Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy : a systematic review and meta-analysis of observational data

Background Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin ScalePeer reviewe

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data

Background: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). Results: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. Conclusion: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty

Endovascular management of acute postprocedural flow diverting stent thrombosis.

INTRODUCTION: Postprocedural thrombosis is a rare complication after flow diverting stent (FD) implantation for aneurysm treatment with few reported cases in the literature. Management strategies and outcomes associated with this complication have not been reported. METHODS: A multicenter retrospective series of cases of acute postprocedural FD thrombosis were compiled and prevalence was calculated based on procedural volumes over a 7 year period. Acute postprocedural FD thrombosis was defined as the development of neurologic deficit with angiographic imaging demonstrating acute thrombus within the index FD stent at least 2 hours following completion of the implantation procedure. RESULTS: A total of 10 cases of postprocedural thrombosis were identified at five participating centers among a total of 768 patients treated (prevalence 1.3%). Thrombosis occurred a median of 5.5 days after implantation (range 0-83 days). 9/10 patients underwent emergent angiography with intent to perform endovascular reperfusion. A variety of different endovascular treatments were used, including aspiration thrombectomy, retrievable stent thrombectomy, balloon angioplasty, and intra-arterial thrombolytic infusion, without any procedural complications. There were no instances of FD migration, stent kinking, or aneurysm rupture. 90% of patients achieved Thrombolysis in Cerebral Infarction 2B or greater revascularization. Favorable clinical outcomes (modified Rankin Scale score of 0-2) at 3 months were achieved in 88% of patients. CONCLUSION: Acute postprocedural thrombosis of an FD is a rare complication that occurs in approximately 1-2% of patients after aneurysm treatment. Patients presenting with acute postprocedural FD thrombosis should be aggressively managed using large vessel occlusion thrombectomy techniques, as good angiographic and clinical outcomes are possible

Impact of COVID-19 on the hospitalization, treatment, and outcomes of intracerebral and subarachnoid hemorrhage in the United States.

ObjectiveTo examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort.MethodsWe performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020-patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes.ResultsThere were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44-0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge.ConclusionsPatients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls

Abstract 169: A Comprehensive Multicenter Evaluation of the Impact of Age on Stroke Thrombectomy Outcomes - Insights From the STAR Collaboration

Introduction: Elderly patients, octogenarians and nonagenarians, were excluded or under-represented in the majority of stroke endovascular thrombectomy (ET) trials. There is conflicting data on the outcomes of ET in the elderly. We evaluated age-dependent outcomes of ET for stroke in a large dataset from the Stroke Thrombectomy and Aneurysm Registry (STAR). Methods: Patients undergoing ET for acute ischemic stroke at 12 comprehensive stroke centers in the US and Europe between 01/2013 and 12/2018 were reviewed. Data was collected retrospectively from patient charts, procedure notes, and patient follow-up in neurology clinics. The primary endpoint was the modified Rankin score (mRS) at 90-days which was dichotomized into good outcome (mRS 0-2) or poor outcome (mRS 3-6). Results: Of 3,850 patients reviewed, 2,827 had 90-day follow-up (mean age 69±14), and were divided into 6 age groups: 20-49 (G1, 10%), 50-59 (G2, 10%), 60-69 (G3, 23%), 70-79 (G4, 27%), 80-89 (G5, 21%), 90 or more (G6, 4%). When adjusted for confounding variables, age was an independent predictor of poor outcome (OR=1.4, p<0.001) and mortality (OR=1.5, p<0.0001). When used as categorical variable, adjusted OR (aOR) for good outcomes were significantly lower in groups G2-G6 compared to G1 (p<0.01, figure), and OR for mortality were significantly higher in G2-G6 compared to G1 (p<0.01, figure). An age increment of 10 years was associated with 23% higher odds of symptomatic hemorrhage, and 50% higher odds of mRS 5-6. The impact of procedure time on good outcome (mRS 0-2) was also age-dependent with aOR=0.84 (p<0.05) in G1,2 compared to aOR=0.65 (p<0.05) in G5,6. Conclusions: Age is a major predictor of functional recovery after ET, and this study demonstrates a clear age-dependent increase in rate of mortality and poor outcomes after ET with exponentially worse outcomes above 80 years of age. Complication rates were not age-dependent. Further studies are required to optimize patient selection for ET in the elderly

Abstract WP3: Predictors and Outcomes of Successful First Pass in Neurothrombectomy- Insights From the STAR Collaboration

