Intravenous Thrombolysis Before Endovascular Treatment in Posterior Circulation Occlusions:A MR CLEAN Registry Study

BACKGROUND: The effectiveness of intravenous thrombolysis (IVT) before endovascular treatment (EVT) has been investigated in randomized trials and meta-analyses. These studies mainly concerned anterior circulation occlusions. We aimed to investigate clinical, technical, and safety outcomes of IVT before EVT in posterior circulation occlusions in a nationwide registry. METHODS: Patients were included from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), a nationwide, prospective, multicenter registry of patients with acute ischemic stroke due to a large intracranial vessel occlusion receiving EVT between 2014 and 2019. All patients with a posterior circulation occlusion were included. Primary outcome was a shift toward better functional outcome on the modified Rankin Scale at 90 days. Secondary outcomes were favorable functional outcome (modified Rankin Scale scores, 0–3), occurrence of symptomatic intracranial hemorrhages, successful reperfusion (extended Thrombolysis in Cerebral Ischemia ≥2B), first-attempt successful reperfusion, and mortality at 90 days. Regression analyses with adjustments based on univariable analyses and literature were applied. RESULTS: A total of 248 patients were included, who received either IVT (n=125) or no IVT (n=123) before EVT. Results show no differences in a shift on the modified Rankin Scale (adjusted common odds ratio, 1.04 [95% CI, 0.61–1.76]). Although symptomatic intracranial hemorrhages occurred more often in the IVT group (4.8% versus 2.4%), regression analysis did not show a significant difference (adjusted odds ratio, 1.65 [95% CI, 0.33–8.35]). Successful reperfusion, favorable functional outcome, first-attempt successful reperfusion, and mortality did not differ between patients treated with and without IVT. CONCLUSIONS: We found no significant differences in clinical, technical, and safety outcomes between patients with a large vessel occlusion in the posterior circulation treated with or without IVT before EVT. Our results are in line with the literature on the anterior circulation. GRAPHIC ABSTRACT: A graphic abstract is available for this article.</p

Thrombus Imaging Characteristics to Predict Early Recanalization in Anterior Circulation Large Vessel Occlusion Stroke

The early management of transferred patients with a large vessel occlusion (LVO) stroke could be improved by identifying patients who are likely to recanalize early. We aim to predict early recanalization based on patient clinical and thrombus imaging characteristics. We included 81 transferred anterior-circulation LVO patients with an early recanalization, defined as the resolution of the LVO or the migration to a distal location not reachable with endovascular treatment upon repeated radiological imaging. We compared their clinical and imaging characteristics with all (322) transferred patients with a persistent LVO in the MR CLEAN Registry. We measured distance from carotid terminus to thrombus (DT), thrombus length, density, and perviousness on baseline CT images. We built logistic regression models to predict early recanalization. We validated the predictive ability by computing the median area-under-the-curve (AUC) of the receiver operating characteristics curve for 100 5-fold cross-validations. The administration of intravenous thrombolysis (IVT), longer transfer times, more distal occlusions, and shorter, pervious, less dense thrombi were characteristic of early recanalization. After backward elimination, IVT administration, DT and thrombus density remained in the multivariable model, with an AUC of 0.77 (IQR 0.72–0.83). Baseline thrombus imaging characteristics are valuable in predicting early recanalization and can potentially be used to optimize repeated imaging workflow.</p

Thrombus Imaging Characteristics to Predict Early Recanalization in Anterior Circulation Large Vessel Occlusion Stroke

The early management of transferred patients with a large vessel occlusion (LVO) stroke could be improved by identifying patients who are likely to recanalize early. We aim to predict early recanalization based on patient clinical and thrombus imaging characteristics. We included 81 transferred anterior-circulation LVO patients with an early recanalization, defined as the resolution of the LVO or the migration to a distal location not reachable with endovascular treatment upon repeated radiological imaging. We compared their clinical and imaging characteristics with all (322) transferred patients with a persistent LVO in the MR CLEAN Registry. We measured distance from carotid terminus to thrombus (DT), thrombus length, density, and perviousness on baseline CT images. We built logistic regression models to predict early recanalization. We validated the predictive ability by computing the median area-under-the-curve (AUC) of the receiver operating characteristics curve for 100 5-fold cross-validations. The administration of intravenous thrombolysis (IVT), longer transfer times, more distal occlusions, and shorter, pervious, less dense thrombi were characteristic of early recanalization. After backward elimination, IVT administration, DT and thrombus density remained in the multivariable model, with an AUC of 0.77 (IQR 0.72–0.83). Baseline thrombus imaging characteristics are valuable in predicting early recanalization and can potentially be used to optimize repeated imaging workflow.</p

