Effect of Time Window on Endovascular Thrombectomy with or without Intravenous Thrombolysis in Acute Ischemic Stroke: Results from DIRECT-MT.

INTRODUCTION: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. METHODS: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h. RESULTS: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. CONCLUSIONS: Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.

Thrombectomy alone vs thrombectomy with over 2/3-dose intravenous thrombolysis pretreatment in the DIRECT-MT trial.

BACKGROUND: The DIRECT-MT trial showed that endovascular thrombectomy (EVT) alone was noninferior to EVT preceded by intravenous alteplase. However, the infusion of intravenous alteplase was uncompleted before the initiation of EVT in most cases of this trial. Therefore, the additional benefit and risk of over 2/3-dose intravenous alteplase pretreatment remain to be assessed. METHODS: We assessed patients with acute anterior circulation ischemic stroke who received EVT alone or with over 2/3-dose intravenous alteplase pretreatment from the DIRECT-MT trial. Patients were assigned to the thrombectomy-alone group and the alteplase pretreatment group. The primary outcome was the distribution of modified Rankin Scale (mRS) at 90 days. The interaction of treatment allocation and collateral capacity was assessed. RESULTS: A total of 393 patients (thrombectomy alone: 315; alteplase pretreatment: 78) were identified. The thrombectomy alone was comparable with alteplase pretreatment prior to the thrombectomy on the distribution of mRS at 90 days without significant effect modification by collateral capacity (adjusted common odds ratio (acOR), 1.12; 95% CI, 0.72-1.74; adjusted P for interaction = 0.83). Successful reperfusion before thrombectomy and the number of passes in the thrombectomy alone group differed significantly from the alteplase pretreatment group (2.6% vs. 11.5%; corrected P = 0.02 and 2 vs. 1; corrected P = 0.003). There was no interaction between treatment allocation and collateral capacity on all outcomes. CONCLUSIONS: EVT alone and EVT preceded by over 2/3-dose intravenous alteplase might have equal efficacy and safety for patients with acute anterior circulation large vessel occlusion, except for successful perfusion before thrombectomy and the number of passes.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT.

BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82-1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62-1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77-1.64) for M1 occlusions, and 1.22 (95% CI, 0.53-2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03469206.

Effect of Clot Burden Score on Safety and Efficacy of Intravenous Alteplase Prior to Mechanical Thrombectomy in Acute Ischemic Stroke: A Subgroup Analysis of a Randomized Phase 3 Trial.

BACKGROUND AND PURPOSE: Whether thrombus burden in acute ischemic stroke modify the effect of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remains uncertain. We aim to investigate the treatment effect of stratified clot burden score (CBS) on the efficacy and safety of direct versus bridging MT. MATERIALS AND METHODS: This is an exploratory subgroup analysis of a randomized trial evaluating the effect of CBS on clinical outcome in the DIRECT-MT trial. CBS was divided into 3 groups (0-3, 4-6, and 7-10) based on preoperative CTA, where higher scores indicated a lower clot burden. We report the adjusted common odds ratio for a shift toward better outcomes on the mRS after thrombectomy alone compared with combination treatment by stratified CBS groups. RESULTS: No modification effect of mRS distribution was observed by CBS subgroups (CBS 0-3: adjusted common ratio odds 1.519 [95% CI, 0.928-2.486]; 4-6: 0.924 [0.635-1.345]; 7-10: 1.040 [0.481-2.247]). Patients with CBS 4-6 had a higher rate of early reperfusion (adjusted OR (aOR), 0.3 [95% CI, 0.1-0.9]), final reperfusion (aOR 0.5 [95% CI, 0.3-0.9]), and fewer thrombectomy attempts (aOR 0.4 [95% CI, 0.1-0.7]). Patients with CBS 7-10 had a higher rate of asymptomatic intracranial hemorrhage (14.9% versus 36.8%, P = .0197) for bridging MT. No significant difference was observed in other safety outcomes by trichotomized CBS. CONCLUSIONS: The subgroup analysis of DIRECT-MT suggested that thrombus burden did not alter the treatment effect of IVT before MT on functional outcomes in CBS subgroups.

Predictors and outcome of early neurological deterioration after endovascular thrombectomy: a secondary analysis of the DIRECT-MT trial.

