Symptomatic Intracranial Hemorrhage Research Articles

Stroke thrombectomy in the elderly: A propensity score matched study on a nationwide real-world registry.

Data on safety and efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke in older patients are limited and controversial, and people aged 80 or older were under-represented in randomized trials. Our aim was to assess EVT effect for ischemic stroke patients aged ⩾80 at a nationwide level. The cohort included stroke patients undergoing EVT from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). Patients were a priori divided into younger and older groups (<80 vs ⩾80). Primary outcome was good functional outcome (modified Rankin scale, mRS, 0-2 at 90 days). Secondary outcomes were symptomatic intracranial hemorrhage (sICH), successful reperfusion, EVT abortion. Propensity score matching (PSM) was performed between age groups for baseline features, functional status, stroke severity and neuroradiological features. Logistic regression was implemented to test the weight of age group on the predefined outcomes. Overall, 5872 individuals (1:1 matching, n = 2936 aged ⩾80 vs n = 2936 < 80) were matched from 13,922 records. In ⩾80 group 34.1% had good functional outcome, vs 51.2% in <80 group (absolute difference = -17.1%, p < 0.001), with a 4.4% excess in EVT abortion. Age ⩾80 was a negative independent predictor of good functional outcome (aOR = 0.4, 95% CI = 0.3-0.5), but had no impact on sICH. Age ⩾80 years represents a consistent predictor of worse functional outcome, independently from successful reperfusion and sICH. Cost-effectiveness studies are needed for tailored and implement sustainable care, and research should focus on strategies to improve functional outcome in older age patient groups.

Safety and Efficacy of Thrombectomy in Vietnamese Stroke Patients Selected Through Perfusion Imaging With an Onset Time Between 6-24 Hours.

Introduction Recent trials have demonstrated the remarkable benefit of endovascular treatment (EVT) up to 24 hour in patients with large vessel occlusion (LVO) and target mismatch profiles; however, benefits of late-window EVT in Vietnamese population remain poorly understood. This study aims to evaluate the real-world outcomes of EVT in acute ischemic stroke (AIS) patients selected using perfusion imaging within the 6- to 24-hour window. Methods A prospective study of consecutive patients with anterior circulation LVO stroke who underwent EVT within 6 to 24 hours after last known well between August 2022 and March 2024. Patients were selected based on the DAWN/DEFUSE-3 criteria (Perfusion-RAPID, iSchemaView). The primary outcome was the proportion of patients with functional independence at 90 days (modified Rankin Scale score of 0-2). The secondary outcomes were successful reperfusion defined by thrombolysis in cerebral infarction (TICI) ≥2b on the final procedure, and subgroup analysis between good (Hypoperfusion intensity ratio (HIR) <0.4) and poor collaterals (HIR ≥ 0.4) groups. Safety outcomes were mortality rate and symptomatic intracranial hemorrhage (sICH). Results Of 122 enrolled patients, 68% met inclusion criteria of DEFUSE-3 trial, 61% met DAWN trial criteria. Mean age was 66 years, median baseline NIHSS was 13, median time from stroke onset to hospital arrival was 12.55 hours (9.50 - 16.48), and median infarct volume was 11.5 mL. The rate of functional independence at 90 days was 45.9%. Successful reperfusion (TICI score of ≥2b) was achieved by 83.6% of cases. The 90-day mortality rate was 10.7%, sICH was reported in 8 patients (6.6%). Patients with good collaterals had better functional outcome. Conclusions This real-world observational study suggests that late window EVT may be safe and effective in eligible Vietnamese patients selected based on perfusion imaging, thus supporting its practical use in this patient population. Hypoperfusion intensity ratio is a robust indicator of collateral status and could made it a valuable addition to stroke imaging work-up in clinical setting.

EXCELLENT Registry: A Prospective, Multicenter, Global Registry of Endovascular Stroke Treatment With the EMBOTRAP Device.

