Intravenous Thrombolysis In Patients Research Articles

Predictive value of monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) for poor prognosis after intravenous thrombolytic therapy for acute ischaemic stroke

IntroductionThe purpose of this study was to examine the relationship between monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) and poor short-term 3-month and long-term 6-month prognosis after intravenous thrombolysis in patients with acute ischaemic stroke.Material and methodsBy retrospective analysis, 763 eligible patients with acute ischaemic stroke with intravenous thrombolysis were included in the study, and the general data and clinical laboratory examination results of the patients were collected. The relationship between MHR and poor prognosis at 3 and 6 months in patients with intravenous thrombolysis was derived by stepwise regression using the R language, followed by 1:1 propensity score matching to determine the MHR threshold and to investigate the relationship between high and low MHR values and poor prognosis.ResultsMHR level was found to predict the prognosis of intravenous thrombolysis patients with acute ischaemic stroke, and it was an effective predictor of poor prognosis at 3 and 6 months after intravenous thrombolysis. MHR has a threshold of 0.584. High MHR levels were strongly associated with a poor 3-month prognosis of intravenous thrombolysis in patients with acute ischaemic stroke (OR = 5.657; 95% CI: 4.124–7.762; p < 0.001). High MHR level was closely associated with poor prognosis of acute ischaemic stroke patients with intravenous thrombolysis at 6 months (OR = 4.923; 95% CI: 3.603–6.726; p < 0.001).ConclusionsMHR level is a valid predictor for poor prognosis at 3-6 months after intravenous thrombolysis in patients in acute ischaemic stroke.

Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study.

Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies. Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated. Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]). Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy. Fonds NutsOhra.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: A target trial analysis after the liberalization of institutional guidelines.

This study aimed to report the safety and efficacy of off-label intravenous thrombolysis (IVT) with alteplase after sequentially liberalizing our institutional guidelines allowing IVT for patients under direct oral anticoagulants (DOACs) regardless of plasma levels, time of last intake, and without prior anticoagulation reversal therapy. We utilized the target-trial methodology to emulate hypothetical criteria of a randomized controlled trial in our prospective stroke registry. Consecutive DOAC patients (06/2021-11/2023) otherwise qualifying for IVT were included. Safety and efficacy outcomes (symptomatic intracranial hemorrhage [ICH], any radiological ICH, major bleeding, 90-day mortality, 90-day good functional outcome [mRS 0-2 or return to baseline]) were assessed using inverse-probability-weighted regression-adjustment comparing patients with versus without IVT. Ninety eight patients fulfilled the target-trial criteria. IVT was given in 49/98 (50%) patients at a median of 178 (interquartile range 134-285) min after symptom onset with median DOAC plasma level of 77 ng/ml (15 patients had plasma levels > 100 ng/ml; 25/49 [51%] were treated within 12 h after last DOAC ingestion). Endovascular therapy was more frequent in patients without IVT (73% vs 33%). Symptomatic ICH occurred in 0/49 patients receiving IVT and 2/49 patients without IVT (adjusted difference -2.5%; 95% CI -5.9 to 0.8). The rates of any radiological ICH were comparable. Patients receiving IVT were more likely to have good functional outcomes. After liberalizing our approach for IVT regardless of recent DOAC intake, we did not experience any safety concerns. The association of IVT with better functional outcomes warrants prospective randomized controlled trials.

Acupuncture Extended the Thrombolysis Window by Suppressing Blood-Brain Barrier Disruption and Regulating Autophagy-Apoptosis Balance after Ischemic Stroke.

Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. The narrow therapeutic window (within 4.5 h) and severe hemorrhagic potential limits therapeutic efficacy of recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) acupuncture is an integral part of traditional Chinese medicine, specifically designed to address acute ischemic stroke by targeting key acupoints such as Shuigou (GV26) and Neiguan (PC6). In this study, we explored the therapeutic potential of XNKQ acupuncture in extending the time window for thrombolysis and interrogated the molecular mechanisms responsible for this effect. The effect of extending the thrombolysis window by acupuncture was evaluated via TTC staining, neuronal score evaluation, hemorrhagic transformation assay, and H&E staining. RNA sequencing (RNA-seq) technology was performed to identify the therapeutic targets and intervention mechanisms of acupuncture. Evans blue staining and transmission electron microscopy were used to assess blood-brain barrier (BBB) integrity. Immunofluorescence staining and co-immunoprecipitation were performed to evaluate the level of autophagy and apoptosis and validate their interactions with BBB endothelial cells. Acupuncture alleviated infarction and neurological deficits and extended the thrombolysis window to 6 h. The RNA-seq revealed 16 potential therapeutic predictors for acupuncture intervention, which related to suppressing inflammation and restoring the function of BBB and blood vessels. Furthermore, acupuncture suppressed BBB leakage and preserved tight junction protein expression. The protective effect was associated with regulation of the autophagy-apoptosis balance in BBB endothelial cells. Acupuncture intervention dissociated the Beclin1/Bcl-2 complex, thereby promoting autophagy and reducing apoptosis. XNKQ acupuncture could serve as an adjunctive therapy for rt-PA thrombolysis, aiming to extend the therapeutic time window and mitigate ischemia-reperfusion injury. Acupuncture suppressed BBB disruption by regulating the autophagy-apoptosis balance, which in turn extended the therapeutic window of rt-PA in IS. These findings provide a rationale for further exploration of acupuncture as a complementary candidate co-administered with rt-PA.

Endovascular thrombectomy with versus without intravenous thrombolysis in patients with acute basilar artery occlusion: a systematic review and meta-analysis.

The benefit and safety of intravenous thrombolysis before endovascular thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion (BAO) remains unclear. This article aims to investigate the clinical outcomes and safety of endovascular thrombectomy with versus without intravenous thrombolysis in acute BAO stroke patients. We conducted a comprehensive search of PubMed, Embase, Cochrane, and Web of Science databases to identify relevant literature pertaining to patients with acute BAO who underwent endovascular thrombectomy alone or intravenous thrombolysis bridging with endovascular thrombectomy (bridging therapy), until January 10, 2024. The primary outcome was functional independence, defined as a score of 0-2 on the modified Rankin Scale at 90days. The safety outcome was mortality at 90days and symptomatic intracranial hemorrhage within 48h. Effect sizes were computed as risk ratio (RR) with random-effect models. This study was registered in PROSPERO (CRD42023462293). A total of 528 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded. Finally, 2 RCTs and 10 cohort studies met the inclusion criteria. The findings revealed that the endovascular thrombectomy alone group had a lower rate of functional independence compared to the bridging therapy group (29% vs 38%; RR 0.78, 95% CI 0.68-0.88, p < 0.001), lower independent ambulation (39% vs 45%; RR 0.89, 95% CI 0.82-0.98, p = 0.01), and higher mortality (36% vs 28%, RR 1.22, 95% CI 1.08-1.37, p = 0.001). However, no differences were detected in symptomatic intracranial hemorrhage between the two groups (6% vs 4%; RR 1.12, 95% CI 0.74-1.71, p = 0.58). Intravenous thrombolysis plus endovascular thrombectomy seemed to led to better functional independence, independent ambulation, and lower risk of mortality without increasing the incidence of intracranial hemorrhage compared to endovascular thrombectomy alone. However, given the non-randomized nature of this study, further studies are needed to confirm these findings.

Nomogram prediction model for the risk of intracranial hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.

Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) might worsen the clinical outcomes, and a reliable predictive system is needed to identify the risk of hemorrhagic transformation after IVT. Retrospective collection of patients with acute cerebral infarction treated with intravenous thrombolysis in our hospital from 2018 to 2022. 197 patients were included in the research study. Multivariate logistic regression analysis was used to screen the factors in the predictive nomogram. The performance of nomogram was assessed on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots and decision curve analysis (DCA). A total of 197 patients were recruited, of whom 24 (12.1%) developed HT. In multivariate logistic regression model National Institute of Health Stroke Scale (NIHSS) (OR, 1.362; 95% CI, 1.161-1.652; p = 0.001), N-terminal pro-brain natriuretic peptide (NT-pro BNP) (OR, 1.012; 95% CI, 1.004-1.020; p = 0.003), neutrophil to lymphocyte ratio (NLR) (OR, 3.430; 95% CI, 2.082-6.262; p < 0.001), systolic blood pressure (SBP) (OR, 1.039; 95% CI, 1.009-1.075; p = 0.016) were the independent predictors of HT which were used to generate nomogram. The nomogram showed good discrimination due to AUC-ROC values. Calibration plot showed good calibration. DCA showed that nomogram is clinically useful. Nomogram consisting of NIHSS, NT-pro BNP, NLR, SBP scores predict the risk of HT in AIS patients treated with IVT.