BACKGROUND: There is uncertainty regarding the predictors of early neurological deterioration (END) after endovascular thrombectomy in patients with acute ischemic stroke (AIS). Limited studies have focused on the effect of END on functional outcome. Our aim was to determine the predictors of END after endovascular thrombectomy in AIS and its effect on functional outcome at 90 days. METHODS: This is a secondary analysis of the DIRECT-MT trial. Patients who failed to complete endovascular thrombectomy were additionally excluded. END was defined as ≥4-point increase in National Institutes of Health Stroke Scale score between admission and 24 hours after endovascular thrombectomy. Multivariable logistic regression was used to identify predictors for END and its effect on the modified Rankin Scale (mRS) score at 90 days. RESULTS: Of 591 patients enrolled, 111 (18.8%) had postoperative END, which was associated with higher ordinal mRS score at 90 days (adjusted common OR (aOR) 6.968, 95% CI 4.444 to 10.926). Non-modifiable factors included baseline Alberta Stroke Program Early CT Score (aOR 0.883, 95% CI 0.790 to 0.987), systolic blood pressure (aOR 1.017, 95% CI 1.006 to 1.028), glucose level (aOR 1.178, 95% CI 1.090 to 1.273), collateral status (aOR 0.238, 95% CI 0.093 to 0.608), occlusion site (aOR 0.496, 95% CI 0.290 to 0.851) and the presence of an anterior communicating artery (aOR 0.323, 95% CI 0.148 to 0.707). Admission-to-groin puncture time (aOR 1.010, 95% CI 1.003 to 1.017), general anesthesia (aOR 2.299, 95% CI 1.193 to 4.444), number of passes (aOR 1.561, 95% CI 1.243 to 1.961) and contrast extravasation (aOR 6.096, 95% CI 1.543 to 24.088) were modifiable predictors for END. CONCLUSIONS: Postoperative END is associated with adverse functional outcome. Several non-modifiable and modifiable factors can predict END and support future treatment decision-making to improve the potential utility of endovascular thrombectomy. TRIAL REGISTRATION NUMBER: DIRECT-MT ClinicalTrials.gov NCT03469206.

Impact of leukoaraiosis in patients with acute ischemic stroke treated with thrombectomy: a post hoc analysis of the DIRECT-MT trial.

BACKGROUND: The influence of leukoaraiosis in patients with acute ischemic stroke (AIS) given intra-arterial treatment (IAT) with or without preceding intravenous thrombolysis (IVT) remains unknown. OBJECTIVE: To assess the clinical and radiological outcomes of IAT in patients with or without leukoaraiosis. METHODS: Patients of the direct mechanical thrombectomy trial (DIRECT-MT) whose leukoaraiosis grade could be assessed were included. DIRECT-MT was a randomized clinical trial performed in China to assess the effect of direct IAT compared with intravenous thrombolysis plus IAT. We employed the Age-Related White Matter Changes Scale for grading leukoaraiosis (ARWMC, 0 indicates no leukoaraiosis, 1-2 indicates mild-to-moderate leukoaraiosis, and 3 indicates severe leukoaraiosis) based on brain CT. The primary outcome was the score on the modified Rankin Scale (mRS) assessed at 90 days. RESULTS: There were 656 patients in the trial, 649 patients who were included, with 432 patients without leukoaraiosis, and 217 (33.4%) patients with leukoaraiosis divided into mild-to-moderate (n=139) and severe groups (n=78). Leukoaraiosis was a predictor of a worse mRS score (adjusted OR (aOR)=0.7 (95% CI 0.5 to 0.8)) and higher mortality (aOR=1.4 (1.1 to 1.9)), but it was not associated with symptomatic intracranial hemorrhage (sICH) (aOR=0.9 (0.5 to 1.5)). IVT preceding IAT did not increase sICH risk for patients with no (aOR=1.4 (0.6 to 3.4)), mild-to-moderate (aOR=1.5 (0.3 to 7.8)), or severe (aOR=1.5 (0.1 to 21.3)) leukoaraiosis. CONCLUSION: Patients with leukoaraiosis with AIS due to large vessel occlusion are at increased risk of a poor functional outcome after IAT but demonstrate similar sICH rates, and IVT preceding IAT does not increase the risk of sICH in Chinese patients with leukoaraiosis.

Intracranial hemorrhage in large vessel occlusion patients receiving endovascular thrombectomy with or without intravenous alteplase: a secondary analysis of the DIRECT-MT trial.

