Rate Of Intracranial Hemorrhage Research Articles

Predictors and outcomes of intracranial hemorrhage in 58,000 patients with atrial fibrillation on oral anticoagulation: insights from COMBINE-AF

Abstract Background Among anticoagulated patients with atrial fibrillation (AF), intracranial hemorrhage (ICH) is the leading cause of bleeding-related death and disability. The COMBINE-AF database has patient-level data from four major randomized-controlled trials [ROCKET-AF (rivaroxaban), RE-LY (dabigatran), ENGAGE-TIMI 48 (edoxaban), ARISTOTLE (apixaban)] of direct oral anticoagulants (DOACs) versus warfarin in patients with AF. Purpose/Methods We investigated the rates, predictors, and mortality of ICH in patients randomized to DOAC (rivaroxaban, dabigatran, edoxaban, apixaban) or warfarin. ICH was subclassified as subdural or non-subdural (intracerebral, intraventricular, subarachnoid, epidural). Multivariable Cox models were used to identify predictors of ICH. Frequencies and fatality rates of ICH were calculated and displayed as Kaplan-Meier curves. Results In COMBINE-AF, there were 58,634 patients randomized to either DOAC (n=29,362) or warfarin (n=29,272). The mean age was 70.5 years, 37% were female, and 81% were White. The mean CHA2DS2-VASc score was 2.6, 43% of patients had a history of smoking, 31% had diabetes, and 29% had prior stroke/TIA. After a mean of 32 months, ICH occurred in 593 patients (1.01%, 0.58 per 100-patient years, 95% CI [0.54, 0.63]). The most significant independent predictors of ICH in order of importance were: treatment with warfarin, older age, prior stroke/TIA, enrollment in Asia, antiplatelet use at randomization, and history/risk of falls (Figure 1). Mortality after ICH was 48.4% (287/593 participants), with a majority of deaths (82%) occurring within 30 days of ICH event. Non-subdural ICH was more common than subdural ICH (73% vs 25%) and had a higher risk of death (Figure 2). Participants randomized to DOAC had a lower risk of both subdural and non-subdural ICH than those treated with warfarin; however, mortality rates after ICH were similar regardless of anticoagulant type. Conclusion ICH is an uncommon but devastating complication of oral anticoagulation in patients with atrial fibrillation. The mortality rate following ICH is high, particularly following non-subdural ICH. To reduce the risk of ICH, clinicians should consider using DOACs over warfarin and carefully evaluate the need for antiplatelet therapy, particularly in patients with other significant predictors of ICH such as prior stroke, advanced age, residence in Asia, and history of falls.Predictors of Intracranial Hemorrhage90-Day Mortality after ICH

Efficacy and safety of different oral anticoagulants for stroke prevention in older patients with atrial fibrillation: A network meta-analysis.

Various oral anticoagulants have been used for stroke prevention in older patients with atrial fibrillation (AF). However, the optimal anticoagulants for stroke prevention has not yet been developed. We performed a systematic review and network meta-analysis to determine the optimal instructions. We searched for randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Library without restriction for publication date or language at January 2024. Any RCTs that compared the effectiveness of a direct oral anticoagulant and a vitamin K antagonist (VKA) for stroke prevention in older patients with AF were included in this network meta-analysis. The Bayesian network meta-analysis used a random effects model and surface under the cumulative ranking curve analysis to rank results. All analyses were done using R software with gemtc package, with statistical significance set at P < .05. We included 7 RCTs (79,003 patients) comparing 8 different instructions including Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, Edoxaban 60 mg, Rivaroxaban 15 mg, Rivaroxaban 20 mg, and VKA. Apixaban 5 mg, Dabigatran 110 mg, and Dabigatran 150 mg was more effective than the VKA for reducing stroke or systemic embolism risks, and the difference was statistically significant (P < .05). Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, and Edoxaban 60 mg was associated with a reduction of the intracranial hemorrhage rate than the VKA (P < .05). The surface under the cumulative ranking curve shows that Dabigatran 110 mg ranked first for reducing stroke or systemic embolism risks. Edoxaban 60 mg ranked first for major bleeding. Dabigatran 110 mg ranked first for intracranial hemorrhage. Apixaban 5 mg ranked first for all bleeding events. Direct oral anticoagulants were found to have lower rates of thromboembolic events compared to VKAs in older patients with AF. Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, and Edoxaban 60 mg were also associated with a reduction of intracranial hemorrhage than VKA.

