Rationale: Intravenous thrombolysis combined with mechanical thrombectomy (MT) has been proven safe and clinical effective in patients with acute ischemic stroke of anterior circulation large vessel occlusion. However, despite reperfusion, a considerable proportion of patients do not recover. Incidence of symptomatic intracerebral hemorrhage was similar between patients treated with the combination of intravenous thrombolysis and MT, as compared to intravenous thrombolysis alone, suggesting that this complication should be attributed to pre-treatment with intravenous thrombolysis. Conversely, intravenous thrombolysis may be beneficial in patients with small clots occluding intracranial arteries with underlying intracranial atherosclerotic disease, not accessible for MT. Aim: To assess whether direct MT is non-inferior compared to combined intravenous thrombolysis plus MT in patients with AIS due to an anterior circulation large vessel occlusion, and to assess treatment effect modification by presence of intracranial atherosclerotic disease. Sample size: Aim to randomize 636 patients 1:1 to receive direct MT (intervention) or combined intravenous thrombolysis plus MT (control). Design: This is a multicenter, prospective, open label parallel group trial with blinded outcome assessment (PROBE design) assessing non-inferiority of direct MT compared to combined intravenous thrombolysis plus MT. Outcomes: The primary outcome is the score on the modified Rankin Scale assessed blindly at 90 (±14) days. An common odds ratio, adjusted for the prognostic factors (age, NIHSS, collateral score), representing the shift on the 6-category mRS scale measured at three months, estimated with ordinal logistic regression, will be the primary effect parameter. Non-inferiority is established if the lower boundary of the 95% confidence interval does not cross 0.8. Discussion: DIRECT-MT could result in improved therapeutic efficiency and cost reduction in treatment of anterior circulation large vessel occlusion stroke.

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.

BACKGROUND AND PURPOSE: There is no consensus on endovascular treatment for terminal ICA. The purpose of this study was to evaluate the comparative safety and efficacy of preferred aspiration thrombectomy and stent retriever thrombectomy for revascularization in patients with isolated terminal ICA occlusion. MATERIALS AND METHODS: We conducted a retrospective analysis of patients with terminal ICA occlusion treated with aspiration thrombectomy or stent retriever thrombectomy in our center, from September 2013 to November 2018. To minimize the case bias, propensity score matching was performed. The primary outcomes were successful reperfusion defined by expanded TICI grades 2b–3 at the end of all endovascular procedures and puncture-to-reperfusion time. RESULTS: A total of 109 consecutive patients with terminal ICA occlusion were divided into the aspiration thrombectomy group (40 patients) and the stent retriever thrombectomy group (69 patients), and 30 patients were included in each group after propensity score matching. The proportion of complete reperfusion was significantly higher in the aspiration thrombectomy group (OR 4.75 [95% CI, 1.10–1.38]; P = .002). The median puncture-to-reperfusion time in the aspiration thrombectomy group was shorter than that in the stent retriever thrombectomy group (38 versus 69 minutes; P = .001). Fewer intracerebral hemorrhage events were recorded in the aspiration thrombectomy group (OR 0.29 [95% CI, 0.09–0.90]; P = .028). No significant differences were observed for good outcomes (OR 1.92 [95% CI, 0.86–4.25]) and mortality (OR 0.84 [95% CI, 0.29–2.44]) at 90 days. CONCLUSIONS: For the treatment of terminal ICA occlusion, aspiration thrombectomy was technically superior to stent retriever thrombectomy in the absence of a balloon guide catheter in achieving successful reperfusion with shorter puncture-to-reperfusion time and procedure-related adverse events.

Background: The added value of intravenous alteplase in reperfusing ischemic brain tissue in patients undergoing endovascular treatment and directly presented to an endovascular treatment-capable hospital is uncertain. We conducted this post hoc analysis of a randomized trial (DIRECT-MT [Direct Intraarterial Thrombectomy in Order to Revascularize Acute Ischemic Stroke Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: A Multicenter Randomized Clinical Trial]) to explore the association of intravenous alteplase, early (preendovascular treatment) reperfusion, and clinical outcome and to determine factors which may modify alteplase treatment effect on early reperfusion. Methods: In this post hoc analysis of the DIRECT-MT randomized trial comparing intravenous alteplase before endovascular treatment versus endovascular treatment only, 623 of 656 randomized patients, with adequate angiographic evaluation for early reperfusion assessment, were included. The association of intravenous alteplase and early reperfusion (defined as expanded Thrombolysis in Cerebral Infarction score ≥2a on angiogram) was assessed using unadjusted comparisons and multivariable logistic regression. Results: Among 623 patients included (317 received intravenous alteplase and 306 did not), early reperfusion occurred in 91 (15%) patients and was associated with better functional outcome (modified Rankin Scale score, 0–2 of 49/91 [54%] versus 178/531 [34%]; adjusted odds ratio, 1.92 [95% CI, 1.15–3.21]; P 33 minutes; adjusted odds ratio, 4.07 [95% CI, 1.86–8.86]; P _interaction =0.012). Conclusions: For patients with large vessel occlusion directly presenting to an endovascular treatment–capable hospital, intravenous alteplase increases early reperfusion when endovascular treatment gets delayed more than approximately half an hour. Thus, intravenous alteplase should be considered if endovascular treatment delays are anticipated by the treating medical team. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03469206.

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 656 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.