BACKGROUND: Alteplase before thrombectomy for patients with large vessel occlusion stroke raises concerns regarding an increased risk of intracranial hemorrhage (ICH), but the details of this relationship are not well understood. METHODS: This was a secondary analysis of the DIRECT-MT trial. ICH and its subtypes were independently reviewed and classified according to the Heidelberg Bleeding Classification. The effects of alteplase before thrombectomy on ICH and ICH subtypes occurrence were evaluated using logistic regression. Clinical and imaging characteristics that may modify these effects were exploratorily tested. RESULTS: Among 591 patients, any ICH occurred in 254 (43.0%), including hemorrhagic infarction type 1 in 12 (2.1%), hemorrhagic infarction type 2 in 127 (21.7%), parenchymal hematoma type 1 in 34 (5.8%), parenchymal hematoma type 2 in 50 (8.6%), and other hemorrhage types (3a-3c) in 24 (4.1%). Similar ICH frequencies were observed with combined alteplase and thrombectomy versus thrombectomy only (134/292 (45.9%) vs 120/299 (40.1%); OR 1.27, 95% CI 0.91 to 1.75, P=0.16), but patients treated with alteplase had a higher parenchymal hematoma rate (51/287 (17.8%) vs 33/297 (11.1%); OR 1.75, 95% CI 1.08 to 2.85, P=0.024). In the adjusted model, difference in parenchymal hematoma occurrence between groups remained significant (adjusted OR 1.71, 95% CI 1.00 to 2.92, P=0.049). Patients with history of diabetes (Pinteraction=0.048), hypertension (Pinteraction=0.02), antiplatelet therapy (Pinteraction=0.02), anticoagulation therapy (Pinteraction=0.04), and statin administration (Pinteraction=0.02) harbored a higher ICH rate when they received combination therapy. CONCLUSIONS: Our data showed that in the DIRECT-MT trial, alteplase did not increase overall ICH for large vessel occlusion patients treated with thrombectomy, but it increased the parenchymal hematoma rate.

Cost-effectiveness of thrombectomy alone versus alteplase before thrombectomy in acute ischemic stroke: results from the DIRECT-MT.

OBJECTIVE: The use of thrombectomy alone (endovascular thrombectomy [EVT]) was found to be noninferior to combination therapy (EVT plus intravenous thrombolysis [IVT] with alteplase before thrombectomy [EVT+IVT]) in the DIRECT-MT (Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: A Multicenter Randomized Clinical Trial), yet the economic value of omitting alteplase was unclear. Thus, in this paper the authors assessed the cost-effectiveness of EVT alone versus EVT+IVT in the DIRECT-MT. METHODS: In the context of the Chinese healthcare system, the authors conducted a post hoc economic analysis of the DIRECT-MT based on an intention-to-treat approach. Index stroke costs were collected at the individual level, while costs after discharge were complemented with published literature and government websites. Utility weights assessed at 90 days using the 5-Level EQ-5D questionnaire were prospectively collected. For long-term modeled cost-effectiveness analysis, a Markov model with 7 health states corresponding to the 7 modified Rankin Scale scores was used. Deterministic and probabilistic sensitivity analyses were performed. All costs are expressed in 2019 US dollars, discounted using the annual Consumer Price Index in China. RESULTS: During the index hospitalization, the mean medication cost in the EVT-alone group was $487 lower than that in the EVT+IVT group ($2453 [95% CI $2205-$2701] vs $2940 [95% CI $2703-$3178], p = 0.01), but the mean overall costs were similar between the groups ($15,565 [95% CI $14,876-$16,254] vs $15,472 [95% CI $14,714-$16,230], p = 0.73). Within 90 days of the trial, there were no significant differences in total costs (difference -$222 [95% CI -$603 to $161], p = 0.06, bootstrapping) or utility values (median 0.84 [IQR 0.48-0.95] vs median 0.85 [IQR 0.26-1.00]; beta coefficient < 0.01 [95% CI -0.06 to 0.07]) between EVT alone and EVT+IVT. Over the lifetime horizon, EVT alone and EVT+IVT yielded comparable lifetime QALYs (2.02 QALYs [95% CI -0.07 to 4.55 QALYs] vs 1.90 QALYs [95% CI -0.09 to 4.55 QALYs]) and costs ($26,795 [95% CI $15,281-$54,463] vs $27,632 [95% CI $14,558-$52,251]). CONCLUSIONS: In this economic analysis based on a trial conducted in China, the authors found that EVT alone was not associated with economic dominance over EVT+IVT in patients with anterior circulation large-vessel occlusion.