Association between baseline hemoglobin level and early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke.

To investigate the association between baseline hemoglobin level and early neurologic deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS). Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation (CASE-Ⅱ, NCT04487340). Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy, and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis. A total of 8162 patients were included. Patients with END had lower baseline hemoglobin levels (136 and 140 g/L, P<0.01) and higher rates of anemia (24.2% and 16.9%, P<0.01) compared with non-END patients. Binary logistic regression analysis showed that baseline hemoglobin level (OR=0.995, 95%CI: 0.991-0.999, P<0.05) and anemia (OR=1.238, 95%CI: 1.055-1.454, P<0.01) were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients. Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients (P<0.01), although this relationship was only significant in male patients (P<0.05) and not in female patients (P>0.05). There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis, especially in male patients, in whom both lower and higher hemoglobin level may increase the risk of END.

Value of intravenous alteplase before thrombectomy among patients with tandem lesions and emergent carotid artery stenting: A subgroup analysis of the SWIFT DIRECT trial.

The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting. SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes. Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05). No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.

Higher fibrinogen and neutrophil-to-lymphocyte ratio are associated with the early poor response to intravenous thrombolysis in acute ischemic stroke.

Inflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear. AIS patients undergoing intravenous thrombolysis were enrolled between January 2018 and May 2023. Blood cell counts were sampled before thrombolysis. A good response was defined as a National Institutes of Health Stroke Scale (NIHSS) score decreased ≥4 or complete recovery 24 h after thrombolysis treatment. A poor response was defined as any increase in the NIHSS score or a decrease in the NIHSS score <4 at the 24 h after thrombolysis treatment compared with that at admission. Logistic regression analysis was performed to explore the relationship of the fibrinogen level and NLR with a poor thrombolysis response. Receiver operating characteristic (ROC) analysis was used to assess the ability of the fibrinogen level and NLR to discriminate poor responders. Among 700 recruited patients, 268 (38.29%) were diagnosed with a good response, and 432 (61.71%) were diagnosed with a poor response to intravenous thrombolysis. A binary logistic regression model indicated that an elevated fibrinogen level (odds ratio [OR], 1.693; 95% confidence interval [CI] 1.325-2.122, P < 0.001) and NLR (OR, 1.253; 95% CI, 1.210-2.005, P = 0.001) were independent factors for a poor response. The area under the curve (AUC) values for the fibrinogen level, NLR and fibrinogen level combined with the NLR for a poor response were 0.708, 0.605, and 0.728, respectively. Our research indicates that the levels of fibrinogen and NLR at admission can be used as a prognostic factor to predict early poor response to intravenous thrombolysis.

Dual antiplatelet therapy after intravenous thrombolysis for patients with minor ischemic stroke：A meta-analysis