Intravenous thrombolysis in patients on direct oral anticoagulants: A survey of NIH StrokeNet sites

BackgroundPatients with suspected ischemic stroke and use of Direct Oral Anticoagulants (DOACs) within 48 h are excluded from thrombolysis. We aimed to determine practice patterns across institutions in the NIH StrokeNet, a network of hospitals to conduct NIH-funded stroke clinical trials, in the United States. MethodsA survey was sent electronically to all NIH StrokeNet regional coordinating centers. The survey questions were geared towards understanding practice patterns with intravenous thrombolysis use in patients on DOACs. We reported proportions and percentages answers to the questions. We compared the likelihood of thrombolysis use in patients with recent DOAC ingestion (never vs. all other responses) across characteristics of survey responder using Chi Square. ResultsA total of 83 site principal investigators completed the survey; 78.3 % would never give thrombolysis to an otherwise eligible patients within 12-24 h from last DOAC ingestion and 54.2 % would never give thrombolysis to an otherwise eligible patient within 24-48 h from last DOAC ingestion. A higher proportion of vascular neurologists would never give thrombolysis in patients with DOAC ingestion within 12-48 h compared to other subspecialties (60.7 % vs. 36.4 %, p = 0.05). Nearly, 80 % would change their practice if a well-designed prospective study demonstrated that the symptomatic intracranial hemorrhage rate is not >5 %. ConclusionsA well-designed prospective study with a set safety threshold is likely to change practice patterns in giving thrombolysis in patients with recent DOAC ingestion, particularly among vascular neurologists who are more likely to never give thrombolysis in this setting.

Thrombolysis After Dabigatran Reversal for Acute Ischemic Stroke: A National Registry-Based Study and Meta-Analysis.

Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT. A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment. Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I2 = 24%) and 18% (95% CI 10-27; I2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I2 = 69%) and 70% (95% CI 57-81; I2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I2 = 27%). IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.

Thrombolysis in wake-up stroke based on MRI mismatch

ObjectivesWake-up stroke (WUPS) patients can be selected to intravenous thrombolysis (IVT) treatment based on the Magnetic Resonance Imaging (MRI) mismatch concept. However, recent studies suggest the introduction of modified MRI mismatch criteria, allowing IVT in WUPS patients with a partial mismatch. Material and methodsWUPS patients treated with IVT in the NOR-TEST trial and consecutively thereafter at Stavanger University Hospital were included in this study. Patient selection for treatment was performed based on the clinical presentation and the MRI DWI/FLAIR mismatch criteria. MRI examinations were reassessed according to the modified DWI-FLAIR mismatch criteria, allowing partial mismatch. Improvement in NIHSS and mRS at 3 months were used to analyze clinical outcome, and the rate of intracranial hemorrhage (ICH) to analyze safety. Results78 WUPS patients were treated with IVT. Only 68 of these patients were independent pre-stroke and included in the clinical analysis. When reassessing the MRI examinations, 41 (60 %) were rated as DWI/ FLAIR mismatch, 14 (21 %) as partial mismatch and 13 (19 %) as match. The results show that the patient groups had a mRS score 0–1 at 3 months measured as primary outcome to respectively 27 (65.9 %), 11 (78.6 %) and 8 (61.5 %); (P = 0.629). The mismatch group showed the best clinical improvement (3-points NIHSS reduction, p = 0.005). No ICH was seen in any of the groups. ConclusionOur study extended the mismatch concept in clinical praxis to treat WUPS patients with partial mismatch, showing the best clinical outcome in the mismatch group.

