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

BackgroundStroke etiology might influence the clinical outcomes in patients with large vessel occlusion receiving endovascular treatment (EVT) with or without thrombolysis.ObjectiveTo examine whether stroke etiology resulted in different efficacy and safety in patients treated with EVT-alone or EVT preceded by intravenous alteplase (combined therapy).MethodsWe 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.ResultsIn 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).ConclusionsThe 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).

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.

Influence of recent direct-to-EVT trials on practical decision-making for the treatment of acute ischemic stroke patients

Background Current guidelines recommend that eligible acute ischemic stroke (AIS) patients receive intravenous alteplase (IVT) prior to endovascular treatment (EVT). Six randomized controlled trials recently sought to determine the risks of administering IVT prior to EVT, five of which have been published/presented. It is unclear whether and how the results of these trials will change guidelines. With the DEBATE survey, we assessed the influence of the recent trials on physicians’ IVT treatment strategies in the setting of EVT for large vessel occlusion (LVO) stroke. Methods Participants were provided with 15 direct-to-mothership case-scenarios of LVO stroke patients and asked whether they would treat with IVT + EVT or EVT alone, a) before publication/presentation of the direct-to-EVT trials, and b) now (knowing the trial results). Logistic regression clustered by respondent was performed to assess factors influencing the decision to adopt an EVT-alone paradigm after publication/presentation of the trial results. Results 289 participants from 37 countries provided 4335 responses, of which 13.5% (584/4335) changed from an IVT + EVT strategy to EVT alone after knowing the trial results. Very few switched from EVT alone to IVT + EVT (8/4335, 0.18%). Scenarios involving a long thrombus (RR 1.88, 95%CI:1.56–2.26), cerebral micro-hemorrhages (RR 1.78, 95%CI:1.43–2.23), and an expected short time to recanalization (RR 1.46 95%CI:1.19–1.78) had the highest chance of participants switching to an EVT-only strategy. Conclusion In light of the recent direct-to-EVT trials, a sizeable proportion of stroke physicians appears to be rethinking IVT treatment strategies of EVT-eligible mothership patients with AIS due to LVO in specific situations.

A study on relationship of Hounsfield Units value on non-contrast computer tomography and recanalization of intravenous thrombolysis

Objective: To determine whether the administration of intravenous alteplase would be beneficial or futile to patients with acute ischemic stroke caused by large vessel occlusion (LVO) before endovascular treatment (EVT), we conducted this study to determine the relationship between Hounsfield units (HU) in non-contrast computed tomography (NCCT) and recanalization by alteplase. Methods: We performed a retrospective analysis of patients with acute ischemic stroke caused by LVO received intravenous thrombolysis (IVT) or followed by EVT at our center during November 2016 and October 2020. The clinical characteristics and imaging features of patients who achieved recanalization after IVT, and those who did not, were compared. Results: Forty-three eligible patients were enrolled; 12 achieved recanalization by IVT. Baseline clinical characteristics did not differ between patients of the recanalization and non-recanalization groups. HU in the NCCT were estimated and statistically significant maximum and mean values of the ipsilateral middle cerebral artery (MCA) were found between the groups (P< 0.05). The results hint that patients in the non-recanalization group have a higher rHU and δHU value of the ipsilateral MCA compared with recanalization group (P< 0.05). With regards the receiver operator characteristic (ROC) curve, we demonstrated that a high HU value of the ipsilateral MCA could be a predictor for non-recanalization by IVT. Conclusion: Patients suffering LVO stroke are less likely to obtain recanalization by IVT with a high HU value of the ipsilateral MCA. It is feasible to screen patients with LVO using HU for direct EVT.

Radiographic Characteristics of Mild Ischemic Stroke Patients With Visible Intracranial Occlusion: The INTERRSeCT Study

Background and Purpose: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and recanalization rates in these patients. Methods: Among patients enrolled in INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography), a multicenter prospective study of acute ischemic strokes with a visible intracranial occlusion, we compared characteristics of mild (National Institutes of Health Stroke Scale score, ≤5) to moderate/severe strokes. Results: Among 575 patients, 12.9% had a National Institutes of Health Stroke Scale score ≤5 (median age, 70.5 [63–79]; 58% male; median National Institutes of Health Stroke Scale score, 4 [2–4]). Demographics and vascular risk factors were similar between the two groups. As compared with those with a National Institutes of Health Stroke Scale score >5, mild patients had longer symptom onset to assessment times (onset to computed tomography [240 versus 167 minutes] and computed tomography angiography [246 versus 172 minutes]), more distal occlusions (M3, anterior cerebral artery and posterior cerebral artery; 22% versus 6%), higher clot burden score (median, 9 [6–9] versus 6 [4–9]), similar favorable thrombus permeability (residual flow grades I–II, 21% versus 19%), higher collateral flow (9.1 versus 7.6), and lower intravenous alteplase treatment rates (55% versus 85%). Mild patients were more likely to recanalize (revised arterial occlusion scale score 2b/3, 45%; 49% with alteplase) compared with moderate/severe strokes (26%; 29% with alteplase). In an adjusted model for sex, alteplase, residual flow, and time between the two vessel imagings, intravenous alteplase use (odds ratio, 3.80 [95% CI, 1.11–13.00]) and residual flow grade (odds ratio, 8.70 [95% CI, 1.26–60.13]) were associated with successful recanalization among mild patients. Conclusions: Mild strokes with visible intracranial occlusions have different vascular occlusive patterns but similar thrombus permeability compared with moderate/severe strokes. Higher thrombus permeability and alteplase use were associated with successful recanalization, although the majority do not recanalize. Randomized controlled trials are needed to assess the efficacy of new thrombolytics and endovascular therapy in this population.

