Intravenous Thrombolysis Group Research Articles

Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT. We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch. Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P=0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P=0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P<0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion (Pall interaction<0.05). Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone. URL: https://clinicaltrials.gov; Unique identifier: NCT04487340.

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.

Remote Ischemic Conditioning With Medical Management or Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date. We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073). There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, p = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group (p < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group. In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.

Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis.

Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively (P=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (P=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903.

Impact of Early Mobilization on Patients With Acute Ischemic Stroke Treated With Thrombolysis or Thrombectomy: A Randomized Controlled Trial

Background Early mobilization (EM) within 24 to 72 hours post-stroke may improve patients’ performance and ability. However, after intravenous thrombolysis (IVT) or mechanical thrombectomy (MT), the increased risk of hemorrhagic complications impacts the implementation of early out-of-bed mobilization. Few studies have investigated EM after IVT or MT for acute ischemic stroke (AIS), and its impact in these patients is unknown. Objective To investigate the effect of EM on AIS treated with IVT or MT.| Methods We recruited 122 patients with first AIS; 60 patients were treated with IVT, and 62 patients were treated with MT. For each IVT and MT cohort, the control groups received standard early rehabilitation, and the intervention groups received an EM protocol. The training lasted 30 minutes/day, 5 days/week until discharge. Main Outcomes Measures The effectiveness of the interventions was evaluated using the motor domain of the Functional Independence Measure (FIM-motor) and the Postural Assessment Scale for Stroke Patients (PASS) at baseline, 2-week, 4-week, and 3-month post-stroke, the Functional Ambulation Category 2-week post-stroke, and the total length of stay at the stroke center. Results Both IVT and MT treatment groups showed improved FIM-motor and PASS scores over time; however, only the IVT EM group had significantly improved FIM-motor performance within 1 month after stroke than the control group. Conclusion. An EM protocol with the same intervention time and session frequency per day as in the standard care protocol was effective in improving the functional ability of stroke patients after IVT.

Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke

The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy. To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset. Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313). Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone. The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes. In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.

Abstract TP278: Identifying High-Risk Patients With Poor Prognosis in Acute Phase of Ischemic Stroke: Treatment-Specific Risk Scales Developed From the National Neurological Medical Center of China

Background: There is still a lack of acute ischemic stroke (AIS) prognostic prediction scales to assist in more scientific and efficient clinical management of patients. Objective: Real-world data were utilized to construct and validate an easily popularized prediction score for poor prognosis in the acute phase of AIS so as to provide a basis for clinical monitoring and intervention of specific indicators. Method: Patients discharged from Huashan Hospital, Fudan University between 2015 and 2021 were consecutively included. AIS with premorbid mRS ≤ 2 within 72 hours of onset was included. Patients treated with arterial thrombectomy were excluded. Subjects were divided into "intravenous thrombolysis group" and "non-intravenous thrombolysis group". Based on the data of discharge patients from 2015 to 2020 (Model Training Set), logistic regression model with restricted cubic splines were applied to construct the "prognostic scale of AIS acute stage based on treatment stratification, PAIST Scale". Performance of the scale was tested using the area under the receiver operating characteristic curve (AUC-ROC) based on data from patients discharged in 2021 (External Validation Set). Result: A total of 1971 patients (437 thrombolysis) were included. The "PAIST Scale" of the thrombolysis patients included: Baseline NIHSS (5-15 = 11, ≥ 16 = 20), deep vein thrombosis (yes = 5), Neuron specific enolase (&gt; 13 ng/ml = 3), and neutrophil percentage (&gt; 70% = 5). The "PAIST Scale" of the Non-thrombolytic population: Baseline NIHSS (5-15 = 12, ≥ 16 = 20), deep venous thrombosis (yes = 4), Neuron specific enolase (&gt; 12.5 ng/ml = 1), neutrophil percentage (&gt; 66% = 3), age (&gt; 64y = 2), fasting blood glucose (&gt; 5.8 mmol/l = 2), serum potassium (&lt; 3.8 mmol/L = 1). In the external validation set, the AUC-ROC values of "PAIST Scale" were 0.855 in the non-thrombolysis group and 0.778 in the thrombolysis group. Meanwhile, patients defined as high-risk by the "PAIST scale" had an actual incidence of poor prognosis of 76.92% in the thrombolysis group (&gt; 19 points) and 61.11% in the non-thrombolysis group (&gt; 17 points). Conclusion: The "PAIST Scale" established in this study can effectively identify patients at high risk of poor prognosis in the acute phase among patients with mild to moderate stroke.