Ethnic Differences in the Safety and Efficacy of Tenecteplase Versus Alteplase for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke. Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR). From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P<0.01) in Asian (RR: 1.91, 95% confidence interval [CI]: 1.30 to 2.80) versus Caucasian patients (RR: 0.99, 95% CI: 0.87 to 1.14). However, Asian patients (RR: 1.18, 95% CI: 0.87 to 1.62) had significantly higher (P=0.01) rates of mortality compared with Caucasian patients (RR: 1.10, 95% CI: 1.00 to 1.22). Caucasian patients were also more likely to attain a modified Rankin Scale (mRS) score of 0 to 2 at follow-up (RR: 1.14, 95% CI, 1.10 to 1.19) compared with Asian (RR: 1.00, 95% CI, 0.95 to 1.05) patients. There was no significant difference in the rate of symptomatic intracranial hemorrhage (P=0.20) and any intracranial hemorrhage (P=0.83) between Asian and Caucasian patients. Tenecteplase was associated with significantly higher rates of complete recanalization in Asian patients compared with Caucasian patients. However, tenecteplase was associated with higher rates of mortality and lower rates of mRS 0 to 2 in Asian patients compared with Caucasian patients. It may be beneficial to study the variations in response to tenecteplase among patients of different ethnic groups in large prospective cohort studies.

Safety and effectiveness of SOFIA/SOFIA PLUS for direct aspiration as first line treatment in patients with acute anterior ischemic stroke: results from the prospective, multicentric SESAME study.

Mechanical thrombectomy is a cornerstone treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO), yet the optimal technique remains debated. The SOFIA/SOFIA PLUS catheter has emerged as a promising tool for direct aspiration thrombectomy. This prospective multi-center study, adhering Good-Clinical-Practice guidelines, aimed to evaluate the safety and efficacy of the SOFIA/SOFIA PLUS catheter for direct aspiration as a first-line treatment technique in patients with acute anterior circulation LVO. Between 10/2017 and 12/2021, 246 consecutive patients presenting with AIS due to anterior circulation LVO were enrolled from 14 European centers. Primary treatment with SOFIA catheters was performed within 6 h of symptom onset. Clinical and radiological data were collected, and statistical analyses were conducted. The mean age of the included patients was 71.6 ± 13.9 years, with 44.7% being male. Primary aspiration achieved complete recanalization in 72.8% of patients, with functional independence observed in 63.8% after 90 days. Secondary outcomes included a median NIHSS of 4 at 24 h post-procedure, median ASPECTS of 7 on follow-up imaging, and a mortality rate of 24.4% at 90 days. No device malfunctions were observed, and the rate of symptomatic intracranial hemorrhage was 4.4%. Primary aspiration with the SOFIA/SOFIA PLUS catheter demonstrates favorable safety and efficacy profiles in the treatment of anterior circulation LVO. These findings support the utilization of this technique as a first-line approach in mechanical thrombectomy for AIS, contributing to the growing body of evidence endorsing the effectiveness of direct aspiration thrombectomy in stroke management.

Rates of strokes in Californians with sickle cell disease in the post-STOP era

AbstractNeurovascular complications, including strokes and transient ischemic attacks (TIAs), are common and cause significant morbidity in individuals with sickle cell disease (SCD). The Stroke Prevention Trial in Sickle Cell Anemia (STOP) (1998) established chronic transfusions as the standard of care for children with SCD at high risk for stroke. Using statewide emergency department and hospitalization data from the California Department of Health Care Access and Innovation (1991-2019), we determined the cumulative incidence and rates of primary and recurrent strokes and TIAs in people with SCD before and after the STOP trial. For the 7636 patients included in our SCD cohort, the cumulative incidence of the first ischemic stroke was 2.1% (95% confidence interval [CI], 1.8-2.4) by the age of 20 years and 13.5% (95% CI, 12.3-14.7) by the age of 60 years. The cumulative incidence of the first intracranial hemorrhage (ICH) was 0.5% (95% CI, 0.4-0.7) by the age of 20 years and 6.8% (95% CI, 5.9-7.7) by the age of 60 years. Ischemic stroke rates increased in children (age <18 years; 234.9 vs 165.1 per 100 000 PY; P = .012) and adults (age 31-50 years; 431.1 vs 303.2 per 100 000 PY; P = .031) in 2010 to 2019 when compared with the preceding decade. There was an increase in the rates of ICH in those aged 18 to 30 years and TIA in children <18 years from 2010 to 2019 when compared with the previous decade. Risk factors for stroke and TIA included increasing age, hypertension, and hyperlipidemia. These findings underscore the need for prevention of strokes in adults with SCD and suggest an emphasis on the management of modifiable cerebrovascular risk factors that have been demonstrated to be effective in the general population.