The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots. EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee. After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P<0.001), pointing to a potential preprocedure indicator of challenging clot. The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03685578.

Transradial versus transfemoral access for mechanical thrombectomy: A single institution experience.

There has been debate in the literature regarding the adoption of a "radial-first" approach for mechanical thrombectomy (MT) in acute ischemic stroke (AIS). Conflicting reports suggest that transradial access (TRA) may allow for shorter times to reperfusion while others conclude that long-term functional outcomes may favor transfemoral access (TFA). Here, we report a single-institution experience with the adoption of TRA as the primary route for acute stroke intervention. We retrospectively reviewed a single-institution database of patients undergoing MT for AIS from March 2020 to April 2023. This time period was selected to capture the change in clinical practice at our institution from TFA to TRA. Primary and secondary outcomes included technical success, procedural complications, and long-term functional outcomes. Patients were stratified into two cohorts from initial access. Cohorts were compared utilizing inferential statistics. A total of 192 consecutive cases were identified, with 80 in the TFA cohort and 112 in the TRA cohort. There was no difference in outcomes with respect to time from puncture to recanalization, rates of successful recanalization (TICI ≥ 2b), number of passes, rates of symptomatic intracranial hemorrhage (sICH), modified Rankin scale (mRS) at discharge and 90 days, and 90-day mortality (p ≥ 0.05, all). The TRA had a higher rate of access conversion (p < 0.001), while the TFA cohort had a higher rate of access site complications (p < 0.05).

Prolonged intracranial catheter dwell time exacerbates penumbral stress and worsens stroke thrombectomy outcomes

BackgroundThe duration of mechanical thrombectomy (MT) is a negative predictor of outcomes in acute ischemic stroke (AIS), yet the precise mechanisms are unclear. We investigated whether the placement of large-bore...

Tenecteplase thrombolytic therapy for acute ischaemic stroke in China: a real-world, multicentre, retrospective, controlled study

Background and aimsTenecteplase (TNK) offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase. We aim to investigate the real-world evidence regarding its safety and...

Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials.

The current European Stroke Organisation expedited recommendation on tenecteplase (TNK) for acute ischemic stroke (AIS) advocates that TNK 0.25 mg/kg can be used alternatively to alteplase (tissue plasminogen activator [TPA]) for AIS of <4.5 hours duration, based on a meta-analytical approach establishing noninferiority. Since the publication of these guidelines, 4 additional randomized controlled clinical trials (RCTs) have provided further insight. We conducted an updated systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of TNK 0.25 mg/kg compared with TPA for the treatment of AIS within 4.5 hours of onset. The primary outcome was defined as the excellent functional outcome at 3 months (modified Rankin Scale [mRS] score 0-1), whereas good functional outcome (mRS score 0-2), reduced disability at 3 months (≥1-point reduction across all mRS scores), symptomatic intracranial hemorrhage (sICH), and 3-month mortality were evaluated as secondary outcomes. Pooled estimates were calculated with random-effects model. A prespecified subgroup analysis was performed stratifying for TNK formulation, that is, original TNK vs biocopy: recombinant human TNK tissue-type plasminogen activator that is available in China and has a different production process. Eleven RCTs were included comprising a total of 3,788 patients treated with TNK vs 3,757 patients treated with TPA. TNK was associated with higher likelihood of excellent functional outcome (risk ratio [RR] 1.05, 95% CI 1.01-1.10; p = 0.012; I2 = 0%; risk difference 2.95%; 95% CI 0.76%-5.14%; p = 0.008; I2 = 0%) and reduced disability at 3 months (common odds ratio 1.10, 95% CI 1.01-1.19; p = 0.034; I2 = 0%) compared with TPA while good functional outcome (RR 1.03, 95% CI 0.99-1.07; p = 0.142; I2 = 28%) was similar between the groups. Regarding safety outcomes, similar rates of sICH (RR 1.12, 95% CI 0.83-1.53; p = 0.456; I2 = 0%) and 3-month mortality (RR 0.97, 95% CI 0.82-1.15; p = 0.727; I2 = 12%) were observed. When stratified for TNK regimen (original vs biocopy), statistical significance in achieving an excellent functional outcome at 3 months was retained for the original TNK (RR 1.05, 95% CI 1.00-1.10; p = 0.044; I2 = 0%). The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice.