Thrombectomy versus combined thrombolysis and thrombectomy in patients with large vessel occlusion and chronic kidney disease

BackgroundWhether intravenous thrombolysis (IVT) should be bridged before mechanical thrombectomy (MT) remains uncertain in patients with large vessel occlusion (LVO) and chronic kidney disease (CKD). MethodsThis research systematically enrolled every patient with both acute ischemic stroke (AIS) and CKD who received MT and fulfilled the criteria for IVT from January 2015 to December 2022. According to whether they underwent IVT, the patients were categorized into two cohorts: MT and combined IVT + MT. A binary logistic regression model was used to adjust for potential confounders, and propensity score matching analysis was used to assess the efficacy and safety of IVT in AIS patients with CKD who underwent MT. ResultsA total number of 406 patients were ultimately included in this study, with 236 patients in the MT group and 170 in the combined group. After PSM, there were 170 patients in the MT group and 170 in the combined group, and the clinical characteristics between the two groups were well balanced. The MT + IVT group had better long-term functional outcomes than the MT group (35.9% versus 21.2%, P = 0.003) and more modified thrombolysis in cerebral infarction (mTICI) (2b-3) (94.1% versus 87.6%, P = 0.038), while no significant difference was found regarding symptomatic intracranial hemorrhage (sICH). In line with the results observed in the in the postmatched population, the logistic regression revealed that patients in the IVT + MT group demonstrated superior clinical outcomes (adjusted OR 0.440 [95% CI (0.267–0.726)], P = 0.001) in the prematched population. ConclusionFor LVO patients with CKD and indications for IVT, IVT bridging MT improves their prognosis compared with direct MT.

Intravenous Thrombolysis Before Endovascular Treatment in Posterior Circulation Occlusions: A MR CLEAN Registry Study.

The effectiveness of intravenous thrombolysis (IVT) before endovascular treatment (EVT) has been investigated in randomized trials and meta-analyses. These studies mainly concerned anterior circulation occlusions. We aimed to investigate clinical, technical, and safety outcomes of IVT before EVT in posterior circulation occlusions in a nationwide registry. Patients were included from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), a nationwide, prospective, multicenter registry of patients with acute ischemic stroke due to a large intracranial vessel occlusion receiving EVT between 2014 and 2019. All patients with a posterior circulation occlusion were included. Primary outcome was a shift toward better functional outcome on the modified Rankin Scale at 90 days. Secondary outcomes were favorable functional outcome (modified Rankin Scale scores, 0-3), occurrence of symptomatic intracranial hemorrhages, successful reperfusion (extended Thrombolysis in Cerebral Ischemia ≥2B), first-attempt successful reperfusion, and mortality at 90 days. Regression analyses with adjustments based on univariable analyses and literature were applied. A total of 248 patients were included, who received either IVT (n=125) or no IVT (n=123) before EVT. Results show no differences in a shift on the modified Rankin Scale (adjusted common odds ratio, 1.04 [95% CI, 0.61-1.76]). Although symptomatic intracranial hemorrhages occurred more often in the IVT group (4.8% versus 2.4%), regression analysis did not show a significant difference (adjusted odds ratio, 1.65 [95% CI, 0.33-8.35]). Successful reperfusion, favorable functional outcome, first-attempt successful reperfusion, and mortality did not differ between patients treated with and without IVT. We found no significant differences in clinical, technical, and safety outcomes between patients with a large vessel occlusion in the posterior circulation treated with or without IVT before EVT. Our results are in line with the literature on the anterior circulation.

Long-term outcomes of intravenous fibrinolysis in central retinal artery occlusion

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that can lead to irreversible loss of vision. Intravenous thrombolysis (IVT) has been used experimentally for its treatment. Our study aimed to evaluate the effect of emergency IVT on CRAO and its impact on visual acuity outcomes. We conducted a retrospective observational study of patients with CRAO. A total of 46 patients with CRAO were analysed; 16 patients received IVT treatment (IVT group) while 30 did not (no-IVT group). Seven patients from the IVT group received IVT early, within 4.5 hours (h) after the onset of symptoms (early-IVT), and 9 patients received it beyond this timeframe (late-IVT). The median time-to-hospital was 8.5 h: 3 h for the IVT group and 24 h for the no-IVT group. The median time-to-treatment was 5 h. The median outcome of visual acuity was 0.05 in the early-IVT, 0.025 in the late-IVT, and 0.01 in the no-IVT group. Among patients who received IVT early, 86% exhibited significant visual improvement. This improvement was four-fold greater compared to all other groups (p = 0.040), including the late-IVT (p = 0.011) and no-IVT groups (p = 0.023). No complications of the treatment were reported. Our study confirms that the administration of IVT treatment for CRAO within the 4.5-h time window is both safe and effective.

Outcomes of endovascular treatment alone or with intravenous alteplase in acute ischemic stroke Patients: A retrospective cohort study

ObjectiveThe aim of this study is to compare the clinical outcomes, safety, and workflow of patients who underwent endovascular treatment (EVT) alone or in combination with intravenous thrombolysis (IVT), against a control group who only received EVT. MethodsA retrospective analysis from May 2018 to September 2021 was conducted on 50 patients exhibiting acute ischemic stroke symptoms. 35 patients received EVT alone, while 15 received EVT and IVT. The data collected included demographic information, comorbid diseases, symptom onset time, duration from admission to puncture, and clinical outcomes via the National Institutes of Health Stroke Scale score and modified Rankin scale score at admission and 90 days post-procedure. ResultsNo significant differences were observed in the 90-day modified Rankin scale scores between the EVT + IVT and EVT alone groups (p > 0.05). NIHSS scores were also similar between the groups (p > 0.05). The EVT + IVT group demonstrated higher intracranial hemorrhage and symptomatic intracranial hemorrhage rates than the EVT alone group, but the difference became insignificant after adjusting for age and sex (p < 0.01). Mortality outcomes showed no significant difference (p > 0.05). ConclusionThe combined EVT and IVT treatment's safety outcomes are not inferior, aligning with existing literature.