Effect of renal impairment on the efficacy and safety of intra-arterial treatment: A post-hoc analysis of DIRECT-MT study.

OBJECTIVE: To determine the influence of renal impairment on clinical outcomes in patients presenting emergent anterior circulation occlusion treated with mechanical thrombectomy. METHODS: Consecutive patients with anterior circulation stroke treated with mechanical thrombectomy at 41 academic tertiary care centers were included. renal impairment was defined as glomerular filtration rate <60 mL/min/1.73 m2 at the time of admission. The primary outcome was the distribution of scores on the modified Rankin scale, and safety outcomes were mortality within 90 days and hemorrhagic complications. Binary and ordinal logistic regression was used to evaluate the associations between renal impairment and categorical outcomes. Linear regression was used to assess continuous outcomes. RESULTS: A total of 607 patients (47 renal impairment and 600 non-renal impairment) who underwent mechanical thrombectomy were included in this study. Multivariate regression analysis showed that renal impairment was independently associated with the increase of the modified Rankin scale at 90 days. The proportion of patients with successful reperfusion was 71.7% in the renal impairment group and 83.3% in the non-renal impairment group. Renal impairment was an independent predictor of 90-day mortality. No significant treatment for the ordinal modified Rankin scale or 90-day mortality was observed by renal impairment interaction. The risk of asymptomatic intracranial hemorrhage was higher in the mechanical thrombectomy plus IVT group (53.6%) than in the mechanical thrombectomy alone group (15.8%) for renal impairment, but was similar between the mechanical thrombectomy plus IVT group (34.6%) and the mechanical thrombectomy alone group (36.4%) for non-renal impairment (p = 0.01). CONCLUSION: These results demonstrated that the outcomes of mechanical thrombectomy alone and mechanical thrombectomy plus IVT group did not differ significantly in acute stroke patients with and without renal impairment. Also, renal impairment was an independent predictor of worse functional independence and higher mortality at 90 days.

Effect of Admission Hyperglycemia on Safety and Efficacy of Intravenous Alteplase Before Thrombectomy in Ischemic Stroke: Post-hoc Analysis of the DIRECT-MT trial.

Hyperglycemia is associated with decreased recanalization probability and increased risk of hemorrhagic complications for stroke patients treated with intravenous alteplase. However, whether hyperglycemia modifies alteplase treatment effect on clinical outcome in patients with large vessel occlusion stroke undergoing endovascular thrombectomy is uncertain. We conducted this study to determine a possible interaction effect between admission hyperglycemia and intravenous alteplase prior to thrombectomy in patients with large vessel occlusion stroke. In this post-hoc analysis of a randomized trial (DIRECT-MT) comparing intravenous alteplase before endovascular treatment vs. endovascular treatment only, 649 with available baseline glucose measurements were included. The treatment-by-admission hyperglycemia (defined as plasma glucose levels ≥ 7.8 mmol/L [140 mg/dL]) interaction was assessed using logistic regression models. As a result, among 649 patients included, 224 (34.5%) were hyperglycemic at admission. There was evidence of alteplase treatment effect modification by hyperglycemia (Pinteraction = 0.025). In patients without hyperglycemia, combination therapy was associated with better outcomes compared to mechanical thrombectomy alone (adjusted common odd ratio [acOR] 1.46, 95% CI [1.04-2.07]), but not in hyperglycemic patients (acOR 0.74, 95% CI [0.46-1.20]). Combination therapy led to an absolute increase of 6% excellent outcome (mRS 0-1) in non-hyperglycemic patients (aOR 1.71, 95% CI [1.05-2.79]), but resulted in a 12.3% absolute decrease (aOR 0.42 [95% CI, 0.19-0.95] in hyperglycemic patients (Pinteraction = 0.003). In conclusion, for large vessel occlusion patients directly presenting to a thrombectomy-capable hospital, hyperglycemia modified combination treatment effect on clinical outcome. Combination therapy was beneficial in patients without hyperglycemia, while thrombectomy alone may be preferred in hyperglycemic patients. Further studies are needed to confirm this result.Trial Registration Information: clinicaltrials.gov Identifier: NCT03469206.