A prospective, randomized, controlled, interventional clinical trial to evaluate the safety and efficacy of the medical monopoint reperfusion system for aspiration thrombectomy in acute ischemic stroke patients (SUMMIT MAX): Trial rationale and design.

Treatment of large vessel occlusion (LVO) using mechanical thrombectomy with or without intravenous thrombolysis has demonstrated better outcomes compared to medical treatment alone. Large-bore aspiration catheters have been recently introduced. Their effectiveness and safety have not been demonstrated in a randomized trial. The SUMMIT MAX study is designed to address this question. SUMMIT MAX is a randomized controlled trial where the effectiveness and safety of the large-bore Monopoint Reperfusion system (Route 92 Medical, San Mateo, CA), will be compared to the currently largest available FDA-cleared aspiration thrombectomy device the AXS Vecta Aspiration system (Stryker Neurovascular, Fremont, CA). The study is a multi-center, prospective, randomized, controlled, interventional, open label clinical trial. The hypothesis is that the effectiveness measured by the recanalization rate (modified thrombolysis in cerebrovascular infarction - mTICI) and safety measured by symptomatic intracranial hemorrhage rate (sICH) of the medical monopoint reperfusion system is non-inferior to the AXS Vecta Aspiration system. Up to 250 subjects are enrolled with at least 50% of subjects enrolled by US sites. The primary effectiveness endpoint is successful arterial revascularization defined as an mTICI score ≥ 2b after use of the assigned device adjudicated by an independent core lab. The primary safety endpoint is defined as sICH within 24 h (-8/+24) post-procedure. Secondary endpoints include successful arterial revascularization defined as a mTICI score ≥ 2b after use of the assigned device with or without adjunctive therapy; device-related serious adverse events; all asymptomatic hemorrhages; time from groin puncture to final angiogram; and rate of first pass effect defined as mTICI 2b after first pass with the assigned device stratified by age (≤85, ≥ 86). SUMMIT MAX is a randomized controlled trial comparing the effectiveness and safety of a new large bore class of aspiration devices to the currently largest FDA-cleared aspiration device available.

Clinical comparison of aspiration to stentriever-mediated aspiration thrombectomy for M2 occlusions

ObjectiveWhile revascularization for M2 occlusions is generally recommended and considered beneficial, the optimal approach (aspiration vs stentriever/combined) is less well defined in the literature. We sought to compare outcomes after thrombectomy with manual aspiration thrombectomy alone (MAT) or stentriever-mediated aspiration thrombectomy (SMAT) Materials and MethodsTo circumvent inter-operator technical variability, patients underwent thrombectomy for M2 occlusions by a single operator and were stratified by first pass approach: manual aspiration thrombectomy (MAT/aspiration alone) and stentriever-mediated manual aspiration thrombectomy (SMAT/combination). Efficacy outcomes included good reperfusion (mTICI score ≥2b) and a favorable 90-day functional outcome (mRS score of ≤2). Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage. ResultsOne hundred three patients were identified: 57 underwent MAT whereas 46 underwent SMAT. Good reperfusion (TICI 2b or greater) was comparable between groups (93.5 % vs. 87.7 %, P=0.33). The intracranial hemorrhage rate was higher with SMAT compared to MAT (13 % vs. 1.8 %, P=0.04). Puncture-to-recanalization time was longer in SMAT (34.4 vs. 19.9 minutes, P<0.001). In multivariable analysis, complete or good reperfusion was associated with shorter puncture-recanalization time (adjusted odds ratio [aOR], 0.85) or less total passes (aOR, 0.58), respectively. In a propensity score matched analysis of 66 patients with comparable baseline and technical efficiency, the safety outcomes were not different between SMAT and MAT groups. ConclusionsSMAT compared with MAT did not result in an improved revascularization rate or functional outcome, while it was related to more hemorrhagic complications and mortality. Given cost and time savings with manual aspiration alone, this approach may be optimal as first line for M2 occlusions.