Introduction: Shorter procedure time during neurothrombectomy is a strong predictor for good outcomes in stroke patients with large vessel occlusion. We sought to assess the predictors and outcomes of successful first pass (SFP) using multi-center investigator-initiated database. Methods: Prospectively collected neurothrombectomy data from 11 thrombectomy-capable stroke centers was combined in the Stroke Thrombectomy and Aneurysm Registry (STAR). SFP was defined by achieving modified Thrombolysis in Cerebral Infarction (mTICI) score≥2b with a single thrombectomy device pass. We compared the baseline characteristics, procedural metrics, rate of symptomatic intracranial hemorrhage (sICH), and long-term functional outcomes between SFP and non-SFP patients. A multivariate logistic regression analysis was used to assess the predictors of SFP and evaluate whether SFP was an independent predictor for good long-term functional outcomes (90-day mRS≤2). Results: A total of 733 SFP patients and 1134 non-SFP patients were included in this analysis. SFP patients were older (73 vs. 70, P=0.001), had higher Alberta Stroke Program Early CT (ASPECT) score on presentation (9 vs. 8, P=0.002). The use of Solumbra technique was an independent predictor of SFP (OR 1.2, 95% CI 1.1-1.4, P=0.004) after controlling for age, sex, location of occlusion, National Institute of Health stroke scale (NIHSS) on presentation, intravenous alteplase (IV-tPA), and onset to groin (OTG) time. SFP was an independent predictor for good long-term functional outcomes (OR1.6, 95% CI 1.1-2.3, P=0.008) after controlling for age, sex, location of occlusion, NIHSS on presentation, OTG time, IV-tPA, procedure technique, and procedure duration. Conclusion: SFP lead to higher rates of functional independence in stroke patients with large vessel occlusion. These records reiterate the importance of SFP as a benchmark measure for stroke thrombectomy devices

Abstract 148: Mechanical Thrombectomy for Distal Occlusions: Efficacy, Functional and Safety Outcomes. Insights From the STAR Collaboration

Background: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke due to large vessel occlusions. There is strong evidence supporting the benefit of MT in proximal anterior circulation vessel occlusions and basilar occlusions. However, data regarding the efficacy and safety of MT in distal occlusions is scarce. In this study, we aim to report the efficacy, functional and safety outcomes of MT for distal occlusions. Methods: This a retrospective study from 14 comprehensive stroke centers across 4 countries. For the purpose of this study, distal occlusion was defined as MCA occlusion distal to M2 (M3-4 segments), any segments of ACA and any segments of PCA. Patients with concomitant proximal occlusions were excluded from this study. Results: Of 2826 patients, 111 patients were included in this study (mean (SD) age: 69 (13), 51% of patients were female, and 52% received tPA). Median onset to groin time was 241 (IQR, 136 minutes), median NIHSS on admission was 11 (IQR, 8), and median ASPECTS was 10 (IQR, 1). The procedure was done using ADAPT, stent retriever, and Solumbra techniques in 58%, 17% and 15% of patients respectively. Successful revascularization (mTICI 2b-3) and complete revascularization (mTICI 3) were achieved in 78% and 35% of our cohort, respectively. Median procedure time (puncture to revascularization or end of the procedure) was 29 minutes (IQR 42 minutes) and the median number of attempts was 1 (IQR=2). Five percent of patients suffered procedural complications Hemorrhagic complications occurred in 11% of patients of whom only 4% were PH2 hemorrhage. At the last follow up, mRS 0-2 was achieved in 53% of patients. Conclusion: Up to our knowledge, this represents the largest study to the date investigating the safety and efficacy of MT in distal occlusions treatment. MT was safe and achieved a high rate of successful revascularization with an acceptable safety profile

Abstract 150: Multicenter Validation of SPOT, an Artificial Intelligence Based Tool, to Optimize Selection of Elderly Stroke Patients for Mechanical Thrombectomy - Insights From the STAR Collaboration

Introduction: Mechanical thrombectomy for acute ischemic stroke (AIS) is the current standard of care based on level 1 evidence from multiple randomized controlled trials. Recently, real-world indications for mechanical thrombectomy (MT) has extended beyond the inclusion criteria used in the majority of trials including elderly patients. We have recently developed a machine-learning based tool, SPOT, to optimize selection of elderly patients for MT based on single-center data. Here, we use a large cohort of international multicenter patients who underwent MT for AIS to externally validate SPOT. Methods: Patients who underwent MT for AIS at 12 comprehensive stroke centers in the US and Europe between 01/2013 and 12/2018 were reviewed. Patients age 80 years or older were included for validation of SPOT. SPOT is designed based on a combination of decision trees and linear regression models to provide binary output of predicted good (mRS 0-2) or poor outcome (mRS 3-6) after MT. SPOT uses admission variables: age, gender, comorbidities, admission NIHSS, baseline mRS score, ASPECT score and whether IV-tPA was administered. Predicted outcome was compared to actual outcome recorded at 90-days after treatment. A receiver operating characteristic curve was used to evaluate the accuracy of SPOT, and the negative predictive value was computed. The rate of post-procedural hemorrhage and mortality were compared between patients predicted by SPOT to have good versus poor outcome. Results: A total of 3,228 patients underwent MT for AIS during the study duration, of which 647 patients were at least 80 years of age or older and were included in the study. The average age was 85±5 years, and 65% were females. The median mRS score at 90 days was 4, and 21.3% had a good outcome (mRS 0-2). Of patients predicted by SPOT to have a poor outcome, 90% had a poor outcome. The area under the ROC curve was 0.7. The mortality rate in patients predicted by SPOT to have poor outcome had twice higher mortality than those predicted to have good outcome (55% vs 27%, p<0.001). Conclusions: Based on multicenter validation, SPOT presents a clinical decision in aid in assisting for exclusion of elderly patients unlikely to benefit from MT for AIS with a 90% negative predictive value