Abstract 4120957: Endovascular Thrombectomy Versus Medical Management for Acute Ischemic Stroke with Large Infarct: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke due to large vessel occlusions. Despite the increasing evidence for EVT, its efficacy remains understudied in patients with acute ischemic stroke with large infarcts. Patients with large-volume ischemic strokes are excluded from major randomized controlled trials (RCTs) despite contributing up to 25% of all acute ischemic strokes. Aim: This study aimed to compare clinical outcomes with endovascular thrombectomy versus medical management in patients with acute ischemic stroke with large infarct. Methods: We conducted a systematic literature review on PubMed, Embase, Scopus and Cochrane Library from inception to 15th May 2024 for RCTs. The inverse-variance random-effects model was used to pool odds ratio (OR) and risk ratio (RR) with 95% confidence intervals. The statistical significance was set at p&lt;0.05. Results: 6 RCTs with 1887 patients (945: EVT and 942: medical management) were included. The mean age in both EVT and medical management groups was 70 ± 11.4 years. EVT was associated with a better modified Rankin Score (mRS) at 90 days [OR: 1.68; 95% CI: 1.38, 2.04; p&lt;0.00001], mRS at 90 days (0-2) [OR: 2.47; 95% CI: 1.87, 3.27; p&lt;0.00001], mRS at 90 days (0-3) [OR: 1.96; 95% CI: 1.56, 2.46; p&lt;0.00001], and early neurological improvement [RR: 2.35; 95% CI: 1.79, 3.10; p&lt;0.00001] compared to medical management. EVT was also associated with a higher risk of symptomatic intracranial hemorrhage [RR: 1.71; 95% CI: 1.09, 2.66; p=0.02]. The 90-day mortality [RR: 0.86; 95% CI: 0.72, 1.02; p=0.08] was comparable between the two groups. Conclusion: Patients with acute ischemic stroke with large infarct had superior functional outcomes with EVT as compared to medical management alone. However, EVT was associated with higher risks of symptomatic intracranial hemorrhage, with comparable 90-day mortality risk. Further large RCTs are warranted to evaluate the outcomes with EVT in acute ischemic stroke with large infarct.

NCOG-18. META-ANALYSIS OF DIRECT ENDOVASCULAR THROMBECTOMY VS BRIDGING THERAPY IN THE MANAGEMENT OF ACUTE ISCHEMIC STROKE WITH LARGE VESSEL OCCLUSION

Abstract Debates persist when using intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). This systematic review and meta-analysis synthesized evidence on outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), comparing bridging therapy (BT) with MT alone. METHOD We conducted searches of PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to July 2023 to identify pertinent clinical trials and observational studies. RESULT 76 studies, involving 37,658 patients, revealed no significant difference in 90-day functional independence between DEVT and BT. However, a trend favoring BT for achieving functional independence with a modified Rankin Scale (mRS) of 0–1 was observed, having Odds ratio (OR) of 0.75 (95% CI 0.66–0.86; p &amp;lt; 0.001). DEVT was associated with higher postprocedural mortality (OR 1.44;95% CI 1.25–1.65; p &amp;lt; 0.001), but a lower risk of symptomatic intracranial hemorrhage compared to BT (OR 0.855; 95% CI 0.621–1.177; p = 0.327). Successful recanalization rates favored BT, emphasizing the importance of individualized treatment decisions (OR 0.759; 95% CI 0.594–0.969; p = 0.027). Sensitivity analyses were conducted to identify key contributors to heterogeneity. CONCLUSION Our meta-analysis underscores the intricate equilibrium between functional efficacy and safety in the evaluation of DEVT and BT for ACS-LVO. Fundamentally, while BT appears more efficacious, concerns about safety arise due to the superior safety profile demonstrated by DEVT. Individualized treatment decisions are imperative, and further trials are warranted to enhance precision in clinical guidance.

Beyond conventional imaging: A systematic review and meta-analysis assessing the impact of computed tomography perfusion on ischemic stroke outcomes in the late window.

Non-contrast cranial computed tomography (NCCT) and CT angiogram (CTA) have become essential for endovascular treatment (EVT) in acute stroke. Patient selection may improve when CT perfusion (CTP) imaging is also added for patient selection. We aimed to analyze the effects of implementing CTP in acute ischemic stroke (AIS) patients' treatment to assess whether stroke outcomes differ in the late window. We searched the PubMed, Embase, and Web of Sciences databases to obtain articles related to CTA and CTP in EVT. Collected patient data were split into two groups: the CTP and control (NCCT + CTA) cohorts. Primary outcomes evaluated were modified Rankin Scale (mRS) scores, symptomatic intracranial hemorrhages (sICHs), mortality, and successful recanalization. There were 14 studies with 5809 total patients in the final analysis: 2602 received CTP and 3202 were in the control group. CTP/CTA patients showed significantly lower rates of 90-day stroke-related mortality (odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.60-0.87, p < 0.01) and significantly higher successful recanalization (OR = 1.42, 95% CI = 1.06-1.94, p < 0.01) compared with CTA-only patients. Analysis of other outcomes including functional independence (mRS = 0-2), critical times, and intracranial hemorrhages was non-significant (p > 0.05). The study highlights the usefulness of CTP-guided therapy as a supplementary tool in EVT selection in the late window. Although the addition of CTP resulted in lower mortality, the favorable outcomes did not improve. Further evidence is required to establish a clearer understanding of the potential advantages or limitations of incorporating CTP in stroke imaging.

Endovascular Treatment of Patients With Acute Ischemic Stroke With Tandem Lesions Presenting With Low Alberta Stroke Program Early Computed Tomography Score.

Recent trials confirmed the efficacy and safety of endovascular thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS); however, evidence in tandem lesions is limited. This study evaluates endovascular thrombectomy safety and efficacy in patients with acute large-vessel occlusion with tandem lesions, stratified by baseline ASPECTS. We conducted a retrospective analysis of data from 16 centers. Inclusion criteria included the following: age ≥18 years, anterior circulation tandem lesions, endovascular thrombectomy <24 hours of symptom onset, and ≥70% internal carotid artery stenosis/occlusion. Patients were categorized into low (0-5) and high (6-10) ASPECTS. Inverse probability of treatment weighting matching was used to balance the groups. Primary outcomes included the following: 90-day modified Rankin Scale (mRS) score 0 to 2 and symptomatic intracranial hemorrhage. Secondary outcomes included the following: ordinal mRS, mRS 0 to 3, modified Thrombolysis in Cerebral Infarction ≥2b and 2c-3, petechial hemorrhage, parenchymal hematoma (1/2), early neurologic improvement, and mortality. Of 691 patients, 44 had ASPECTS 0 to 5 and 505 had ASPECTS 6 to 10. Patients with low ASPECTS had lower odds of 90-day mRS 0 to 2 (adjusted odds ratio [OR], 0.48; P=0.036) and higher odds of symptomatic intracranial hemorrhage (adjusted OR, 3.78; P=0.014). Additional significant differences were found in mRS shift, mRS 0 to 3, parenchymal hematoma 2, and mortality. In interaction analysis, the association between low ASPECTS and functional outcome persisted only in the internal carotid artery occlusion subgroup, with no significant interaction indicating no reason to suppose a difference between the effect of both subgroups. Endovascular thrombectomy in patients with tandem lesions with low ASPECTS is associated with reduced odds of functional recovery and increased symptomatic intracranial hemorrhage risk, when compared with patients with high ASPECTS. However, 30% of patients with low ASPECTS achieved 90-day functional independence, suggesting potential benefit for a nonnegligible proportion of patients.