ObjectiveIntravenous thrombolysis (IVT) has been shown to effectively decrease both the disability rate and mortality associated with acute ischemic stroke, however, there is also a risk of vascular re-occlusion. Antiplatelet therapy can mitigate this risk. Nevertheless, there are no relevant guidelines recommending whether the administration of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel can be performed following thrombolysis. The aim of this study was to conduct a meta-analysis utilizing multiple studies in order to assess the effectiveness and safety of DAPT after IVT in cases of acute mild ischemic stroke (AMIS). MethodsA comprehensive search on English literature published was performed on databases including PubMed, Embase, Web of Science, and Cochrane up until September 1, 2023. All cases were ischemic stroke patients who underwent IVT within a 4.5-hour timeframe and had a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 (or 3) upon admission. The primary efficacy endpoint is the 90-day Modified Rankin Scale (mRS) Score (MRS score 0–1), while the primary safety endpoint encompassed the occurrence of symptomatic intracranial hemorrhage (SICH) and 90-day mortality. The study's secondary objective is the recurrence of any type of stroke (hemorrhagic and ischemic) within a 90-day period. The included studies underwent an evaluation of bias risk using the Newcastle Ottawa scale. Risk ratios (RRs) and CIs were calculated using a random effects model, and the findings and heterogeneity among the included studies were visually presented on a forest plot. (There was a protocol registration (PROSPERO):). ResultsOut of the 1081 studies that were obtained, only 3 met the criteria and were included in the meta-analysis (657 patients in total). The findings indicate that, there was a significant difference in the mRS of 0–1 between single antiplatelet therapy (SAPT) with only aspirin or clopidogrel and DAPT with aspirin and clopidogrel ((RR,1.11[95%CI,0.99–1.24];P=0.07;I2=55%), and no significant difference in stroke recurrence after 90 days or 1 year ((RR,0.94[95%CI,0.41–2.16];P=0.89;I2=30%); Regarding safety evaluation, the results showed no significant difference in the SICH (RR,0.65[95%CI,0.11–3.97];P=0.64;I2=0%) and the incidence of mortality (RR,0.97[95%CI,0.19–4.96];P=0.97;I2=0%) between the two groups. ConclusionsFor patients with acute mild ischemic stroke (AMIS), in conjunction with DAPT after IVT can improve the 90-day prognosis, without increasing the risk of intracranial hemorrhage and 90-day mortality. However, it cannot reduce the risk of stroke recurrence.

Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke.

This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke. A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044). This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Intravenous Thrombolysis in Posterior versus Anterior Circulation Stroke: Clinical Outcome Differs Only in Patients with Large Vessel Occlusion.

The safety and efficacy of intravenous thrombolysis (IVT) are well established in anterior circulation stroke (ACS) but are much less clear for posterior circulation stroke (PCS). The aim of this study was to evaluate the occurrence of parenchymal hematoma (PH) and 3-month clinical outcomes after IVT in PCS and ACS. In an observational, cohort multicenter study, we analyzed data from ischemic stroke patients treated with IVT prospectively collected in the SITS (Safe Implementation of Treatments in Stroke) registry in the Czech Republic between 2004 and 2018. Out of 10,211 patients, 1166 (11.4%) had PCS, and 9045 (88.6%) ACS. PH was less frequent in PCS versus ACS patients: 3.6 vs. 5.9%, odds ratio (OR) = 0.594 in the whole set, 4.4 vs. 7.8%, OR = 0.543 in those with large vessel occlusion (LVO), and 2.2 vs. 4.7%, OR = 0.463 in those without LVO. At 3 months, PCS patients compared with ACS patients achieved more frequently excellent clinical outcomes (modified Rankin scale [mRS] 0-1: 55.5 vs. 47.6%, OR = 1.371 in the whole set and 49.2 vs. 37.6%, OR = 1.307 in those with LVO), good clinical outcomes (mRS 0-2: 69.9 vs. 62.8%, OR = 1.377 in the whole set and 64.5 vs. 50.5%, OR = 1.279 in those with LVO), and had lower mortality (12.4 vs. 16.6%, OR = 0.716 in the whole set and 18.4 vs. 25.5%, OR = 0.723 in those with LVO) (p < 0.05 in all cases). In PCS versus ACS patients, an extensive analysis showed a lower risk of PH both in patients with and without LVO, more frequent excellent and good clinical outcomes, and lower mortality 3 months after IVT in patients with LVO.

Abstract WMP11: Intravenous Thrombolysis in Patients Without versus With Visible Occlusion: A Secondary Analysis From the AcT Trial

Background: Around 70% of patients who present with acute ischemic stroke(AIS) have no visible occlusion on baseline imaging. In this post-hoc analysis from the AcT trial, we aimed to assess if there is a difference in safety/efficacy of intravenous thrombolysis in patients presenting with AIS symptoms with no visible occlusion(NVO) versus with visible occlusion(VO). We further sought to determine if this effect differed between tenecteplase and alteplase in the NVO group. Methods: Primary outcome was symptomatic intracerebral hemorrhage(SICH) within 24 hours. Secondary outcomes included modified Rankin Scale(mRS) 0-1, mRS 0-2, ordinal mRS at 90-120 days, and hemorrhage on imaging as defined by Heidelberg bleeding classification. Mixed effects regression model with quasi Poisson link was used to estimate NVO effect while adjusting for age, sex, NIHSS, thrombolytic type, and onset to needle time. Findings: Of the 1577 patients, 1470(93.2%) patients who received thrombolysis within 4.5h and with available baseline CT angiogram were included in the study. Of these, 479 (30.4%; 247: tenecteplase and 232: alteplase) were in NVO and 991 (69.6%; 509: tenecteplase and 482: alteplase) were in VO group. Patients in NVO group were younger (median 71y vs 75y), with less severe strokes (median NIHSS 6 vs 12). Patients in NVO group had significantly lower rates of death as compared to VO group (8.1% vs 19.1%, adjusted risk ratio(adjRR)1.5, 95%CI:1.0-2.6). There was no difference in rates of SICH (2.3% vs 3.6%, adjRR 0.99, 95%CI:0.5-2.1) or rates of 90-d mRS 0-1 (43.3% vs 31.9%, adjRR 1.0, 95%CI:0.8-1.1). All safety and efficacy outcomes were similar between alteplase and tenecteplase in NVO group. Interpretation: Thrombolysis is just as safe in patients with AIS symptoms with NVO as compared to those with VO on baseline imaging. When thrombolysis is given, there is no difference in outcomes between these group by thrombolytic type.

Abstract WP16: Thrombolysis in Wake-Up Stroke Improves Outcomes, Reduces Cost, and Reverses ADC Lesions

Introduction: Trials using advanced imaging have shown a benefit from intravenous thrombolysis in patients with wake-up stroke, but real-world data is limited. This study presents data on outcomes in patients presenting with wake-up stroke at a comprehensive stroke center comparing those who received thrombolysis to those who did not. Methods: In February 2022, our institution implemented a wake-up stroke protocol utilizing emergent MRI-based evaluation for possible thrombolysis. The protocol combines clinical criteria (suspected ischemic stroke with disabling neurologic deficits; last known normal within 12 hours; time from symptom discovery to arrival within 4.5 hours) and imaging criteria (absence of proximal large vessel occlusion; FLAIR-DWI mismatch; signal intensity ratio &lt; 1.15 in those able to receive perfusion imaging). In this study, we compared discharge outcomes and hospital length of stay for patients with ischemic stroke selected for wake-up protocol with vs. without thrombolytic therapy. In addition, we assessed the proportion of patients with reversibility of diffusion restriction, defined as a decrease in infarct volume on ADC sequence between the pre-treatment to 24-hour post-treatment MRI. Results: Between February 2022 &amp; June 2023, there were 31 wake-up stroke activations (~2 per month). Median admission NIHSS was 6. 30% had medium or distal vessel occlusions. 71% of stroke activations had a final diagnosis of ischemic stroke; 32% of cases were eligible per protocol and treated with thrombolysis. Compared to patients diagnosed with ischemic stroke but not eligible for treatment, those treated with thrombolysis were more likely to be discharged home (70% vs. 17%, p = 0.02) and had a shorter hospital stay by ~1.5 days (mean LOS 3.6 days vs. 4.8 days; median LOS 3 days vs. 4.5 days; p &lt;0.01). ADC reversibility was demonstrated in ~30% of patients who underwent thrombolysis. Conclusions: Intravenous thrombolysis for patients presenting with wake-up stroke was feasible, improved outcomes, and reduced potential cost. It also demonstrated ADC reversibility in 30% of cases. Further steps are needed to increase availability of emergent MRI and optimize door to thrombolysis times in order to streamline access for potential treatment.

Abstract WP199: Outcomes Following Posterior Cerebral Artery Thrombolysis vs Medical Management in those with Atrial Fibrillation

Background: The benefits of endovascular thrombectomy (EVT) for posterior cerebral artery (PCA) occlusion remain controversial, but intravenous thrombolysis (IVT) has proven benefit across nearly all ischemic stroke types. We isolated a cohort of patients with likely embolic PCA occlusions (those with atrial fibrillation) and compared outcomes associated with IVT and EVT versus medical management (MM). Methods: The National Inpatient Sample (2015-2020) was retrospectively queried for patients with a primary diagnosis of a PCA occlusion (without a concomitant basilar occlusion, BAO) with a secondary diagnosis of atrial fibrillation. Descriptive statistics and propensity score matching for IVT with multivariable logistic regression were used to determine the odds of routine discharge, hospital length of stay, and death between those treated with IVT and EVT versus MM. Results: Of the 107,525 screened patients with a primary diagnosis of a PCA occlusion, 27730(25.7%) had a secondary diagnosis of atrial fibrillation, of whom 3010 underwent IVT. In a 1:1 matched cohort(n=3010 per group), patients treated with IVT had greater odds of discharge to home (adjusted OR 1.87,95% CI 1.22 to 2.87) with no difference in length of hospital stay (adjusted β 0.26, 95% -0.71 to 1.22) or in-hospital death (adjusted OR 0.81, 95% CI 0.27 to 2.47) as compared to patients treated with MM. These trends were preserved in a secondary analysis of unmatched patients in multi variable regression models, and no significant benefit of EVT for these outcomes (OR 1.75, 95%CI 0.62-4.93). Patterns were also similar when patients with a concomitant BAO were included (routine discharge adjusted OR for IVT: 1.57, 95% CI:1.03-2.38). Conclusion: Our findings show a potential real-world benefit for IVT in patients with a PCA occlusion secondary to presumed cardio embolism, but no significant advantage with EVT.

Abstract 25: Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis

Introduction: Intravenous thrombolysis (IVT) is efficacious treatment of acute ischemic stroke (AIS). However, certain circumstances associated with increased bleeding risk, such as recent direct oral anticoagulation (DOAC) intake limits its use. Nonetheless, emerging evidence has shown promising results in this patient group. We investigated the safety and efficacy of IVT in patients with AIS and recent DOAC use. Methods: We conducted systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use. Outcomes of interest were symptomatic intracranial hemorrhage (sICH), any ICH, serious systemic bleeding (SSB), and 90-day functional independence (mRS 0-2). Moreover, we calculated pooled odds ratios (OR) for each outcome using a random effect meta-analysis to compare the rates between the patients with DOAC and non-DOAC upon IVT. Ultimately, we completed a sensitivity analysis for idarucizumab, NIHSS, and the timing of DOAC administration. Results: Our meta-analysis included 14 studies with 247079 patients (3610 in DOAC and 243469 in non-DOAC). In the DOAC group, the rate of sICH was 3% (95%CI 3 - 4%), any ICH was 12% (95%CI 7 - 19%), SSB 0.7% (95%CI 0 - 1%), and 90-day mRS 0-2 was 57% (95%CI 43 - 70%). No difference in the rates of sICH (3.4vs.3.5%; OR=0.95; 95%CI 0.67 - 1.36), any ICH (17.7vs.17.3%; OR=1.23; 95%CI 0.61 - 2.48), SSB (0.7vs.0.6%; OR=1.27; 95%CI 0.79 - 2.02), and 90-day mRS 0-2 (46.4vs.56.8%; OR=1.21; 95%CI 0.400 - 3.67) was found between DOAC and non-DOAC groups. Subgroup analysis revealed no significant difference in the sICH rate between idaricuzumab and no idaricizumab administration prior to IVT [Figure 1]. Conclusions: Our analysis demonstrated no significant difference in functional independence and hemorrhagic complication rates in AIS patients treated with IVT with recent DOAC compared to the no-DOAC group. Further prospective randomized clinical trials are needed to shed more light on this topic.

Abstract TMP13: Prehospital Stroke Scales Are Non-Inferior to NIHSS in Prediction of Intravenous Thrombolysis Use in a Large Telestroke Network

Introduction: Recent studies report similar outcomes with antiplatelet drugs and intravenous thrombolysis (IVT) in patients with minor nondisabling ischemic stroke. These patients still meet emergent triage criteria and can increase the burden on stroke systems through prehospital stroke activation. Prehospital large vessel occlusion (LVO) scales can improve triage of LVO patients but have not been evaluated as tools to predict IVT administration. We sought to determine if common LVO scales can predict IVT use in a large academic telestroke practice. Methods: This retrospective study included all video telestroke consults performed in a large academic telestroke network from 2019-2020. Patients were excluded if they were on anticoagulation, presented beyond 4.5 hours from last known well, or family declined IVT due to goals of care. We recorded presenting NIHSS and IVT recommendations. NIHSS was used to calculate 7 LVO scales (RACE, G-FAST, FAST-ED, VAN, PASS, 3I-SS, and C-STAT). Scale performance was assessed by calculating area under curve (AUC) and compared to NIHSS total score using the DeLong test. Youden cutpoint was established for each scale and subsequently used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. Results: A total of 513 patients were included; 205/513 (40%) were recommended IVT. Median (IQR) NIHSS was 1 (0-3) in non-IVT patients and 6 (4-11) in IVT patients. The RACE and G-FAST scales were noninferior to the NIHSS in predicting IVT recommendation (Table 1). Conclusion: The RACE and G-FAST scales may be useful triage tools to identify patients needing emergent stroke evaluation for consideration of IVT.

Analysis of Clinical Characteristics and Influencing Factors of Early Neurological Deterioration in Patients With Mild Stroke by Intravenous Alteplase Therapy.

Thrombolysis treatment for patients with mild stroke is controversial. The aim of our study was to investigate the clinical characteristics and influencing factors of early neurological deterioration (END) in this group of patients. A retrospective analysis was performed on ischemic stroke patients with intravenous thrombolysis (IVT) in Wenzhou Central Hospital. Subgroup analyses were performed for the mild stroke group and nonmild stroke group, END group, and non-early neurological deterioration group in mild stroke patients, respectively. A total of 498 patients were included in this study. Compared with the control group, the mild stroke group was younger age, less atrial fibrillation, previous history of stroke and less use of antithrombotic drugs, more dyslipidemia, smoking, and drinking. Small artery occlusion type was more common in mild stroke, cardioembolism and stroke of undetermined etiology type were less. In the mild stroke group, the symptomatic intracerebral hemorrhage (sICH) rate was 2.54%, and the END rate was 16.1%. Predictors of END included systolic blood pressure, blood glucose, cardioembolism subtype, sICH, and large vessel occlusion. In END patients, the sICH rate was 10.53%, and 84.21% of cases started to worsen within 12 hours after IVT. There was no statistically significant difference in the time to exacerbation among different subtypes. The occurrence of mild stroke in young patients was largely related to unhealthy lifestyles. The incidence of END in mild stroke IVT patients was low, with most occurring within 12 hours of IVT. There were many risk factors for END: large vessel occlusion and hyperglycemia were independent risk factors for END after IVT. sICH was an important but rare risk factor for END.

Predictive value of serum MDA and 4-HNE levels on the occurrence of early neurological deterioration after intravenous thrombolysis with rt-PA IVT in patients with acute ischemic stroke

ObjectiveThis study investigated the predictive value of serum MDA and 4-HNE levels on early neurological deterioration (END) after recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. MethodsThis study analyzed 287 AIS patients with standard-dose rt-PA IVT. Clinical baseline and pathological data were recorded before rt-PA IVT, and neurologic deficit was assessed by NIHSS. AIS patients were classified into Non-END and END groups. Serum MDA and 4-HNE levels were determined by ELISA and their correlations with NIHSS scores were evaluated. AIS patients were allocated into groups with high and low MDA or 4-HNE expression, and post-IVT END incidence was compared. Independent risk indexes for post-IVT END and the predictive value of serum MDA+4-HNE levels on post-IVT END were assessed. ResultsSerum MDA and 4-HNE were higher in AIS patients with post-IVT END. NIHSS score showed a positive correlation with serum MDA and 4-HNE levels. MDA levels were positively correlated with 4-HNE levels in AIS patients. END after IVT was increased in AIS patients with high MDA/4-HNE expression. FBG, lymphocyte percentage, PLR, NIHSS score, serum MDA, and 4-HNE levels were independent risk factors for END after IVT. The diagnostic efficacy of MDA+4-HNE in assessing post-IVT END in AIS patients (sensitivity 92.00 %, specificity 82.70 %) was higher than MDA or 4-HNE alone. ConclusionSerum MDA and 4-HNE levels were higher in AIS patients with post-IVT END than in those with non-END, and MDA+4-HNE possessed a higher predictive value for post-IVT END in AIS patients.