Abstract WP17: Stent Retriever versus Aspiration Thrombectomy for Distal Occlusions in Acute Stroke - Insights From the STAR Collaboration

Introduction: Aspiration thrombectomy using the ADAPT technique has been shown to have similar efficacy to stent retriever thrombectomy (SRT) in randomized trials of proximal large vessel occlusions. In this work, we investigated the differences in technical and clinical outcomes between ADAPT and SRT for distal vessel occlusions from the Stroke Thrombectomy and Aneurysm Registry (STAR). Methods: Patients undergoing thrombectomy for acute ischemic stroke at 12 comprehensive stroke centers in the US and Europe between 01/2013 and 12/2018 were reviewed. Data was collected retrospectively from patient charts, procedure notes, and patient follow-up in neurology clinics for patients with isolated distal artery occlusion including MCA2, MCA3/4, ACA1/2, and PCA2/3. Clinical endpoint was the modified Rankin score (mRS) at 90-days, and technical outcomes were procedure time, total attempts, and mTICI scores. Results: A total of 464 patients (mean age 69±13.5 years) were treated with ADAPT (56%) or SRT (44%) for distal occlusions during the study period. Patients in the ADPAT group were mainly treated using 3MAX (36%), 4MAX (21%), ACE68/64 (20%), 5MAX/ACE (12%). SRT group included the use of Trevo (50%), Solitaire (44%), or both (5%). There were no significant differences in rates of good outcomes or successful recanalization between ADAPT and SRT groups on multivariate logistic regression analysis controlling for significant confounding variables (p>0.1). Use of SRT in distal occlusions was an independent predictor of longer procedure times compared to ADAPT on linear regression (coefficient=23, p<0.001), and there was a trend toward higher odds of symptomatic hemorrhage in the SRT group (OR=2.6, p=0.06) on multivariate analysis. There were no differences in mortality and complication rates between the two groups. Conclusions: Both SRT and ADAPT thrombectomy lead to comparable rates of favorable outcome for distal vessel occlusion. SRT requires longer procedures and may be associated with higher rates of hemorrhage. Further randomized trials are needed to confirm whether either techniques may provide a better safety or efficacy profile in distal vessel occlusions

Abstract 168: Outcomes of Intra-Arterial Tissue Plasminogen Activator Rescue Therapy During Stroke Thrombectomy-Insights From the STAR Collaboration

Introduction: Intra-arterial tissue plasminogen activator (IA-tPA) can be used as rescue therapy during mechanical thrombectomy for stroke patients, mostly in the setting of distal occlusion. The outcomes of IA-tPA has not been assessed in large-scale multi-center studies yet. Methods: We used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which included prospectively maintained databases of 11 thrombectomy-capable stroke centers in the US, Europe, and Asia. We compared the baseline characteristics, procedural metrics, rate of symptomatic intracranial hemorrhage (sICH), and long-term functional outcomes between thrombectomy patients who received rescue IA-tPA and a control group of thrombectomy patients with matched age, National Institute of Health stroke scale (NIHSS) on presentation, location of occlusion and IV-tPA receipt. Results: A total of 2827 thrombectomy patients were included in the STAR registry. Out of those, 205 patients received IA-tPA. We matched 191 patients from the IA-tPA group with a control group of 191 patients (table 1). No difference was seen in age, sex, race, vascular risk factors, or Alberta Stroke Program Early CT (ASPECT) score between both groups. In addition, procedural metrics, including onset to groin time, the procedure duration, and rate of successful recanalization (modified Thrombolysis in Cerebral Infarction score≥2b) were similar. Finally, similar outcomes were noted in both groups, including the rate of sICH and good 90-day functional outcome (modified Rankin scale≤2). Conclusion: The use of IA-tPA as an adjunctive treatment to mechanical thrombectomy was safe but did not result in a higher rate of successful recanalization or good long-term functional outcomes