Rate Of Intracranial Hemorrhage Research Articles

Abstract 15692: Clinical Outcomes in TAVR Patients Receiving Oral Anticoagulation Stratified by Baseline Creatinine Clearance Levels: A Subanalysis of the ENVISAGE-TAVI AF Trial

Introduction: The ENVISAGE-TAVI AF (NCT02943785) trial compared edoxaban (EDO) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after successful transcatheter aortic valve replacement (TAVR). The effect of baseline creatinine clearance (CrCl) on efficacy and safety of EDO vs VKA in these patients is not well understood. Hypothesis: The efficacy and safety of EDO vs VKA in patients with AF undergoing TAVR will vary across the range of baseline CrCl. Methods: In this post-hoc analysis from the ENVISAGE-TAVI AF trial, we stratified patients by oral anticoagulation (OAC) strategy (EDO vs VKA) and CrCl (CrCl ≥90 mL/min, CrCl 60-89 mL/min, CrCl 45-59 mL/min, CrCl 30-44 mL/min, CrCl ≤29 mL/min). Results: Of 1426 patients included, 46.3% (n = 676) had CrCl from 60 to 89 mL/min. Patients with lower CrCl trended older in age than those with higher CrCl ( Table 1 ). The annualized event rates for all outcomes tended to increase with decreasing CrCl ( Table 2 ). Across the range of CrCl, patients receiving EDO vs VKA had higher rates of major bleeding and major gastrointestinal bleeding but lower rates of non-cardiovascular death. Major bleeding did not translate into increased all-cause death. Rates of intracranial hemorrhage were higher with EDO vs VKA in patients with CrCl ≥90 mL/min but lower in all other patients. For all-cause death, differences between EDO and VKA were numerical and did not reach statistical significance. Conclusions: In this ENVISAGE-TAVI AF subanalysis, decrements of CrCl appeared to correlate with rates of adverse outcome parameters more than OAC strategy. Due to low event rates in some outcomes, these results should be interpreted with caution.

Abstract 174: Treatment of Unruptured Saccular Aneurysms with PED: A Systematic Review and Meta‐Analysis of Long‐Term Outcomes

Introduction The Pipeline Embolization Device (PED) is commonly used for intracranial aneurysm treatment. While its effectiveness for certain types of aneurysms is well‐established, its efficacy for saccular aneurysms remains debatable. This review and meta‐analysis aimed to assess the long‐term outcomes of PED treatment for unruptured intracranial aneurysms (UIA). Methods A systematic review and meta‐analysis were conducted following PRISMA guidelines. Studies with at least one year of follow‐up after PED treatment for saccular aneurysms were included. The primary endpoint was angiographic complete aneurysm occlusion at long‐term (≥ 12 mo.) follow‐up. Secondary outcomes included long‐term complications. We conducted a meta‐regression analysis to explore the potential sources of heterogeneity across studies. Results Eleven studies on 594 patients with 726 aneurysms were included, of which 5% were previously treated. The mean age was 55.7 years, and 78.3% were women. The mean aneurysm size was 7.72 mm, 8.95% were treated with more than one device, and 2.9% had adjunct coiling. The long‐term complete occlusion rate was 81% (CI 95%: 72% to 88%, p<0.01). Regarding long‐term complications, the rate of symptomatic ischemic stroke was 1% (CI 95%: 0% to 4%, p=0.07), the rate of delayed rupture was 1% (95%, CI 0% to 3%, p=0.02), and the rate of intracranial hemorrhage was 3% (CI 95%: 1% to 6%, p=0.81). The meta‐regression analysis revealed a decreasing trend per year for aneurysmal occlusion, ischemic stroke rate, and aneurysmal rupture rate over time and an increasing trend for ICH over time. Conclusion PED demonstrates high long‐term occlusion and low complication rates, suggesting it is a safe and effective treatment option for unruptured intracranial saccular aneurysms. However, studies with greater than 5‐10 years of follow‐up are needed to evaluate the clinical and radiographical outcomes of incompletely occluded aneurysms Additionally, as newer devices exhibit reduced thrombogenic profiles and ICH rates increase over time, reevaluation of antiplatelet therapy's role, including dosage and DAPT, is warranted.

Abstract 010: Technical Approaches for Intracranial Atherosclerotic Disease Large Vessel Occlusion Strokes