Abstract 1122‐000179: Very Low Rates of Intracerebral Hemorrhage in Patients Transferred for Mechanical Thrombectomy

Introduction : Background: A common convention among stroke patients being transferred for mechanical thrombectomy, particularly if intravenous thrombolysis has been given, is to undergo a repeat plain brain CT at the treating stroke center. The most concerning among several concerns is the discovery of intracerebral hemorrhage (ICH) which would obviate the value of thrombectomy. This practice has been shown in a previous series to result in a median treatment delay of 20 minutes[1]. By determining the actual incidence of any ICH seen on neuroimaging in patients who undergo repeat imaging on arrival to comprehensive stroke center prior to intervention, we can better determine the true value of this convention of repeat imaging. Methods : Retrospective review of all patients transferred to a single academic comprehensive stroke center for mechanical thrombectomy. We evaluated for the frequency of repeat imaging, the rate of ICH and the rate of undergoing mechanical thrombectomy. Results : There were 682 patients transferred directly for mechanical thrombectomy evaluation over the study period. Intravenous Alteplase was administered to 391 patients prior to arrival and 2 had it on arrival to destination hospital. Plain head CT was repeated at the hub hospital in 590/682 patients (86.5%) (348 with thrombolytics and 242 without. A new intracerebral hemorrhage (ICH) was detected in 9 patients. In only 3 of the 9 patients was mechanical thrombectomy deferred solely due to the ICH (other 6 had no evidence of LVO (4), low ASPECTS (1) or exam improvement (1)). Conclusions : In patients being transferred for mechanical thrombectomy, the rate of ICH on arrival to site hospital was 1.5%. In only one third of those patients (0.5%) was the decision to not proceed with mechanical thrombectomy related to the new ICH. Given the delays in door to puncture times associated with repeat imaging indicated in literature and the low yield in detecting ICH in transfer patients, repeating neuroimaging at comprehensive stroke center obtained for the purpose of ruling out ICH on patients transferred for MT should be reconsidered. Limitations: Our study reflects a single center experience. Other indications for repeat imaging at comprehensive stroke center such as assessment of infarcted core, and presence of large vessel occlusion might still warrant repeat imaging at comprehensive stroke center.

P.190 Choosing Endovascular Treatment or Thrombolysis in Patients with Pre-stroke Comorbidities: UNMASK EVT, a Worldwide Survey

Background: Decisions to treat large-vessel occlusion with endovascular therapy(EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ pre-stroke comorbidities. Methods: In an international survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case-scenarios. Five included comorbidities(metastatic/non-metastatic cancer, cardiac/respiratory/renal disease, non-disabling/mild cognitive impairment[MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. Results: Among 607 physicians(38 countries), EVT was favoured in 1,097/1,379(79.6%) responses for comorbidity-related scenarios under current resources versus 1,510/1,657(91.1%,OR:0.38, 95%CI.0.31-0.47) for six “level-1A” scenarios (assuming ideal conditions:82.7% vs 95.1%,OR:0.25,0.19-0.33). However, this was reversed on including all other scenarios(e.g. under current resources:3,489/4,691[74.4%], OR:1.34,1.17-1.54). Responses favouring alteplase for comorbidity-related(e.g.75.0% under current resources) scenarios were comparable to level-1A scenarios(72.2%) and higher than all others(60.4%). No comorbidity-related factor independently diminished EVT-odds. MCI and dependence carried higher alteplase-odds; cancer and cardiac/respiratory/renal disease had lower odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT, lower alteplase-odds), practicing in East-Asia (higher EVT-odds), and in interventional neuroradiology(lower alteplase-odds vs neurology). Conclusions: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT.

Clinical Outcomes after Intravenous Alteplase in Elderly Patients with Acute Ischaemic Stroke: A Retrospective Analysis of Patients Treated at a Tertiary Neurology Centre in England from 2013 to 2018

Intravenous thrombolysis with alteplase within 4.5 hours from symptom onset is a well-established treatment of acute ischaemic stroke (AIS). The aim was to compare alteplase for AIS between patients aged >80 and ≤80 years in our registry data, from 2013 to 2018. Mechanical thrombectomy cases were excluded. We assessed clinical outcomes over the six-year period and between patients aged over 80 and ≤80 years, using measures including the discharge modified Rankin Scale (mRS), 24-hour National Institutes of Health Stroke Scale (NIHSS) improvement, and symptomatic intracerebral haemorrhage (sICH) rate. Of a total of 805 AIS patients who received intravenous alteplase, 278 (34.5%) were over 80 years old, and 527 (65%) were younger. 616 (76.5%) received thrombolysis ≤ 3 hours after symptom onset and 189 (23.5%) within 3-4.5 hours. Median baseline mRS and NIHSS of the elderly cohort were 1 (IQR 0-5) and 13 (IQR 2-37), respectively, compared to the younger cohort 0 (IQR 0-5) and 9 (IQR 0-29). The sICH rate was 7.2% in the elderly and 4.6% in those ≤80 years, p = 0.05 . NIHSS improved within 24 hours in 34% of the elderly cohort compared to 35% in the younger cohort. At hospital discharge, the mortality rate was 9% in the elderly cohort compared to the 6% in the younger cohort, p = 0.154 . 25% of patients aged >80 years had mRS ≤ 2 compared to 47% in the younger patients ( p < 0.0001 ). In conclusion, thrombolysis in elderly patients results in clinical improvement comparable to younger patients.