Effect of stroke etiology on endovascular thrombectomy with or without intravenous alteplase: a subgroup analysis of DIRECT-MT.

BACKGROUND: Stroke etiology might influence the clinical outcomes in patients with large vessel occlusion receiving endovascular treatment (EVT) with or without thrombolysis. OBJECTIVE: To examine whether stroke etiology resulted in different efficacy and safety in patients treated with EVT-alone or EVT preceded by intravenous alteplase (combined therapy). METHODS: We assessed the efficacy and safety of treatment strategy based on prespecified stroke etiology, cardioembolism (CE), large-artery atherosclerosis (LAA), and undetermined cause (UC) for patients enrolled in the DIRECT-MT trial. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Multivariate ordinal logistic regression analysis was used to calculate the adjusted common OR for a shift of better mRS score for EVT-alone versus combined therapy. A term was entered to test for interaction. RESULTS: In this study, 656 patients were grouped into three prespecified stroke etiologic subgroups. The adjusted common ORs for improvement in the 90-day ordinal mRS score with EVT-alone were 1.2 (95% CI 0.8 to 1.8) for CE, 1.6 (95% CI 0.8 to 3.3) for LAA, and 0.8 (95% CI 0.5 to 1.3) for UC. Compared with CE, EVT-alone was more likely to result in an mRS score of 0-1 (pinteraction=0.047) and extended Thrombolysis in Cerebral Infarction ≥2b (pinteraction=0.041) in the LAA group. The differences in mortality and symptomatic intracranial hemorrhage within 90 days were not significant between the subgroups (p＞0.05). CONCLUSIONS: The results did not support the hypothesis that a specific treatment strategy based on stroke etiology should be used for patients with large vessel occlusion (NCT03469206).

Endovascular Treatment of Acute Ischemic Stroke Due to Intracranial Atherosclerotic Large Vessel Occlusion : A Systematic Review.

OBJECTIVE: To evaluate the efficacy and safety of endovascular treatment (ET) of acute ischemic stroke (AIS) caused by intracranial atherosclerotic large vessel occlusion (ICAS-LVO). METHODS: A systemic review and meta-analysis were conducted on studies published between July 2005 and October 2018 on the outcomes of ET in patients with AIS due to ICAS-LVO. The outcomes of the ICAS-LVO and embolic LVO groups were also compared. RESULTS: A total of 17 studies including 1315 subjects with ICAS-LVO were included. In the single-arm meta-analysis, the pooled estimates of successful recanalization rate, favorable outcomes, symptomatic intracranial hemorrhage and mortality were 88% (95% CI (95% confidence interval), 84-92%), 52% (95% CI, 47-56%), 5% (95% CI, 3-7%) and 15% (95% CI, 12-19%) respectively. The preferred primary treatment was stent-retriever thrombectomy (84.1%) and the preferred rescue treatment was stent implantation with or without percutaneous transluminal angioplasty (PTA, 32.7%). In the double-arm meta-analysis, the incidence of symptomatic intracranial hemorrhage was lower in the ICAS-LVO compared to the embolic-LVO group (OR (odds ratio) = 0.60, 95% CI, 0.46-0.77, p < 0.01), whereas the implementation of rescue treatment (OR = 5.94, 95% CI, 3.15-11.19, p < 0.01) and stenting rate (OR = 10.06, 95%CI, 4.43-22.85, p < 0.01) were higher in the ICAS-LVO group. Other parameters were similar in both groups. CONCLUSION: The use of ET is a safe and effective therapeutic option for AIS due to ICAS-LVO. Stent-retriever thrombectomy and stent-implement are the preferred primary and rescue therapies respectively for ICAS-LVO. Less symptomatic intracranial hemorrhage and higher stenting were observed in the ICAS-LVO compared to the embolic-LVO group.

CT Permeability Imaging Predicts Clinical Outcomes in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolytic Therapy.

In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K trans) as a biomarker for blood-brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K trans (K trans-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K trans-PIV, and smaller FIV (P < 0.001). K trans-PIV showed good correlation with FIV (P < 00.001, R 2 = 0.6997). In the regression analyses, K trans-PIV was the best predictor of clinical outcomes (P = 0.009, odds ratio (OR) = 1.960) and also the best predictor for FIV (F = 75.590, P < 0.0001). In conclusion, combining PCT and K trans maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes.