-world setting. MATERIALS AND METHODS: We conducted a historical, multicenter registry study at 51 centers that enrolled patients with AT-LVO. We divided the patients into 3 groups based on the endovascular therapy technique: mechanical thrombectomy alone, percutaneous transluminal angioplasty (PTA), and stent deployment. Mechanical thrombectomy alone was classified into the mechanical thrombectomy-only group; PTA and mechanical thrombectomy-PTA, into the PTA group; and mechanical thrombectomy-stent deployment, mechanical thrombectomy-PTA-stent deployment, PTA-stent deployment, and stent deployment-only into the stent group. The primary outcome was incidence of reocclusion of the treated vessels within 90 days of endovascular therapy completion. RESULTS: We enrolled 770 patients and analyzed 509 patients. The rates in the mechanical thrombectomy-only, PTA, and stent deployment groups were 40.7%, 44.4%, and 14.9%, respectively. Incidence rate of residual stenosis >70% of final angiography was significantly higher in the mechanical thrombectomy-only group than in the PTA and stent deployment groups (mechanical thrombectomy-only versus PTA versus stent deployment: 34.5% versus 26.3% versus 13.2%, P = .002). Reocclusion rate was significantly lower in the PTA group than in the mechanical thrombectomy-only group (adjusted hazard ratio, 0.48; 95% CI, 0.29-0.80). Of the patients, 83.5% experienced reocclusion within 10 days after endovascular therapy. Alarmingly, a substantial subset (approximately 62.0%) of patients experienced reocclusion within 2 days of endovascular therapy. Incidence of mRS scores of 0-2 ninety days after endovascular therapy was not significantly different among the 3 groups. Incidences of symptomatic intracranial hemorrhage, any other intracranial hemorrhage, and death were not significantly different. CONCLUSIONS: Incidence rate of reocclusion was significantly lower in the PTA group than in the mechanical thrombectomy-only group. We found no meaningful difference in reocclusion rates between the stent deployment and mechanical thrombectomy-only groups. In Japan, glycoprotein IIb/IIIa inhibitors are not reimbursed. Therefore, PTA might be the preferred choice for AT-LVOs due to the higher reocclusion risk with mechanical thrombectomy-only. Reocclusion was likely to occur within 10 days, particularly within 2 days post-endovascular therapy.

Study protocol of the ASTOP trial: A multicenter, randomized, double-blind, placebo-controlled trial of presurgical aspirin administration for the prevention of thromboembolic complications of coil embolization for ruptured aneurysms.

RATIONALE: Thromboembolism is a serious complication of endovascular treatment for ruptured cerebral aneurysms. The administration of antiplatelet agents before endovascular treatment for ruptured cerebral aneurysms may reduce the risk of thromboembolic complications. AIM: This study aimed to assess the safety and efficacy of preoperative aspirin administration in endovascular treatment for ruptured cerebral aneurysms. SAMPLE SIZE ESTIMATES: Assuming a 15% incidence rate of both intraoperative thromboembolic morbidity and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans assessed by an Independent Review Committee, a sample size of 484 will be required to detect a 10% improvement with aspirin administration with 90% power using the Pearson's chi-square test at a two-sided significance level of 2.5% for each primary outcome, after accounting for a 5% dropout rate. METHODS AND DESIGN: ASTOP is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 484 patients with ruptured cerebral aneurysms receiving coil embolization within 72 h of onset will be randomly assigned 1:1 to receive 200 mg of aspirin or placebo before the procedure. STUDY OUTCOMES: The primary outcomes will be the incidence rates of intraoperative thromboembolic complications and symptomatic ischemic lesions on magnetic resonance imaging diffusion-weighted imaging scans evaluated by the Independent Review Committee. The secondary outcomes will be the incidence rate of cerebral ischemic events and all bleeding events within 14 days of enrollment and functional outcomes defined by the modified Rankin Scale score at 90 days. DISCUSSION: This trial will provide valuable data on the role of antiplatelet agents during endovascular treatment for ruptured cerebral aneurysms. TRIAL REGISTRATION: Registration: Japan Registry of Clinical Trials, Identifier: jRCTs031210421.