Stent Retriever AssIsted Lysis Technique with Tirofiban: A Potential Bailout Alternative to Angioplasty and Stenting.

Angioplasty and stent placement have been described as a bailout technique in individuals with failed thrombectomy. We aimed to investigate Stent retriever AssIsted Lysis (SAIL) with tirofiban before angioplasty and stent placement. Patients from 2 comprehensive stroke centers were reviewed (2020-2023). We included patients with failed thrombectomy and/or underlying intracranial stenosis who received SAIL with tirofiban before the intended angioplasty and stent placement. SAIL consisted of deploying a stent retriever through the occluding lesion to create a bypass channel and infuse 10 mL of tirofiban for 10 minutes either intra-arterially or IV. The stent retriever was re-sheathed before retrieval. The primary end points were successful reperfusion (expanded TICI 2b-3) and symptomatic intracerebral hemorrhage. Additional end points included 90-day mRS 0-2 and mortality. After a median of 3 (interquartile range, 2-4) passes, 44 patients received the SAIL bridging protocol with tirofiban, and later they were considered potential candidates for angioplasty and stent placement bailout (43.2%, intra-arterial SAIL). Post-SAIL successful reperfusion was obtained in 79.5%. A notable residual stenosis (>50%) after successful SAIL was observed in 45.7%. No significant differences were detected according to post-SAIL: successful reperfusion (intra-arterial SAIL, 80.0% versus IV-SAIL, 78.9%; P = .932), significant stenosis (33.3% versus 55.0%; P = .203), early symptomatic re-occlusion (0% versus 8.0%; P = .207), or symptomatic intracerebral hemorrhage (5.3% versus 8.0%; P = .721). Rescue angioplasty and stent placement were finally performed in 15 (34.1%) patients (intra-arterial SAIL 21.0% versus IV-SAIL 44%; P = .112). At 90 days, mRS 0-2 (intra-arterial SAIL 50.0% versus IV-SAIL 43.5%; P = .086) and mortality (26.3% versus 12.0%; P = .223) were also similar. In patients with stroke in which angioplasty and stent placement are considered, SAIL with tirofiban, either intra-arterial or IV, seems to safely induce sustained recanalization, offering a potential alternative to definitive angioplasty and stent placement.

Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.

Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a Stachybotrys microspora triprenyl phenol family member, may extend this therapeutic window. In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence). Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42-87) and 8 (6-21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34-85) and 8 (6-22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0-12.1) and 10.0 (3.7-12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0-5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1-13.8]) for placebo (P=0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score <3 (39/90) improved in 58.3% (14/24) of patients in JX10 Cohorts versus 26.7% (4/15) for placebo (odds ratio, 4.23 [95% CI, 0.99-18.07]). In JX10 Cohorts, a significantly higher proportion of patients had modified Rankin Scale scores of 0 to 1 on day 90 (secondary end point) versus placebo (JX10: 21/52, 40.4% versus placebo: 7/38, 18.4%; P=0.03). JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent. URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786.

Care Quality and Outcomes of Ischemic Stroke in Patients With Premorbid Dementia: Get With The Guidelines-Stroke Registry.