Performance and clinical outcomes in telestroke remain robust during the COVID-pandemic: insight into the NEVAS network.

The COVID-19 pandemic had significant impact on global healthcare, including stroke management. Telemedical stroke networks have emerged with positive results for patient outcome in rural areas without stroke expertise. However, telestroke faced enormous on-site challenges during the pandemic. So far, data on performance and clinical outcomes in telestroke settings during the COVID-pandemic are scarce. We retrospectively analyzed data from stroke patients treated in four spoke hospitals of the Bavarian telestroke network NEVAS in 2020-2021 and 2019 as reference year and compared the 3years for various parameters. Primary outcome was functional outcome according to the modified Rankin scale (mRS). Secondary outcome parameters included time intervals, periprocedural intracranial hemorrhage rates, and mortality. In 2019-2021, 2820 patients were treated for acute ischemic stroke with an admission decrease of 10% during the pandemic. Of those, 241 received only IVT and 204 were transferred to our center for MT. Door-to-imaging, door-to-needle, and symptom-onset-to-groin times remained comparable in the 3years. Complication rates remained at a low level. Good clinical outcome rates (mRS 0-2) at discharge remained stable for all stroke patients (82-84%) and for those treated with IVT (64-77%). Good clinical outcome rates at 3month follow-up for MT patients declined in 2020 (23% vs. 35% in 2019) but recovered again in 2021 (42%). Mortality rates did not increase for all patient groups analyzed. Stroke care remained robust during the COVID-pandemic within our network, indicating that well-established telestroke networks can overcome unexpected critical challenges such as a pandemic, guaranteeing best practice stroke care in rural areas.

18FFlutemetamol-PET Aided Classification of Cerebral Amyloid Angiopathy: A Multicenter Study.

Cerebral amyloid angiopathy (CAA)-related features on neuroimaging often coexist with signs of arteriolosclerosis-small vessel disease on neuroimaging in people with intracranial hemorrhage (ICH). This study aimed at defining the value of amyloid pathology detected by 18Fflutemetamol PET in reclassification and stratification of risk of bleeding in people with mixed CAA-arteriolosclerosis features. We included consecutive patients admitted to 2 institutions (2018-2023) with spontaneous symptomatic ICH, subarachnoid hemorrhage (SAH), transient focal neurologic episodes (TFNE), or cognitive impairment and MRI showing CAA hallmarks. All patients underwent brain magnetic resonance imaging (MRI) with susceptibility weighted imaging and 18Fflutemetamol PET imaging and were followed up for at least 1 year. We compared cases with CAA and arteriolosclerosis + CAA features and defined long-term outcomes (composite outcome including death, ICH, ischemic stroke, SAH, TFNE) depending on PET status (CAA/amyloid pathology vs arteriolosclerosis-predominant groups). Among 47 patients, according to PET and MRI imaging, 38 patients were reclassified in the CAA/amyloid pathology group and 9 in the arteriolosclerosis-predominant group, with similar cardiovascular risk factors but a significantly higher lobar microbleed burden for the former group. The CAA/amyloid pathology group had higher rates of composite outcome (43.9 vs 11.1 events per 100 patient-year; p = 0.039) and ICH (36.5 vs 5.6 events per 100 patient-years; p = 0.04) compared with the arteriolosclerosis-predominant group. 18FFlutemetamol PET imaging can help in reclassification of mixed arteriolosclerosis + CAA into CAA/amyloid pathology and arteriolosclerosis-predominant, with implications on long-term risk of recurrent events. This study provides Class IV evidence that 18Fflutemetamol PET can distinguish between CAA + arteriolosclerosis and arteriolosclerosis-predominant pathology.

Endovascular thrombectomy versus medical management for acute basilar artery occlusion stroke in the elderly.