Impact of thrombocytopenia on hemorrhagic complications after endovascular therapy for acute large vessel occlusion: Sub-analysis of RESCUE-Japan registry 2.

BACKGROUND: Endovascular treatment (EVT) for patients with large vessel occlusion (LVO) and concurrent thrombocytopenia raises concerns about hemorrhagic complications. We examined the association between thrombocytopenia and clinical outcomes after EVT. METHODS: This is a sub-analysis of the RESCUE-Japan Registry 2, a nationwide registry that enrolled 2420 consecutive acute LVO patients. We evaluated the clinical outcomes in patients who underwent EVT according to their platelet count on admission (Moderate/Severe, < 100 × 109 /L; Mild, 100 to ≤150 × 109/L; Normal, ≥ 150 × 109/L). The outcomes included any and symptomatic intracranial hemorrhage (ICH) after EVT, and modified Rankin Scale (mRS) at 90 days. RESULTS: Of 1268 patients who underwent EVT, the Moderate/Severe and Mild groups consisted of 41 (3.2%), and 193 (15.2%) patients. Any ICH occurred in 37%, 35%, and 24% of Moderate/Severe, Mild, and Normal group patients, respectively, and the adjusted ORs (95% CIs) were 1.50 (0.71-3.18) for Moderate/Severe and 1.87 (1.28-2.73) for Mild, compared to the Normal group (p for trend = 0.004). Symptomatic ICH increased with the severity of thrombocytopenia (9.8% vs 3.6% vs 2.1%), and adjusted ORs were 4.43 (1.16-17.0) in Moderate/Severe and 1.85 (0.71-4.86) in Mild (p for trend = 0.10). Mortality was significantly associated with the severity of thrombocytopenia (p for trend = 0.005), and adjusted ORs were 3.26 (1.29-8.26) in the Moderate/Severe and 2.76 (1.58-4.84) in the Mild groups. CONCLUSIONS: Thrombocytopenia in LVO patients was not rare and associated with the incidence and manifestation of ICH after EVT.

First-in-human trial of a self-expandable, temporary dilation system for intracranial atherosclerotic disease in patients presenting with acute ischemic stroke.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) significantly contributes to ischemic stroke, especially among Asian populations. Large vessel occlusion (LVO) due to underlying ICAD accounts for 15-35% of acute ischemic stroke cases requiring endovascular therapy. However, the successful recanalization rate of ICAD-related LVO remains lower. The TG dilator is a self-expandable device, temporarily dilating ICAD-related blocked blood vessels. OBJECTIVE: To demonstrate TG dilator safety and efficacy for ICAD-related acute ischemic stroke. METHODS: This was a single-arm, open-label, non-randomized, prospective, multicenter, and investigator-initiated trial that involved patients undergoing TG dilator application for acute ischemic stroke caused by ICAD-related LVO or severe stenosis. RESULTS: We enrolled 10 patients in this trial between November 2022 and April 2023. The median (IQR) age was 68 (59.3-75.3) years. Before using the dilator, seven patients received stent retriever treatment. All 10 patients were prescribed a loading dose of aspirin with prasugrel. The median application time was 10 (10-12) min. At the end of the procedure, we achieved significant recanalization immediately in all patients. The stenosis/occlusion decreased from 100% (100-100) to 68% (56.3-75.3). No patient experienced recurrent ischemic stroke or reocclusion within 90 days. We achieved a modified Rankin scale score of 0-2 in 8 patients by day 90. We detected no cases of intracranial hemorrhage, equipment failure, distal embolism, vasospasm, dissection, or perforation requiring intervention. CONCLUSIONS: Acute revascularization using the TG dilator on patients with ICAD-related LVO or severe stenosis did not cause any significant adverse event, and consistently improved blood flow at 90 days.

Efficacy and safety of thrombectomy for acute ischaemic stroke in patients with pre-stroke mRS scores of 2-3: Real-world evaluation from an open-label, prospective, multicentre, observational study.

BACKGROUND: This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2-3 using real-world data. METHODS: Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4-5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0-3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0-3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only. RESULTS: After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2-3). A 90-day mRS score of 0-3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2-3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0-3. CONCLUSION: Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.