Patients with premorbid dementia have been generally excluded from trials of stroke therapies, and their dementia diagnosis may affect the care received. There are few data on the quality of stroke care and outcomes in these patients. We compared the quality of care and outcomes for acute ischemic stroke patients with versus without premorbid dementia using national data from the Get With The Guidelines-Stroke registry between July 1, 2020, and December 31, 2021. Process outcomes included receiving intravenous thrombolysis, endovascular thrombectomy, and additional national quality measures. Clinical outcomes included ambulatory status at discharge, discharge destination, and mortality. The analyses were adjusted for patient and hospital characteristics. Among 609 350 patients with acute ischemic stroke, 29 751 of 546 407 (5.4%) had documented prestroke dementia (median age, 84 [interquartile range, 78-89]; 62.8% female). Patients with versus without premorbid dementia were more likely to arrive via emergency medical services (70.5% versus 46.8%) and had more severe strokes (median National Institutes of Health Stroke Scale score, 7 [interquartile range, 3-15] versus 3 [interquartile range, 1-8]). They were less likely to be admitted to a comprehensive stroke center (17.9% versus 22.7%; P<0.0001), to receive intravenous thrombolysis (9.6% versus 11.1%; adjusted odds ratio [aOR], 0.91 [95% CI, 0.87-0.95]) or endovascular thrombectomy (4.5% versus 7.4%; aOR, 0.62 [95% CI, 0.56-0.68]), attain each of the Get With The Guidelines-Stroke Achievement Measures and Quality Measures, or attain defect-free stroke care (92.0% versus 95.0%; aOR, 0.75 [95% CI, 0.71-0.78]). Patients with premorbid dementia had longer door-to-needle times (adjusted difference, 3.17 minutes [95% CI, 1.34-5.01]), lower odds of being discharged home (43.8% versus 60.1%; aOR, 0.96 [95% CI, 0.93-1.00]), and higher odds of being nonambulatory at discharge (25.8% versus 9.3%; aOR, 1.62 [95% CI, 1.54-1.69]), and of in-hospital mortality or hospice admission (23.3% versus 8.6%; aOR, 1.38 [95% CI, 1.32-1.43]). Symptomatic intracranial hemorrhage after intravenous thrombolysis/endovascular thrombectomy did not differ (5.3% versus 3.7%; aOR, 1.13 [95% CI, 0.97-1.31]). Patients with premorbid dementia experienced slightly poorer quality of stroke care across multiple measures, were less likely to receive acute stroke interventions, and had worse poststroke outcomes than patients without dementia in a large nationwide registry. Our findings underscore the need for concerted efforts to further improve care quality and outcomes in this population.

Advancing stroke safety and efficacy through early tirofiban administration after intravenous thrombolysis: The multicenter, randomized, placebo-controlled, double-blind ASSET IT trial protocol.

Intravenous thrombolysis (IVT) is the cornerstone treatment for the acute ischemic stroke (AIS) within 4.5 h after onset. Current guidelines recommend administering antiplatelet medications 24 h after IVT. However, vascular reocclusion is a common occurrence after IVT. Tirofiban, a platelet glycoprotein IIb/IIIa antagonist, can help deter macrovascular reocclusion, prevent microvascular thrombosis, and enhance cerebral blood flow. This trial aims to assess whether early administration of tirofiban can improve clinical outcomes in patients with AIS who received IVT. The Advancing Stroke Safety and Efficacy through Early Tirofiban Administration after Intravenous Thrombolysis (ASSET IT) Trial is an investigator-initiated, randomized, placebo-controlled, double-blind, multicenter study. Up to 832 eligible patients will be consecutively randomized in a 1:1 ratio to receive either intravenous tirofiban or placebo over a period of 2 years across 38 stroke centers in China. The primary endpoint is excellent functional status at day 90, defined as a modified Rankin Score of 0-1. Primary safety endpoints include symptomatic intracerebral hemorrhage at 24 h and mortality at 90 days. NCT06134622 (clinicaltrials.gov).