Introduction The optimal management strategy for large vessel occlusion strokes (LVOS) from intracranial atherosclerotic disease (ICAD) remains debated. We aimed to evaluate the efficacy and safety of various acute medical and endovascular management options in patients who underwent mechanical thrombectomy of an ICAD‐related occlusion. Methods Retrospective analysis of ICAD‐related LVOS of a prospective mechanical thrombectomy database at a comprehensive stroke center between November 2010‐May 2023. Endovascular intervention was defined as either angioplasty, stenting, or a combination of both. Acute management was divided into 5 groups: Group#1: proactive antiplatelets (patients who received antiplatelets prior to groin puncture without further endovascular intervention after initial reperfusion); Group#2: reactive antiplatelets (patients who received antiplatelets after groin puncture without further angioplasty and/or stenting after initial reperfusion), Group#3: proactive revascularization (patients treated with angioplasty and/or stenting after initial reperfusion), Group#4: reactive revascularization (patients treated with angioplasty and/or stenting after vessel re‐occlusion after initial reperfusion), and Group #5: rescue revascularization (patients with unsuccessful reperfusion and subsequent angioplasty and/or stenting). Results A total of 200 ICAD‐LVOS MT were identified. Baseline characteristics were comparable between the 5 groups. The rate of TICI2b‐3 final reperfusion was lower in Group 4, while the rate of TICI 2c‐3 final reperfusion was comparable among groups. The rates of in‐hospital re‐occlusion were high even in patients loaded with DAPT before puncture; the rates of re‐occlusion were lower in patients managed with intervention in a proactive manner (Group 3) when compared to those managed in a reactive manner (Group 4) (0% vs 27%, p= 0.005). In ordinal analysis, mRS scores were lowest in Groups 2 and 3.Safety outcomes were comparable with similar rates of symptomatic intracranial hemorrhage (sICH). Conclusion While limited by small subgroup sample size, medical management only was associated with relatively high rates of reocclusion, while proactive angioplasty/stenting with performed best. Symptomatic intracranial hemorrhage was low in medically treated patients. Further studies are warranted.

Efficacy of Urinary Kallidinogenase Plus Intravenous Recombinant Tissue Plasminogen Activator for Stroke Patients With Extended Window: A Retrospective Analysis.

To assess the outcome of human urinary kallidinogenase (HUK) plus recombinant tissue plasminogen activator (rT-PA) intravenous thrombolysis for stroke patients with an extended time window(4.5 to 9 h). A total of 92 acute ischemic stroke patients who fulfilled the criteria were included in this study. All patients received basic treatment and intravenous rT-PA, and 49 patients received additional injections of HUK (HUK group) once a day for 14 consecutive days. Outcomes were indicated by the thrombolysis in cerebral infarction score as the primary endpoint and the National Institute of Health Stroke Scale, modified Rankin Scale, and Barthel Index as the secondary endpoints. The safety outcomes were the rate of symptomatic intracranial hemorrhage, bleeding, angioedema, and mortality. The National Institute of Health Stroke Scale scores were significantly lower in the HUK group at hospital discharge (4.55 ± 3.78 vs 7.88 ± 7.31, P = 0.009) and day 90 (4.04 ± 3.51 vs 8.12 ± 9.53, P = 0.011). The improvements in the Barthel Index scores were more obvious in the HUK group. Patients in the HUK group achieved favorable functional independence (67.35% vs 46.51%; odds ratio: 2.37; 95% CI: 1.01-5.53) at 90 days. The recanalization rate of the HUK group was 64.10%, whereas that was 41.48% in the control group (P = 0.050). The complete reperfusion rates were 42.9% and 23.3% in the HUK group and the control group, respectively. No significant differences were observed for adverse events between the two groups. Combination therapy of HUK plus rT-PA in patients with acute ischemic stroke with an extended time window can safely improve their functional outcomes.

Abstract 014: Beveled‐Tip Aspiration Catheters Reduce Stoke Procedure Time And Cost For Large And Medium Vessel Occlusions

Introduction Thrombectomy catheters with a unique angled‐tip design (ZoomTM Aspiration Catheters, Imperative Care Inc., Campbell, CA) have recently emerged as promising devices for treating acute ischemic stroke. The angled‐tip configuration is engineered to enhance device trackability and optimize clot engagement. Following promising initial results observed during our catheter evaluation, we integrated these novel catheters into the majority of thrombectomy procedures at our institution. In this study, we aimed to determine whether the utilization of angled‐tip catheters could lead to reduced procedural expenses and shorter time to reperfusion in our patient population. Methods We conducted a retrospective single‐center cohort study involving consecutive patients with acute ischemic stroke due to large and medium vessel occlusions. All patients were treated by a single operator between January 2020 and March 2023. Patients treated within the 18‐month period preceding the introduction of the Zoom aspiration catheters using traditional straight‐tip catheters were assigned to the straight‐tip group, while those treated with the Zoom aspiration catheters were assigned to the angled‐tip group. Our primary analysis was a cost comparison between the angled‐tip and straight‐tip groups using the list prices associated with each device employed in the procedures. The secondary analysis was focused on safety and procedural outcomes including self‐adjudicated modified Thrombolysis in Cerebral Infarction (mTICI) reperfusion scores and time from puncture to reperfusion. Frequencies were compared using the Fisher’s exact test and means were compared using a two‐sample t‐test. P‐values <0.05 were considered significant. Results A total of 163 patients were included, with 68 (41.7%) in the straight‐tip group and 95 (58.3%) in the angled‐tip group. There were no significant difference in age, sex, comorbidities, initial National Institutes of Health Stroke Scale score, access site, or procedure type between the two groups. However, utilization of the ADAPT thrombectomy technique was significantly higher in the angled‐tip group (55.9%, 38/68) compared to the straight‐tip group (13.7%, 13/95) which primarily used the Solumbra technique, p<0.001. Overall, the angled‐tip group demonstrated a significant decrease in mean procedure cost ($9,728 vs $12,127; p=0.002). Sub‐group analyses based on the procedure type showed that the angled‐tip group was associated with a numeric decrease in cost; however, due to the lower sample size statistical significance was not achieved (Table). The angled‐tip group was also associated with significantly shorter times to achieve mTICI ≥2B reperfusion (38.30 min vs 53.26 min; p=0.018), mTICI ≥2C reperfusion (45.09 min vs 58.74 min; p=0.042), and procedure completion (46.42 min vs 62.38 min; p=0.022). There were no significant differences in the overall rate of hemorrhage between the angled‐tip (17.9%) and straight‐tip groups (20.6%), p=0.690, though we did observe a numerical decrease in the rate of larger hemorrhages (HI2 and PH2) in the angled‐tip group (Table). Both groups achieve similar rates of mTICI ≥2B reperfusion. Conclusion The angled‐tip catheters were associated with a lower procedure cost and shorter time to achieve reperfusion. Similar rates of reperfusion and intracranial hemorrhages were observed in both groups.

Abstract 234: Antithrombotic use in Emergent Cervical Carotid Artery Stenting in Thrombectomy

Introduction Current literature suggests a benefit in functional outcomes and reperfusion rates when carotid artery stenting (CAS) and mechanical thrombectomy (MT) are performed emergently. However, rates of symptomatic intracranial hemorrhages have been inconclusive. Antithrombotic protocols used in CAS and MT tend to be heterogenous among physicians. There is no standardized data on antithrombotic therapy use during CAS and MT procedures with less associated rates of symptomatic hemorrhagic transformation. We aimed to compare the efficacy and safety of antithrombotic use in patients requiring CAS and MT. Additionally, we sought to analyze clinical and mortality outcomes in CAS and MT retrospectively at our institution. Methods We searched for patients who underwent emergency cervical ICA stent placement and intracranial thrombectomy with stent‐retriever and/or aspiration devices in our institution between 2019‐2023. Clinicoangiographic and antithrombotic data were analyzed. Good clinical outcomes were a < 4 points of NIHSS at 24 hours, mRS (0‐3) at 90 days, and disposition to home or inpatient rehabilitation. Characteristics of hemorrhagic transformation (HT) according to the European Cooperative Acute Stroke Study (ECASS). Clinical, radiographic, and mortality outcomes were described. Results Twenty‐seven patients were treated. The mean age was 64 years, nine females: mean occlusion time 400 minutes, mean fluoro time 32 minutes. Fourteen patients received IV tissue‐type plasminogen (tPA) activator. The admission NIHSS score mean was 16. Stent placement was feasible in all cases. Thrombolysis in Cerebral Infarction score of 2B was achieved in 18 patients (66.7%); the rest had a TICI 3 score. Twelve patients had improved 4 NIHSS points between admission and 24 hours. Dual antiplatelet therapy with aspirin and clopidogrel was used in 15 patients before stenting. While six patients received aspirin and ticagrelor, and the rest received eptifibatide drip. Seven (26%) patients had symptomatic intracranial hemorrhages. Antithrombotic type of treatment had no significant association with bad outcomes (p‐value: 0.872), neither did IV tPA use (p‐value: 0.853). Fourteen patients had good clinical outcomes (mRS 0‐3) at discharge, while eight died. At 90 days follow‐up, the median mRS was 3. Conclusion Our analysis suggests no significant association between symptomatic hemorrhagic transformation with IV tPA or heterogenous antithrombotic use. Our retrospective study has several limitations, including sample size and heterogeneous pathology. Larger studies are needed to stratify symptomatic hemorrhages' high‐risk profile in CAS and MT.

Abstract 073: Thrombectomy Alone Versus Bridging Intravenous Alteplase in A US Population: Regression Discontinuity Analysis

Introduction Recent randomized controlled trials (RCT) failed to demonstrate the non‐inferiority of skipping IV tPA in patients with planned endovascular therapy (EVT). None of these studies included patients from the US due to regulatory challenges. Given that practice patterns vary relative to Asia, Australia, and Europe, we sought to address this topic using a validated alternative to RCTs, regression discontinuity (RD). Methods From the prospectively collected SVIN Registry encompassing all consecutive patients treated with EVT from 12 centers across the US, we identified patients from 12/2010 – 12/2021. RD design achieves quasi‐randomization and can determine causal effects by analyzing subjects on immediately adjacent sides of a cutoff. Here, we take advantage of the sharp drop in the likelihood of IV tPA treatment at the 4.5‐hour mark from the patients’ last known well time. Subjects immediately on either side of the cutoff have markedly different probabilities of receiving the treatment while sharing similar characteristics in other relevant aspects. Patients were excluded if they underwent EVT after inter‐hospital transfer, were inpatient at the time of acute ischemic stroke (AIS), received IV tPA outside the 4.5‐hour window, or were treated with EVT after the 10‐hour window, as these patients would not contribute to the RD analysis. The primary outcome was a good functional outcome defined as 90‐day mRS 0‐2 and was analyzed using validated RD analysis methods with local linear regressions and triangular kernel weights. Secondary endpoints included rates of symptomatic intracranial hemorrhage and substantial reperfusion. Results Among 961 patients who met inclusion criteria, all 12 EVT centers within the SVIN Registry were represented. The median age was 70 [IQR 58‐79], 48% were female, NIHSS was 17, and the most common occlusion location was M1 MCA (45%). There were no substantial differences in presentation characteristics between patients treated with IV tPA and without. We observed a significant fall (30%) in the probability of tPA around the cutoff time of 235 minutes from the last known well to hospital arrival (allowing 35 minutes for in‐hospital evaluation from the 4.5‐hour cutoff), while there were no significant differences in other relevant features including age, NIHSS, ASPECTS, and final reperfusion grade at the cutoff, validating the underlying RD assumptions (Figure A). In RD analysis, we observed no association between IV tPA treatment and functional independence at 90‐days in patients undergoing EVT (risk difference ‐0.29 (95% CI [‐2.75 to 2.15]) (Figure B), nor in the secondary outcomes of excellent outcomes (mRS 0‐1) at 90 days, mortality, symptomatic ICH or first pass reperfusion. Conclusion Here, we perform what we believe to be the strongest study to date examining the benefit of IV tPA in patients undergoing EVT for LVO AIS in a US‐based cohort, and we find no evidence of association with 90‐day functional independence, consistent with findings of RCTs performed outside the US.

Abstract 044: Single‐Step Intracranial Angioplasty followed by Atlas Stent Deployment Through Mini Trek Rx Balloon

Introduction The current FDA approved intracranial stent delivery system requires a multi‐step deployment involving the use of exchange length microwire (ELW), typically 0.014‐inch 300 cm wire, to navigate the balloon catheter, which is then exchanged, after performing the angioplasty, over the ELW to a 0.017’ microcatheter that is used to deploy the intracranial stent. Herein, we describe a single‐step approach to deploy Neuroform Atlas stent (Stryker Neurovascular, Fremont, CA) which is a hybrid laser‐cut, nitinol self‐expanding stent without the need for ELW or lesion re‐access using MINI TREK RX (Abbott Vascular, Inc., Santa Clara, CA, USA) semi compliant balloon adapted from cardiovascular literature which showed a pre‐dilation angioplasty capability in coronary stenotic lesions. Methods We performed a retrospective review of prospectively maintained mechanical thrombectomy (MT) databases of 2 comprehensive stroke centers between November 2020, and May 2023. The inclusion criteria were consecutive large vessel occlusion stroke patients in whom single step MINI TREK RX balloon angioplasty followed by Neuroform Atlas intracranial stent deployment was performed without using ELW (Figure‐1). There was no restriction on time from last known well (TLKW) to MT. During the standard mechanical thrombectomy procedure, intracranial atherosclerotic disease/ significant stenotic lesion was suspected by immediate re‐occlusion/ persistent occlusion following at least 1 thrombectomy pass. This is followed by pursuing intracranial angioplasty and stent placement as a rescue recanalization measure. The primary outcome was successful reperfusion defined as a Modified Treatment in Cerebral Ischemia (mTICI) score of 2b or greater at the end of the procedure. Secondary outcomes included NIH Stroke Scale (NIHSS) at 24 hours, NIHSS at discharge, median modified Rankin Scale (mRS) score at discharge and at 90‐day follow‐up. Safety measures included rates of symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Results Among 9 patients who met our criteria, the median age was 63 (51‐69.5) years and 55.6% were females. Most patients had left middle cerebral artery‐ M1 occlusion (66.7%) and one third received thrombolytics (33.3%). All patients underwent the single‐step approach and achieved successful reperfusion (m TICI 2b‐3) with 2 median number of passes. The median NIHSS was reduced from 13.5 (8.5‐17.5) at baseline to 4 (1‐16.5) at discharge. In addition, median mRS was 1 (1‐3.5) at discharge and 3 (3‐4) at 90 days. None of the patients included in this series had sICH while only one patient with basilar artery occlusion underwent ventriculostomy during hospital stay and was sedated/intubated and died. Conclusion This preliminary experience showed technical feasibility and success of using single‐ step to deploy Neuroform Atlas stent after performing angioplasty using MINI TREK RX without the need for ELW or lesion re‐access. Prospective studies with larger sample size and long‐term clinical follow‐up are warranted to confirm these results.

Abstract 040: Hemorrhagic Conversion Patterns After Transition of Stroke Thrombolysis from Alteplase to Tenecteplase; Real‐World Experience

Introduction Importance:Tenecteplase (TNK) use is more prevalent as the thrombolytic drug of choice for acute ischemic stroke (AIS), given its ease of use with results from randomized trials showing non‐ inferiority and comparable safety to Alteplase (tPA). However, there is conflicting data in terms of intracranial hemorrhage risk. Objective: We are reporting the rate of symptomatic intracranial hemorrhage(sICH) in TNK and tPA treated stroke populations across two large hospital systems. Methods Design: Retrospective cohort observational study. Data was collected from April 1, 2022 through March 29, 2023. Setting: Data was collected from 15 stroke centers: 10 primary and 5 comprehensive stroke centers in Texas. Participants: Inclusion criteria: 18 years or older, suspected to have an AIS were eligible to receive thrombolytic therapy, and received either IV TNK or tPA at the standard dose. A total of 431 patients were included. 216 patients received alteplase and 215 patients received tenecteplase. Exposure: Data was collected 90 days before and 90 days after the stroke center changed from tPA to TNK. Main Outcomes: The primary endpoint was to compare the incidence of sICH according to SITS‐MOST/ECASS‐3 criteria in the tPA and TNK groups. Secondary endpoints included the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBc). Results A total of 431 patients; half of them had been administered Alteplase (n=216) and the other half had Tenecteplase (n=215). Approximately half of them were females 110 (51%) for alteplase and 117 (54%) for Tenecteplase. Almost 2/3 of the study population never smoked; 66% for alteplase 64% for Tenecteplase. Majority of the patient population got thrombolytic therapy within 3 hours 174 (81%) for alteplase versus 176 (82%) for Tenecteplase. 34 patients (15%) in the alteplase group as compared to 26 patients (12%) in the Tenecteplase group had endovascular thrombectomy attempted. 7 patients in the tPA group (3.2%) and 14 patients (6.5%) in the TNK group had sICH. An increase in the NIHSS on arrival (p=0.048) was a statistically significant predictor of sICH. A two sample proportion test on TNK produced a statistically significant increase in Heidelberg Bleed class 3 (HBc3) (p=0.040) over tPA. Conclusion We observed increased cases of bleeding associated with TNK administration with statistically significant increase in the HBc3 when compared to patients who received tPA. Suggested mechanisms of bleeding are hemorrhagic conversion in clinically silent infarcts, and contusions underlying the lesions. These findings suggest a potential need to reevaluate the criteria for administering TNK to patients. Larger studies are required to confirm this data.

Safety and efficacy of the pipeline embolization device for treatment of small vs. large aneurysms: a systematic review and meta-analysis.

Flow diversion with the pipeline embolization device (PED) is increasingly used to treat intracranial aneurysms with high obliteration rates and low morbidity. However, long-term (≥ 1year) angiographic and clinical outcomes still require further investigation. The aim of this study was to compare the occlusion and complication rates for small (< 10mm) versus large (10-25mm) aneurysms at long-term following treatment with PED. A systematic review and meta-analysis were performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We conducted a comprehensive search of English language databases including Ovid MEDLINE and Epub Ahead of Print, In-Process, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Our studies included a minimum of 10 patients treated with PED for small vs. large aneurysms and with at least 12months of follow-up. The primary safety endpoint was the rate of clinical complications measured by the occurrence of symptomatic stroke (confirmed clinically and radiographically), intracranial hemorrhage, or aneurysmal rupture. The primary efficacy endpoint was the complete aneurysm occlusion rate. Our analysis included 19 studies with 1277 patients and 1493 aneurysms. Of those, 1378 aneurysms met our inclusion criteria. The mean age was 53.9years, and most aneurysms were small (89.75%; N = 1340) in women (79.1%; N = 1010). The long-term occlusion rate was 73% (95%, CI 65 to 80%) in small compared to 84% (95%, CI 76 to 90%) in large aneurysms (p < 0.01). The symptomatic thromboembolic complication rate was 5% (95%, CI 3 to 9%) in small compared to 7% (95%, CI 4 to 13%) in large aneurysms (p = 0.01). The rupture rate was 2% vs. 4% (p = 0.92), and the rate of intracranial hemorrhage was 2% vs. 4% (p = 0.96) for small vs. large aneurysms, respectively; however, these differences were not statistically significant. The long-term occlusion rate after PED treatment is higher in large vs. small aneurysms. Symptomatic thromboembolic rates with stroke are also higher in large vs. small aneurysms. The difference in the rates of aneurysm rupture and intracranial hemorrhage was insignificant. Although the PED seems a safe and effective treatment for small and large aneurysms, further studies are required to clarify how occlusion rate and morbidity are affected by aneurysm size.

Low dose intravenous cangrelor versus glycoprotein IIb/IIIa inhibitors in endovascular treatment of tandem lesions

ObjectivesIntravenous (IV) periprocedural antiplatelet therapy (APT) for patients undergoing acute carotid stenting during mechanical thrombectomy (MT) is not fully investigated. We aimed to compare the safety profile of IV low dose cangrelor versus IV glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors in patients with acute tandem lesions (TLs). Materials and methodsWe retrospectively identified all cases of periprocedural administration of IV cangrelor or GP-IIb/IIIa inhibitors during acute TLs intervention from a multicenter collaboration. Patients were divided in two groups according to the IV APT regimen at the time of MT procedure: 1) cangrelor and 2) GP-IIb/IIIa inhibitors (tirofiban and eptifibatide). Safety outcomes included rates of symptomatic intracranial hemorrhage (sICH), parenchymal hematoma type 1 and 2 (PH1-PH2), and hemorrhagic infarction type 1 and 2 (HI1-HI2). ResultsSixty-three patients received IV APT during MT, 30 were in the cangrelor group, and 33 were in the GP-IIb/IIIa inhibitors group. There were no significant differences in the rates of sICH (3.3% vs. 12.1%, aOR=0.21, 95%CI 0.02–2.18, p=0.229), HI1-HI2 (21.4% vs 42.4%, aOR=0.21, 95%CI 0.02–2.18, p=0.229), and PH1-PH2 (17.9% vs. 12.1%, aOR=1.63, 95%CI 0.29–9.83, p=0.577) between both treatment groups. However, there was a trend toward reduced hemorrhage rates with cangrelor. Cangrelor was associated with increased odds of complete reperfusion (aOR=5.86; 95%CI 1.57–26.62;p=0.013). ConclusionsIn this retrospective non-randomized cohort study, our findings suggest that low dose cangrelor has similar safety and increased rate of complete reperfusion compared to IV GP-IIb/IIIa inhibitors. Further prospective studies are warranted to confirm this association.