The efficacy and safety of endovascular thrombectomy (EVT) for elderly basilar artery occlusion (BAO) stroke patients is unclear. This was an explorative retrospective analysis of the 2016-21 National Inpatient Sample in the United States. Elderly BAO stroke patients (80 years or older) with NIH stroke scale of at least 5 were included. Primary outcome was discharge to home. Secondary outcomes include in-hospital mortality and intracranial hemorrhage (ICH). Outcomes were compared between patients treated with EVT and those treated with medical management (MM) alone. Propensity score matching (PSM) was performed to control for confounders. Subgroup analyses were conducted for patients who did and did not receive intravenous thrombolysis (IVT). 2,520 elderly BAO patients were identified; 830 received EVT, and 1,690 received MM alone. After PSM, 1,115 patients and 715 patients remained in the MM and EVT groups, respectively. Compared to PSM controls, EVT was not significantly associated with different rates of home discharge (17.5% vs. 12.2%, OR 1.36 [95%CI 0.76-2.44], p=0.30) or in-hospital mortality (31.5% vs. 32.9%, OR 1.00 [95%CI 0.63-1.60], p=0.99), but it was significantly associated with higher rates of ICH (18.2% vs. 7.3%, OR 2.69 [95%CI 1.41- 5.15], p=0.003). Among patients who did not receive IVT, EVT was significantly associated with higher rates of home discharge (21.5% vs. 11.5%, OR 1.93 [95%CI 1.02-3.66], p=0.044), whereas EVT was not significantly associated with the same among those treated with IVT (5.6% vs. 15.0%, OR 0.28 [95%CI 0.05-1.46], p=0.13). Interaction analysis revealed that IVT was a negative modulator of EVT's positive association with home discharge (interaction p=0.031). EVT was not significantly associated with more favorable hospitalization outcomes for elderly BAO stroke patients, and it was significantly associated with increased risk of ICH. EVT may be an effective treatment for patients who did not receive IVT. EVT = endovascular thrombectomy; BAO = basilar artery occlusion; ICH = intracranial hemorrhage; MM = medical management; PSM = propensity score matching; IVT = intravenous thrombolysis.

Intracranial artery calcification: Frequency, determinants, and modification of outcomes from endovascular thrombectomy

IntroductionIntracranial artery calcification (ICAC) is a common finding on computed tomography (CT) in patients presenting with large vessel occlusion acute ischemic stroke (LVO-AIS) and could serve as a useful biomarker of intracranial atherosclerosis and altered intracranial vessel pliability in patients undergoing endovascular thrombectomy (EVT). MethodsThis was a retrospective cohort study analyzing consecutive patients undergoing CT head prior to EVT between 2016 and 2020. Extent of ICAC proximal to the target vessel was scored using a validated grading scale examining thickness and circumferential extent of calcifications. The relationship between 3 levels of ICAC burden and procedural, clinical, and safety outcomes was analyzed. ResultsAmong 86 patients meeting inclusion criteria, ICAC of any degree was present in 72.1 %. Median ICAC score was 3 [IQR 0-4]. There was a U-shaped association between ICAC score and successful reperfusion: 90.9 %, 65.7 %, and 94.4 % in the low, intermediate, and high ICAC score groups, respectively (p = 0.008). Use of rescue intervention, most often angioplasty and stenting, was greatest in the high ICAC score group: 3.0 % vs. 5.7 % vs. 22.2 % (p = 0.05). Functional independence at 90 days did not differ significantly among groups (41.7 % vs. 31.0 % vs. 15.4 %, p = 0.26), nor did rates of symptomatic intracranial hemorrhage (15.2 % vs. 14.3 % vs. 16.7 %, p = 0.97). ConclusionsICAC is seen on CT in nearly three-quarters of patients with LVO-AIS. Extent of ICAC has a U-shaped association with successful reperfusion, in part due to more frequent use of rescue interventions in patients with extensive ICAC.