Efficacy and safety of tirofiban plus recombinant tissue plasminogen activator versus recombinant tissue plasminogen activator alone in acute ischemic stroke patients: a meta-analysis

ObjectiveTirofiban plus recombinant tissue plasminogen activator (rtPA) shows good efficacy and safety in treating acute ischemic stroke (AIS) patients, but there is a lack of comprehensive assessment. This meta-analysis aimed to compare the efficacy and safety of rtPA plus tirofiban with rtPA alone in AIS patients. MethodsThis meta-analysis retrieved studies comparing rtPA intravenous thrombolysis followed by tirofiban (rtPA+T group) versus rtPA intravenous thrombolysis alone (rtPA group) for AIS patients in Excerpt Medica Database, Web of Science, Cochrane, PubMed, China National Knowledge Infrastructure, Wanfang, and SinoMed until March 2024. ResultsTwenty studies with 2048 AIS patients were enrolled in this meta-analysis. National Institute of Health stroke scale (NIHSS) score after treatment was lower in the rtPA+T group than the rtPA group [standardized mean differences (SMD)=-1.41; 95 % confidence interval (CI)=-1.83, -0.98; P<0.001]. The proportion of AIS patients achieving a favorable functional outcome (modified Rankin Scale score ≤2) was increased in the rtPA+T group versus the rtPA group [relative risk (RR)=1.13; 95 % CI=1.05, 1.21; P=0.001]. The incidence of re-occlusion was lower in the rtPA+T group than in the rtPA group (RR=0.24; 95 % CI=0.10, 0.59; P=0.002), but the incidence of intracranial hemorrhage (ICH) (RR=0.85; 95 % CI=0.51, 1.43), symptomatic ICH (RR=1.10; 95 % CI=0.43, 2.84), and mortality (RR=1.39; 95 % CI=0.53, 3.65) was not different between the two groups (all P>0.05). The stability assessed by sensitivity analysis was good, and no publication bias was found. ConclusionrtPA plus tirofiban achieves superior efficacy with comparable safety profiles compared to rtPA alone in AIS patients.

Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887-894.

Clinical application of the modified Pullicino formula in endovascular thrombectomy in acute anterior circulation large cerebral infarction-A two-center retrospective study.

This study aimed to assess whether the modified Pullicino formula could be used as a screening indicator for measuring infarct volume before endovascular thrombectomy (EVT) and observe baseline factors affecting neurological recovery in patients with acute anterior circulation large-core cerebral infarction. The Pullicino formula × (1-22%) was applied to anterior circulation large cerebral infarctions with ASPECTS <6 to screen patients with infarct volumes of 70-150 mL. The outcomes were assessed by mRS score at 90 days, modified Treatment in Cerebral Ischemia (mTICI) score, symptomatic intracranial hemorrhage within 48 h, and death rate within 90 days. Significantly more patients in the EVT group with infarct volumes 70-150 mL had mRS ≤3 at 90 days than did the standard drug therapy (OR, 2.93; 95% CI, 1.08-7.89, p=0.03) and a significantly decreased mortality rate (OR, 0.36; 95% CI, 0.13-0.98; p=0.04), with 88.2% in patients with mTICI ≥2b. There was no significant difference in the intracranial hemorrhage. EVT (adjusted OR [aOR], 2.84; 95% CI, 1.15-7.01, p=0.02), infarct volume <150 mL (aOR, 3.47; 95% CI, 1.20-10.14, p=0.02), and intracranial atherosclerosis (aOR, 4.20; 95% CI, 1.24-14.04, p=0.02) were significantly associated with patient prognosis. Without commercial artificial intelligence software, the modified Pullicino formula can be used to calculate infarct volume and, in combination with ASPECTS <6, to select patients who may benefit from EVT.

Clinical Observation of Infarct Volume ≥150mL in Endovascular Thrombectomy Treatment.