Multi-centric study for development and validation of a CT head rule for mild traumatic brain injury in direct oral anticoagulants: the HERO-M nomogram

BackgroundNomograms are easy-to-handle clinical tools which can help in estimating the risk of adverse outcome in certain population. This multi-center study aims to create and validate a simple and usable clinical prediction nomogram for individual risk of post-traumatic Intracranial Hemorrhage (ICH) after Mild Traumatic Brain Injury (MTBI) in patients treated with Direct Oral Anticoagulants (DOACs).MethodsFrom January 1, 2016 to December 31, 2019, all patients on DOACs evaluated for an MTBI in five Italian Emergency Departments were enrolled. A training set to develop the nomogram and a test set for validation were identified. The predictive ability of the nomogram was assessed using AUROC, calibration plot, and decision curve analysis.ResultsOf the 1425 patients in DOACs in the study cohort, 934 (65.5%) were included in the training set and 491 (34.5%) in the test set. Overall, the rate of post-traumatic ICH was 6.9% (7.0% training and 6.9% test set). In a multivariate analysis, major trauma dynamic (OR: 2.73, p = 0.016), post-traumatic loss of consciousness (OR: 3.78, p = 0.001), post-traumatic amnesia (OR: 4.15, p < 0.001), GCS < 15 (OR: 3.00, p < 0.001), visible trauma above the clavicles (OR: 3. 44, p < 0.001), a post-traumatic headache (OR: 2.71, p = 0.032), a previous history of neurosurgery (OR: 7.40, p < 0.001), and post-traumatic vomiting (OR: 3.94, p = 0.008) were independent risk factors for ICH. The nomogram demonstrated a good ability to predict the risk of ICH (AUROC: 0.803; CI95% 0.721–0.884), and its clinical application showed a net clinical benefit always superior to performing CT on all patients.ConclusionThe Hemorrhage Estimate Risk in Oral anticoagulation for Mild head trauma (HERO-M) nomogram was able to predict post-traumatic ICH and can be easily applied in the Emergency Department (ED).

Tenecteplase, 0.4 mg/kg, in Moderate and Severe Acute Ischemic Stroke: A Pooled Analysis of NOR-TEST and NOR-TEST 2A.

Background The optimal dose of tenecteplase in acute ischemic stroke remains to be defined. We present a pooled analysis of the 2 NOR-TESTs (Norwegian Tenecteplase Stroke Trials) exploring the efficacy and safety of tenecteplase, 0.4 mg/kg. Methods and Results We retrospectively reviewed 2 PROBE (Prospective Randomized Open, Blinded End-point) trials, NOR-TEST and NOR-TEST 2A. Patients were randomized to either tenecteplase, 0.4 mg/kg, or alteplase, 0.9 mg/kg. The primary end point was favorable functional outcome at 3 months (modified Rankin Scale score, 0-1) or return to baseline if prestroke modified Rankin Scale score was 2. Secondary end points included favorable functional and clinical outcome and safety data. The pooled analysis includes patients with National Institutes of Health Stroke Scale score ≥6 from both trials and an additional post hoc analysis of patients with National Institutes of Health Stroke Scale score ≤5 from NOR-TEST. The per-protocol analysis contains 483 patients, of whom 235 were assigned to tenecteplase and 248 were assigned to alteplase. In per-protocol analysis, functional outcome was better in the alteplase arm with cutoff modified Rankin Scale score of 2 (odds ratio [OR], 0.52 [95% CI, 0.33-0.80]; P=0.003) and expressed by ordinal shift analysis (OR, 1.64 [95% CI, 1.17-2.28]; P=0.004). Mortality at 3 months was higher in the tenecteplase arm (OR, 2.48 [95% CI, 1.20-5.10]; P=0.01). Mortality and intracranial hemorrhage rates were higher in the severe stroke group randomized to tenecteplase, whereas these rates were similar for alteplase and tenecteplase in moderate and mild stroke. Conclusions Tenecteplase, 0.4 mg/kg, is unsafe in moderate and severe stroke, and the risk of death and intracranial hemorrhage probably increases with stroke severity. A lower tenecteplase dose should be tested in future trials. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01949948, NCT03854500.

A Comparative Study of Hemorrhagic Conversion Patterns After Stroke Thrombolysis With Alteplase Versus Tenecteplase.

Tenecteplase is the thrombolytic drug of choice for acute ischemic stroke (AIS) as it has unique pharmacologic properties, along with results demonstrating its non-inferiority compared to alteplase. However, there are contradictory data concerning the risk of intracranial hemorrhage. The purpose of the study was to report the rate and patterns of symptomatic intracranial hemorrhage (sICH) in AIS patients after thrombolysis with tenecteplase compared to alteplase. This is a retrospective cohort study with data collected 90 days before and after the change from alteplase to tenecteplase from 15 Texas stroke centers. The primary endpoint is the incidence of sICH according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) and European Cooperative Acute Stroke Study III (ECASS-3) criteria. The secondary endpoints are the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBC). A total of 431 patients were eligible for thrombolytic therapy. Half of the cohort received alteplase (n=216), and the other half received tenecteplase (n=215). The average age of the alteplase group was 62.94 years old (SD=15.12) and 64.45 years old (SD=14.51) for the tenecteplase group. Seven patients in the alteplase group (3.2%) and 14 (6.5%) in the tenecteplase group had sICH, with an odds ratio of 1.44 (95% CI 0.60-3.43; P=0.41). An increased National Institutes of Health Stroke Scale (NIHSS) score on arrival (1.06; 95% CI 1.0004-1.131; P=0.04) was a statistically significant predictor of sICH. Tenecteplase was associated with a statistically significant increase in HBC-3 (P=0.040) over alteplase. Compared with alteplase, our study revealed a higher rate of sICH with tenecteplase that was not statistically significant and a higher rate of HBC-3 hemorrhages that was statistically significant. The proposed mechanism of bleeding is hemorrhagic conversion in clinically silent infarcts and contusions underlying the lesions. Further studies are needed to confirm our findings and determine predictive risk factors.