A pragmatic, stepped-wedge, hybrid type II trial of interoperable clinical decision support to improve venous thromboembolism prophylaxis for patients with traumatic brain injury

BackgroundVenous thromboembolism (VTE) is a preventable medical condition which has substantial impact on patient morbidity, mortality, and disability. Unfortunately, adherence to the published best practices for VTE prevention, based on patient centered outcomes research (PCOR), is highly variable across U.S. hospitals, which represents a gap between current evidence and clinical practice leading to adverse patient outcomes.This gap is especially large in the case of traumatic brain injury (TBI), where reluctance to initiate VTE prevention due to concerns for potentially increasing the rates of intracranial bleeding drives poor rates of VTE prophylaxis. This is despite research which has shown early initiation of VTE prophylaxis to be safe in TBI without increased risk of delayed neurosurgical intervention or death. Clinical decision support (CDS) is an indispensable solution to close this practice gap; however, design and implementation barriers hinder CDS adoption and successful scaling across health systems. Clinical practice guidelines (CPGs) informed by PCOR evidence can be deployed using CDS systems to improve the evidence to practice gap. In the Scaling AcceptabLE cDs (SCALED) study, we will implement a VTE prevention CPG within an interoperable CDS system and evaluate both CPG effectiveness (improved clinical outcomes) and CDS implementation.MethodsThe SCALED trial is a hybrid type 2 randomized stepped wedge effectiveness-implementation trial to scale the CDS across 4 heterogeneous healthcare systems. Trial outcomes will be assessed using the RE2-AIM planning and evaluation framework. Efforts will be made to ensure implementation consistency. Nonetheless, it is expected that CDS adoption will vary across each site. To assess these differences, we will evaluate implementation processes across trial sites using the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework (a determinant framework) using mixed-methods. Finally, it is critical that PCOR CPGs are maintained as evidence evolves. To date, an accepted process for evidence maintenance does not exist. We will pilot a “Living Guideline” process model for the VTE prevention CDS system.DiscussionThe stepped wedge hybrid type 2 trial will provide evidence regarding the effectiveness of CDS based on the Berne-Norwood criteria for VTE prevention in patients with TBI. Additionally, it will provide evidence regarding a successful strategy to scale interoperable CDS systems across U.S. healthcare systems, advancing both the fields of implementation science and health informatics.Trial registrationClinicaltrials.gov– NCT05628207. Prospectively registered 11/28/2022, https://classic.clinicaltrials.gov/ct2/show/NCT05628207.

Effect of Stroke Etiology on Endovascular Treatment for Acute Basilar-Artery Occlusion: A Post Hoc Analysis of the ATTENTION Randomized Trial.

Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies. The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute BAO were classified into 3 groups according to stroke etiology (large-artery atherosclerosis [LAA], cardioembolism, and undetermined cause/other determined cause [UC/ODC]). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. A total of 340 patients with BAO were included, 150 (44.1%) had LAA, 72 (21.2%) had cardioembolism, and 118 (34.7%) had UC/ODC. For patients treated with BMT plus EVT and BMT alone, respectively, the rate of favorable outcome at 90 days was 49.1% and 23.8% in the LAA group (odds ratio, 3.08 [95% CI, 1.38-6.89]); 52.2% and 30.8% in the cardioembolism group (odds ratio, 2.45 [95% CI, 0.89-6.77]); and 37.5% and 17.4% in the UC/ODC group (odds ratio, 2.85 [95% CI, 1.16-7.01]), with P=0.89 for the stroke etiology×treatment interaction. The rate of symptomatic intracranial hemorrhage in EVT-treated patients with LAA, cardioembolism, and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the BMT-treated patients. Lower 90-day mortality was observed in patients with EVT compared with BMT alone across 3 etiology groups. Among patients with acute BAO, EVT compared with BMT alone might be associated with favorable outcomes and lower 90-day mortality, regardless of cardioembolism, LAA, or UC/ODC etiologies. The influence of stroke etiology on the benefit of EVT should be explored by further trials. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04751708.

Antithrombin III Levels and Outcomes Among Patients With Trauma

Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma. To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma. This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024. The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)-free days, hemorrhage, venous thromboembolic events, and mortality. The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10-6), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10-6) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10-6). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT. In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.

Endovascular thrombectomy versus medical management for moderate-to-severe anterior cerebral artery occlusion stroke.