Effect of First-Pass Reperfusion on Outcome After Endovascular Treatment for Ischemic Stroke

Background First-pass reperfusion (FPR) is associated with favorable outcome after endovascular treatment. It is unknown whether this effect is independent of patient characteristics and whether FPR has better outcomes compared with excellent reperfusion (Expanded Thrombolysis in Cerebral Infarction [eTICI] 2C-3) after multiple-passes reperfusion. We aimed to evaluate the association between FPR and outcome with adjustment for patient, imaging, and treatment characteristics to single out the contribution of FPR. Methods and Results FPR was defined as eTICI 2C-3 after 1 pass. Multivariable regression models were used to investigate characteristics associated with FPR and to investigate the effect of FPR on outcomes. We included 2686 patients of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. Factors associated with FPR were as follows: history of hyperlipidemia (adjusted odds ratio [OR], 1.05; 95% CI, 1.01-1.10), middle cerebral artery versus intracranial carotid artery occlusion (adjusted OR, 1.11; 95% CI, 1.06-1.16), and aspiration versus stent thrombectomy (adjusted OR, 1.07; 95% CI, 1.03-1.11). Interventionist experience increased the likelihood of FPR (adjusted OR, 1.03 per 50 patients previously treated; 95% CI, 1.01-1.06). Adjusted for patient, imaging, and treatment characteristics, FPR remained associated with a better 24-hour National Institutes of Health Stroke Scale (NIHSS) score (-37%; 95% CI, -43% to -31%) and a better modified Rankin Scale (mRS) score at 3 months (adjusted common OR, 2.16; 95% CI, 1.83-2.54) compared with no FPR (multiple-passes reperfusion+no excellent reperfusion), and compared with multiple-passes reperfusion alone (24-hour NIHSS score, (-23%; 95% CI, -31% to -14%), and mRS score (adjusted common OR, 1.45; 95% CI, 1.19-1.78)). Conclusions FPR compared with multiple-passes reperfusion is associated with favorable outcome, independently of patient, imaging, and treatment characteristics. Factors associated with FPR were the experience of the interventionist, history of hyperlipidemia, location of occluded artery, and use of an aspiration device compared with stent thrombectomy

Automated Detection and Location Specification of Large Vessel Occlusion on Computed Tomography Angiography in Acute Ischemic Stroke

Background Fast and accurate detection of large vessel occlusions (LVOs) is crucial in selection of patients with acute ischemic stroke for endovascular treatment. We assessed accuracy of an automated LVO detection algorithm with LVO localization feature. Methods Consecutive patients who underwent computed tomography angiography in 2 centers between January 2018 and September 2019 and between June and November 2020 for suspected anterior circulation LVO were retrospectively included. Reference standard for presence and site of an anterior circulation LVO (intracranial internal carotid artery, M1, or M2 segments of the middle cerebral artery) was established by consensus of 2 independent neuroradiologist readings. All computed tomography angiographies were processed by StrokeViewer‐LVO, Nicolab. Accuracy of this algorithm with LVO localization feature was assessed. Results In total, computed tomography angiographies of 364 patients with suspected anterior circulation LVO were analyzed (mean age 67±15 years; 185 male patients). A total of 180 patients (49%) had an LVO (intracranial internal carotid artery [n=49 (27%)], M1 [n=91 (51%)], and M2 [n=40 (22%)]). Sensitivity and specificity for LVO detection were, respectively, 91% (95% CI, 86%–95%) and 87% (95% CI, 81%–91%). NPV and PPV were, respectively, 91% (95% CI, 86%–94%) and 87% (95% CI, 82%–91%). Accuracy of the LVO localization feature was 95%. Median upload‐to‐notification time was 04:31 (interquartile range, 04:21–05:50) minutes. Conclusions The automated LVO detection algorithm evaluated in this study, rapidly and accurately detected anterior circulation LVOs with high accuracy of the LVO localization feature. Therefore, it is a suitable screening tool to support and speed up diagnosis of stroke

Influence of time metrics on the treatment effect of intravenous alteplase prior to endovascular treatment in MR CLEAN-NO IV