Dual antiplatelet therapy is associated with favorable outcome in acute minor stroke with an onset-to-door time beyond 24 h

In patients with noncardioembolic acute minor ischemic stroke (AMIS), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 24h after stroke onset was more effective than aspirin alone. This study investigated the efficacy and safety of DAPT in AMIS patients with an onset-to-door time (OTDT) of more than 24h. This was a retrospective analysis of a prospective stroke registry from 2015 to 2021. Patients with AMIS and an OTDT within seven days were classified into the Early (≤24h) and Late groups (>24h) according to the time of antiplatelet administration after stroke onset. In total, 691 patients were identified. Of these, 446 (64.5%) and 245 (35.5%) patients were classified into the Early and Late groups, respectively. The rates of recurrent infarction and symptomatic intracranial hemorrhage at 90 days were similar between the single antiplatelet therapy (SAPT) and DAPT subgroups in both the Early and Late groups. More patients in the DAPT subgroup had a favorable outcome (modified Rankin scale of 0-1) at 90 days in both Early (84.2% versus 75.0%, p=0.016) and Late (88.2% versus 76.9%, p=0.040) groups. DAPT was independently associated with a favorable outcome in both the Early (odds ratio, 1.95; 95% CI, 1.15-3.32; p=0.013) and Late (odds ratio, 2.72; 95% CI, 1.14-6.48; p=0.024) groups. In patients with AMIS and an OTDT of more than 24h, DAPT was associated with a favorable outcome at 90 days.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial

Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. EU Horizon 2020.

Systematic review and meta-analysis of the efficacy and safety of adjunctive use of tirofiban in patients treated with endovascular therapy for acute ischemic stroke at different embolic sites.

The use of tirofiban as an adjunct to endovascular therapy (EVT) for acute ischemic stroke has been controversial. We aimed to assess the differences in safety and efficacy of EVT adjuvant to tirofiban in patients with anterior circulation stroke (ACS) and posterior circulation stroke (PCS). We systematically searched Pubmed, Embase, Cochrane Library, and Web of Science. Cohort studies and randomized controlled trials that compared treatment with tirofiban combined with EVT and EVT alone were included in our meta-analysis. The safety outcomes were symptomatic intracranial hemorrhage, and 3-month mortality. The efficacy outcomes were good functional outcome, excellent functional outcome, and successful recanalization (mTICI ≥ 2b). We performed subgroup analyses of anterior and posterior circulation strokes. We included 15 studies with 4608 patients. For safety outcomes, tirofiban significantly reduced 3-month mortality in the ACS subgroup (odd ratio [OR] = 0.80, 95% confidence interval [CI] = 0.65-0.98, P = .03) without increasing the rate of symptomatic intracranial hemorrhage (OR = 1.12, 95% CI = 0.88-1.44, P = .35). In the PCS subgroup, tirofiban significantly reduced 3-month mortality (OR = 0.63, 95% CI = 0.50-0.80, P = .0001) and symptomatic intracranial hemorrhage (OR = 0.60, 95% CI = 0.37-0.95, P = .03). For efficacy outcomes, in the ACS subgroup, tirofiban significantly improved good functional outcome (OR = 1.24, 95% CI = 1.06-1.45, P = .008) but did not improve recanalization (OR = 1.17, 95% CI = 0.93-1.47, P = .17) and excellent functional outcome (OR = 1.19, 95% CI = 0.97-1.46, P = .10). In the PCS subgroup, tirofiban significantly improved recanalization rate (OR = 1.94, 95% CI = 1.43-2.65, P < .0001) and did not improve good functional outcome (OR = 1.03, 95% CI = 0.81-1.30, P = .81) and excellent functional outcome (OR = 0.84, 95% CI = 0.58-1.20, P = .34). In acute ischemic stroke patients undergoing EVT, tirofiban improves good functional outcomes in ACS patients and increases recanalization rates in PCS patients on the 1 hand, reduces mortality, and does not increase the risk of symptomatic intracranial hemorrhage on the other. Tirofiban is safe and effective in both anterior circulation stroke and posterior circulation stroke patients undergoing EVT. More large multicentre randomized controlled studies are needed in the future.