There are no established patient selection criteria for endovascular thrombectomy (EVT) for anterior cerebral artery (ACA) stroke. This was a retrospective cohort study of the 2016-2020 National Inpatient Sample in the United States. Isolated ACA-occlusion stroke patients with moderate-to-severe stroke symptoms (NIH stroke scale [NIHSS] ≥ 6) were included. Primary outcome was hospital discharge to home with self-care. Secondary outcomes include in-hospital mortality and intracranial hemorrhage (ICH). Confounders were accounted for by multivariable logistic regression. 6685 patients were included; 335 received EVT. Compared to medical management (MM), EVT patients were younger (mean 67.2 versus 72.2years; p = 0.014) and had higher NIHSS (mean 16.0 versus 12.5; p < 0.001). EVT was numerically but not statistically significantly associated with higher odds of home discharge compared to MM (aOR 2.26 [95%CI 0.99-5.17], p = 0.053). EVT was significantly associated with higher odds of home discharge among patients with NIHSS 10 or greater (aOR 3.35 [95%CI 1.06-10.58], p = 0.039), those who did not receive prior thrombolysis (aOR 3.96 [95%CI 1.53-10.23], p = 0.005), and those with embolic stroke etiology (aOR 4.03 [95%CI 1.21-13.47], p = 0.024). EVT was not significantly associated with higher rates of mortality (aOR 1.93 [95%CI 0.80-4.63], p = 0.14); however, it was significantly associated with higher rates of ICH (22.4% vs. 8.5%, p < 0.001). EVT was associated with higher odds of favorable short-term outcomes for moderate-to-severe ACA-occlusion stroke in select patients. Future studies are needed to confirm the efficacy of EVT in terms of longer term neurological outcomes.

Endovascular therapy in patients with a large ischemic volume at presentation: An aggregate patient-level analysis

IntroductionRecently, four randomized controlled trials (RCTs) have demonstrated the benefits of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) and a large ischemic core at baseline (LIC). The purpose of this study was to investigate the features influencing the clinical outcome and the benefits of mechanical thrombectomy in this subgroup. MethodsWe conducted a multicenter retrospective aggregate cohort study of patients with AIS-LVO and a LIC, assessed with quantitative core volume measures, treated with MT between 2012 and 2019. The data were queried through four registries, including patients with core volumes ≥50cc. Multivariable logistic regression models were employed to determine factors independently associated with clinical outcomes in patients with successful recanalization (modified-Thrombolysis-in-Cerebral-Infarction-score, mTICI=2b-3) and unsuccessful recanalization group (mTICI=0–2a). The primary endpoint was a favorable functional outcome at day-90, defined as a modified Rankin scale (mRS) of 0–3, accounting for the inherent severity of AIS with baseline LIC. Secondary outcomes included functional independence (mRS 0–2) at day-90, mortality, and symptomatic Intracranial Hemorrhage (sICH). ResultsA total of 460 patients were included (mean age 66±14.2 years; 39.6 % females). The mean baseline NIHSS was 20±5.2, and the core volume was 103.2±54.6 ml. Overall, 39.8 % (183/460) of patients achieved a favorable outcome at day-90 (mRS 0–3). Successful recanalization was significantly associated with a more frequent favorable outcome (aOR, 4.79; 95 %CI, 2.73–8.38; P<0.01) and functional independence (P<0.01). This benefit remained significant in older patients and in patients with cores above 100cc. At 90 days, 147/460 patients (32 %) were deceased, with successful recanalization significantly associated with less frequent mortality (OR, 0.34; 95 %CI, 0.22–0.53; P<0.01). The rate of sICH was 17.4 % and did not differ significantly between groups. ConclusionsIn this large, pooled-cohort study of AIS-LVO patients with infarct cores over 50cc at baseline, we demonstrated that successful recanalization was associated with a better functional outcome, lower mortality, and similar rates of symptomatic intracranial hemorrhage for a wide spectrum of patients.

Hemorrhagic transformation in acute ischemic stroke: hemorrhagic subtypes and symptomatic intracranial hemorrhage

BackgroundFew clinical studies perform detailed analyses of subtypes of intracranial hemorrhage (ICH) after mechanical thrombectomy (MT) used to treat acute ischemic stroke. Symptomatic intracranial hemorrhage (sICH) is a formidable complication...