Background: We assessed whether the treatment effect of intravenous alteplase (IVT) prior to endovascular treatment (EVT) on functional outcome is modified by time metrics. Methods: We used data from all patients included in MR CLEAN-NO IV, a randomized trial of IVT followed by EVT versus EVT alone in patients who presented directly to EVT-capable hospitals. The primary outcome was the modified Rankin Scale score at 90 days. We used ordinal regression with a multiplicative interaction term to assess if the effect of IVT is modified by onset-to-randomization (OTR), onset-to-IV-needle (OTN), door-to-groin (DTG) or needle-to-groin (NTG) times. Secondary outcomes included successful reperfusion (extended Thrombolysis In Cerebral Infarction Scale 2b-3) and symptomatic intracranial hemorrhage (sICH). Results: In 539 included patients (266 allocated to IVT+EVT and 273 to EVT alone), median workflow times were OTR: 93 (IQR 71-145) min; OTN: 98 (IQR 75-156) min; DTG: 64 (IQR 51-78) min; and NTG: 28 (IQR 20-41) min. There was a significant association between worse outcomes and longer time intervals for all metrics except NTG. We found no interaction between any of the time metrics and IVT for the effect on functional outcome (p values for interaction: OTR=0.40, OTN=0.39, DTG=0.61, NTG=0.56). We also did not observe any significant interaction for successful reperfusion or sICH. Conclusion: In MR CLEAN-NO IV, the effect of IVT prior to EVT was not modified by OTR, OTN, DTG or NTG times. Our results do not support the use of these metrics to guide IVT treatment decisions prior to EVT in comprehensive stroke centres. Trial registration number: ISRCTN80619088

Aspiration Versus Stent Retriever Thrombectomy for Posterior Circulation Stroke

Background and Purpose: Whereas a clear benefit of endovascular treatment for anterior circulation stroke has been established, randomized trials assessing the posterior circulation have failed to show efficacy. Previous studies in anterior circulation stroke suggest that advanced thrombectomy devices were of great importance in achieving clinical benefit. Little is known about the effect of thrombectomy techniques on outcomes in posterior circulation stroke. In this study, we compare first-line strategy of direct aspiration to stent retriever thrombectomy for posterior circulation stroke. Methods: We analyzed data of patients with a posterior circulation stroke who were included in the Multicentre Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry between March 2014 and December 2018, a prospective, nationwide study, in which data were collected from consecutive patients who underwent endovascular treatment for ischemic stroke in the Netherlands. We compared patients who underwent first-line aspiration versus stent retriever thrombectomy. Primary outcome was functional outcome according to the modified Rankin Scale. Secondary outcomes were reperfusion grade, complication rate, and procedure duration. Associations between thrombectomy technique and outcome measures were estimated with multivariable ordinal logistic regression analyses. Results: Overall, 71 of 205 patients (35%) were treated with aspiration, and 134 (65%) with stent retriever thrombectomy. Patients in the aspiration group had a lower pc-ASPECTS on baseline computed tomography, and general anesthesia was more often applied in this group. First-line aspiration was associated with better functional outcome compared with stent retriever thrombectomy (adjusted common odds ratio for a 1-point improvement on the modified Rankin Scale 1.94 [95% CI, 1.03-3.65]). Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2B) was achieved more often with aspiration (87% versus 73%, P=0.03). Symptomatic hemorrhage rates were comparable (3% versus 4%). Procedure times were shorter in the aspiration group (49 versus 69 minutes P<0.001). Conclusions: In this retrospective nonrandomized cohort study, our findings suggest that first-line aspiration is associated with a shorter procedure time, better reperfusion, and better clinical outcome than stent retriever thrombectomy in patients with ischemic stroke based on large vessel occlusion in the posterior circulation

Timing and causes of death after endovascular thrombectomy in patients with acute ischemic stroke