Whether patients with infarct volume ≥150mL could benefit from endovascular thrombectomy (EVT) remains unclear. Patients (n=104) with anterior circulation Alberta Stroke Program Early Computed Tomography Score <6 were screened for infarct volume ≥150mL using the Pullicino formula × (1-22%). The following were compared with the baseline at 90 days: the modified Rankin scale score (mRS) ≤3, mortality rate, symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours, and modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b between the EVT and drug therapy (DT) groups. In patients with infarct volumes ≥150mL, mRS≤3 at 90 days was higher in the EVT group than in the DT group [adjusted odds risk (aOR), 5.52; 95% CI: 1.10-28.24, P =0.04), and mTICI ≥2b at 82.8%. Intracranial hemorrhage within 48 hours occurred in 7 (24.1%) patients in the EVT group and 5 (14.7%) in the DT group (aOR, 0.75; 95% CI: 0.16-3.46; P =0.71). Older age (aOR, 0.94; 95% CI: 0.90-0.99, P =0.01), EVT treatment (aOR, 4.51; 95% CI: 1.60-12.78, P =0.01), and infarct volume ≥150mL (aOR, 0.11; 95% CI: 0.04-0.31, P <0.01) were significantly associated with patient prognosis. Patients with infarct volume ≥150mL who received EVT had a higher proportion of mRS≤3 compared with those who received DT. However, there was no statistically significant difference in intracranial hemorrhage and death between the groups. EVT, smaller infarct volume, and younger age were associated with a good prognosis. The findings require large sample data verification.

Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial

Tenecteplase has potential benefits over alteplase, the standard agent for intravenous thrombolysis in acute ischaemic stroke, because it is administered as a single bolus and might have superior efficacy. The ATTEST-2 trial investigated whether tenecteplase was non-inferior or superior to alteplase within 4·5 h of onset. We undertook a prospective, randomised, parallel-group, open-label trial with masked endpoint evaluation in 39 UK stroke centres. Previously independent adults with acute ischaemic stroke, eligible for intravenous thrombolysis less than 4·5 h from last known well, were randomly assigned 1:1 to receive intravenous alteplase 0·9 mg/kg or tenecteplase 0·25 mg/kg, by use of a telephone-based interactive voice response system. The primary endpoint was the distribution of the day 90 modified Rankin Scale (mRS) score and was analysed using ordinal logistic regression in the modified intention-to-treat population. We tested the primary outcome for non-inferiority (odds ratio for tenecteplase vs alteplase non-inferiority limit of 0·75), and for superiority if non-inferiority was confirmed. Safety outcomes were mortality, symptomatic intracranial haemorrhage, radiological intracranial haemorrhage, and major extracranial bleeding. The trial was prospectively registered on ClinicalTrials.gov (NCT02814409). Between Jan 25, 2017, and May 30, 2023, 1858 patients were randomly assigned to a treatment group, of whom 1777 received thrombolytic treatment and were included in the modified intention-to-treat population (n=885 allocated tenecteplase and n=892 allocated alteplase). The mean age of participants was 70·4 (SD 12·9) years and median National Institutes of Health Stroke Scale was 7 (IQR 5-13) at baseline. Tenecteplase was non-inferior to alteplase for mRS score distribution at 90 days, but was not superior (odds ratio 1·07; 95% CI 0·90-1·27; p value for non-inferiority<0·0001; p=0·43 for superiority). 68 (8%) patients in the tenecteplase group compared with 75 (8%) patients in the alteplase group died, symptomatic intracerebral haemorrhage (defined by SITS-MOST criteria) occurred in 20 (2%) versus 15 (2%) patients, parenchymal haematoma type 2 occurred in 37 (4%) versus 26 (3%) patients, post-treatment intracranial bleed occurred in 94 (11%) versus 78 (9%) patients, significant extracranial haemorrhage occurred in 13 (1%) versus six (1%) patients, respectively, and angioedema occurred in six (1%) participants in both groups. Tenecteplase 0·25 mg/kg was non-inferior to 0·9 mg/kg alteplase within 4·5 h of symptom onset in acute ischaemic stroke. Easier administration of tenecteplase, especially in the context of interhospital transfers, indicates that tenecteplase should be preferred to alteplase for thrombolysis in acute ischaemic stroke. The ATTEST-2 population was large and representative of thrombolysis-eligible patients in the UK and, together with findings from other trials, provides robust evidence supporting the introduction of tenecteplase in preference to alteplase. The Stroke Association and British Heart Foundation.