Efficacy and Safety Outcomes for Acute Ischemic Stroke Patients Treated with Intravenous Infusion of Tirofiban After Emergent Carotid Artery Stenting

IntroductionEmergent stenting of the extracranial internal carotid artery (ICA) in stroke patients requires antiplatelet therapy to prevent in-stent thrombosis with a higher risk of intracranial haemorrhage.Aim of the StudyAssess the efficacy and safety of emergent carotid stenting with intravenous tirofiban in acute ischemic stroke patients.MethodsPrimary endpoint: symptomatic hemorrhage. Secondary endpoints: 90-day functional outcome and mortality.ResultsOf the 62 patients, 21 (34%) received tirofiban as a single antiplatelet, and 41 (66%) received combined therapy. Premedication with anticoagulants and antiplatelets was significantly more frequent in the tirofiban-only group. The rate of symptomatic haemorrhage was significantly lower in the tirofiban-only group than in the combined group (4.8% vs. 27%, p = 0.046). The patients with tirofiban alone had a significantly better functional outcome at day 90 than the combined group (52% vs. 24%, p = 0.028). Mortality was equal (24%) in both groups. Pre-interventional NIHSS score (p = 0.003), significant blood pressure fluctuations (p = 0.012), tandem occlusion (p = 0.023), and thrombolysis (p = 0.044) showed relevant influence on the rate of symptomatic hemorrhage in the entire patient cohort.ConclusionsA single antiplatelet therapy with tirofiban regardless of the premedication may improve the functional outcome in patients with stroke due to acute extracranial carotid lesion and emergent carotid stenting with lower rates of serious intracranial haemorrhage.For patients with high pre-interventional NIHSS score, tandem occlusion and after pre-interventional thrombolysis, caution is advised. Additionally, strict blood pressure monitoring should be conducted during the first 72 h after intervention.

Bridging therapy improves functional outcomes and reduces 90-day mortality compared with direct endovascular thrombectomy in patients with acute posterior ischemic stroke: a systematic review and meta-analysis.

It remains unclear whether bridging therapy can achieve better neurologic outcomes than direct endovascular thrombectomy (EVT) in patients with posterior ischemic stroke. We systematically searched PubMed, EMBASE, and Cochrane databases with posterior artery occlusion treated with bridging therapy vs. EVT. Efficacy was assessed based on functional independence at 90days and successful recanalization, whereas safety was assessed by mortality, rate of symptomatic intracranial hemorrhage (sICH), and occurrence of any hemorrhage. All data were analyzed with Review Manager software v5.3 and the risk of bias was determined using the Methodological Index for Non-randomized Studies. We included 17 studies with a total of 3278 patients (1211 in the bridging therapy group and 2067 in the EVT group). Patients in the bridging group had a better functional outcome at 90days, as evidenced by a higher proportion with a Modified Rankin Scale (mRS) score of 0-2 compared with the EVT group (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.54-2.19, P < 0.01), while no difference in mRS score of 0-3 (OR = 1.18, 95% CI: 0.96-1.45, P = 0.11). Patients in the bridging therapy group also had lower 90-day mortality rate (OR = 0.75, 95% CI: 0.59-0.95, P = 0.02). There were no significant differences between groups in rates of successful recanalization (OR = 0.96, 95% CI: 0.74-1.25, P = 0.77), sICH (OR = 1.27, 95% CI: 0.86-1.89, P = 0.24), and hemorrhage (OR = 1.22, 95% CI: 0.60-2.50, P = 0.58). Among patients with posterior ischemic stroke, bridging therapy may be superior to EVT in achieving a good functional outcome and lowering the mortality without increasing the risks of hemorrhage.

Safety of Intravenous Cangrelor Versus Dual Oral Antiplatelet Loading Therapy in Endovascular Treatment of Tandem Lesions: An Observational Cohort Study

Background Procedural intravenous cangrelor has been proposed as an effective platelet inhibition strategy for stenting in acute ischemic stroke. We aimed to compare the safety profile of low‐dose intravenous cangrelor versus dual oral antiplatelet therapy (DAPT) loading in patients with acute cervical tandem lesions. Methods We retrospectively identified cases from an international multicenter cohort who underwent intraprocedural administration of intravenous cangrelor (15 μg/kg followed by an infusion of 2 μg/kg per min) or DAPT loading during acute tandem lesions intervention. Safety outcomes included rates of symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, and in‐stent thrombosis. Inverse probability of treatment weighting matching was used to reduce confounding. Results From 691 patients, we included 195 patients, 30 of whom received intravenous cangrelor and 165 DAPT. The DAPT regimens were aspirin+clopidogrel (93.3%) or aspirin+ticagrelor (6.6%). After inverse probability of treatment weighting, the patients treated with cangrelor were not at greater odds of symptomatic intracranial hemorrhage (odds ratio [OR], 1.30 [95% CI, 0.09–17.3]; P =0.837), symptomatic intracranial hemorrhage–parenchymal hematoma type 2 (OR, 0.54 [95% CI, 0.05–4.98]; P =0.589), or petechial hemorrhage (OR, 1.11 [95% CI, 0.38–3.28]; P =0.836). Similarly, the rate of in‐stent thrombosis was not significantly different between the 2 groups (1.8% versus 0%; P =0.911). Conclusion Cangrelor at the half dose of the myocardial infarction protocol showed a similar safety profile compared with the commonly used DAPT loading protocols in patients with acute tandem lesions. Further studies with larger samples are warranted to elucidate the safety of antiplatelet therapy in tandem lesions.