Introduction: Endovascular thrombectomy (EVT) increases the chance of good functional outcome after ischemic stroke caused by a large vessel occlusion, but the risk of death in the first 90 days is still considerable. We assessed the causes, timing and risk factors of death after EVT to aid future studies aiming to reduce mortality. Patients and methods: We used data from the MR CLEAN Registry, a prospective, multicenter, observational cohort study of patients treated with EVT in the Netherlands between March 2014, and November 2017. We assessed causes and timing of death and risk factors for death in the first 90 days after treatment. Causes and timing of death were determined by reviewing serious adverse event forms, discharge letters, or other written clinical information. Risk factors for death were determined with multivariable logistic regression. Results: Of 3180 patients treated with EVT, 863 (27.1%) died in the first 90 days. The most common causes of death were pneumonia (215 patients, 26.2%), intracranial hemorrhage (142 patients, 17.3%), withdrawal of life-sustaining treatment because of the initial stroke (110 patients, 13.4%) and space-occupying edema (101 patients, 12.3%). In total, 448 patients (52% of all deaths) died in the first week, with intracranial hemorrhage as most frequent cause. The strongest risk factors for death were hyperglycemia and functional dependency before the stroke and severe neurological deficit at 24–48 h after treatment. Discussion and conclusion: When EVT fails to decrease the initial neurological deficit, strategies to prevent complications like pneumonia and intracranial hemorrhage after EVT could improve survival, as these are often the cause of death

Hemorrhage rates in patients with acute ischemic stroke treated with intravenous alteplase and thrombectomy versus thrombectomy alone

Background: Intravenous alteplase treatment (IVT) for acute ischemic stroke carries a risk of intracranial hemorrhage (ICH). However, reperfusion of an occluded vessel itself may contribute to the risk of ICH. We determined whether IVT and reperfusion are associated with ICH or its volume in the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN)-NO IV trial. Methods: The MR CLEAN-NO IV trial randomized patients with acute ischemic stroke due to large vessel occlusion to receive either IVT followed by endovascular treatment (EVT) or EVT alone. ICH was classified according to the Heidelberg bleeding classification on follow-up MRI or CT approximately 8 hours-7 days after stroke. Hemorrhage volume was measured with ITK-snap. Successful reperfusion was defined as extended Thrombolysis In Cerebral Infarction (eTICI) score of 2b-3. Multinomial and binary adjusted logistic regression were used to determine the association of IVT and reperfusion with ICH subtypes. Results: Of 539 included patients, 173 (32%) developed ICH and 30 suffered from symptomatic ICH (sICH) (6%). Of the patients with ICH, 102 had hemorrhagic infarction, 47 had parenchymal hematoma, 44 had SAH, and six had other ICH. Reperfusion was associated with a decreased risk of SAH, and IVT was not associated with SAH (eTICI 2b-3: Adjusted OR 0.45, 95% CI 0.21 to 0.97; EVT without IVT: OR 1.6, 95% CI 0.91 to 2.8). Reperfusion status and IVT were not associated with overall ICH, hemorrhage volume, and sICH (sICH: EVT without IVT, OR 0.96, 95% CI 0.41 to 2.25; eTICI 2b-3, OR 0.49, 95% CI 0.23 to 1.05). Conclusion: Neither IVT administration before EVT nor successful reperfusion after EVT were associated with ICH, hemorrhage volume, and sICH. SAH occurred more often in patients for whom successful reperfusion was not achieved

Association between computed tomography perfusion and the effect of intravenous alteplase prior to endovascular treatment in acute ischemic stroke

Purpose: Intravenous alteplase (IVT) prior to endovascular treatment (EVT) is neither superior nor noninferior to EVT alone in acute ischemic stroke patients. We aim to assess whether the effect of IVT prior to EVT differs according to CT perfusion (CTP)–based imaging parameters. Methods: In this retrospective post hoc analysis, we included patients from the MR CLEAN-NO IV with available CTP data. CTP data were processed using syngo.via (version VB40). We performed multivariable logistic regression to obtain the effect size estimates (adjusted common odds ratio a[c]OR) on 90-day functional outcome (modified Rankin Scale [mRS]) and functional independence (mRS 0-2) for CTP parameters with two-way multiplicative interaction terms between IVT administration and the studied parameters. Results: In 227 patients, median CTP-estimated core volume was 13 (IQR 5–35) mL. The treatment effect of IVT prior to EVT on outcome was not altered by CTP-estimated ischemic core volume, penumbral volume, mismatch ratio, and presence of a target mismatch profile. None of the CTP parameters was significantly associated with functional outcome after adjusting for confounders. Conclusion: In directly admitted patients with limited CTP-estimated ischemic core volumes who presented within 4.5 h after symptom onset, CTP parameters did not statistically significantly alter the treatment effect of IVT prior to EVT. Further studies are needed to confirm these results in patients with larger core volumes and more unfavorable baseline perfusion profiles on CTP imaging