Mechanical thrombectomy combined with intravenous thrombolysis for acute ischemic stroke: a systematic review and meta-analyses

To assess the clinical value of mechanical thrombectomy (MT) combined with intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) by comparing it with the MT alone. In this study, we conducted a comprehensive meta-analysis of both observational and randomized controlled studies (RCTs) to investigate various outcomes. Our search for relevant studies was conducted between January 2011 and June 2022 in four major databases: PubMed, Embase, WOS, and Cochrane Library. We collected data on several outcomes, including functional independence (FI; defined as modified Rankin Scale score of 0 to 2), excellent outcomes (mRS 0–1), successful recanalization (SR), symptomatic intracerebral hemorrhage (sICH), any intracerebral hemorrhage (aICH), and mortality at three months or discharge. The primary efficacy outcome and safety outcome were FI and sICH, respectively, whereas excellent outcomes and SR were considered secondary efficacy outcomes. Additionally, mortality and aICH were analyzed as secondary safety outcomes. We employed the Mantel–Haenszel fixed-effects model for RCTs when I2 < 50%, otherwise the random-effects model was utilized. For observational studies and subgroup analyses, we used the random-effects model to minimize potential bias. A total of 55 eligible studies (nine RCTs and 46 observational studies) were included. For RCTs, the MT + IVT group was superior in FI (OR: 1.27, 95% CI: 1.11–1.46), excellent outcomes (OR: 1.21, 95% CI: 1.03–1.43), SR (OR: 1.23, 95% CI: 1.05–1.45), mortality (OR: 0.72, 95% CI: 0.54–0.97) in crude analyses. In adjusted analyses, the MT + IVT group reduced the risk of mortality (OR: 0.65, 95% CI: 0.49–0.88). However, the difference in FI between the MT + IVT group and the MT alone group was not significant (OR: 1.17, 95% CI: 0.99–1.38, Fig. 3a). For observational studies, the results of FI (OR: 1.34, 95% CI: 1.16–1.33), excellent outcomes (OR: 1.30, 95% CI: 1.09–1.54), SR (OR: 1.23, 95% CI: 1.05–1.44), mortality (OR: 0.70, 95% CI: 0.64–0.77) in the MT + IVT group were better. Additionally, the MT + IVT group increased the risk of hemorrhagic transformation (HT) including sICH (OR: 1.16, 95% CI: 1.11–1.21) and aICH (OR: 1.24, 95% CI: 1.05–1.46) in crude analyses. In adjusted analyses, significant better outcomes were seen in the MT + IVT group on FI (OR: 1.36, 95% CI: 1.21–1.52), excellent outcomes (OR: 1.49, 95% CI: 1.26–1.75), and mortality (OR: 0.73, 95% CI: 0.56–0.94). The MT + IVT therapy did improve the prognosis for AIS patients and did not increase the risk of HT compared with MT alone therapy.

Intravenous Thrombolysis or Medical Management for Minor Strokes.

To evaluate the outcomes of acute ischemic stroke patients with minor deficits treated with either intravenous thrombolysis (IVT) or routine medical management (MM). The study included patients with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) scores of 5 or less who were treated with IVT within 4.5 hours from symptom onset and were classified as the IVT group. The MM group consisted of an equal number of patients with minor strokes, matched for sex, age, and severity, who did not receive thrombolysis. Data on patient information were collected for both groups. A total of 26,236 patients were included in this study (13,208 in IVT and 13,208 in MM). Of these patients, 67.9% were men, and the mean age was 67.1 years (standard deviation: 10.9). At 3 months, the IVT group had a higher rate of stroke-independent outcome (Rankin Scale score of 0-2) compared with the MM group (IVT vs. MM: 91.6 vs. 88.6%, absolute difference: 2.5%, 95% confidence interval [CI]: 1.6-3.4%, p = 0.008; adjusted hazard ratio [HR]: 1.2, 95% CI: 1.1-1.4, p = 0.003). Furthermore, there was no significant difference in 3-month mortality rates between the IVT and MM groups (IVT vs. MM: 2.1 vs. 2.5%, absolute difference: -0.6%, 95% CI: -1.1 to 0.3%, p = 0.11; adjusted HR: 0.9, 95% CI: 0.8-1.2, p = 0.09). Compared with MM, IVT does not reduce mortality in minor ischemic stroke but improves functional outcomes in minor stroke with an NIHSS score of 3 to 5.

Effect of intravenous thrombolysis on core growth rate in patients with acute cerebral infarction.

This study aimed to investigate the effects of recombinant tissue plasminogen activator intravenous thrombolysis (IVT) on the core growth rate of acute ischemic stroke. Stroke patients with large vessel occlusion and non-recanalization from IVT treatment were retrospectively included in this study and divided into two groups: IVT and non-IVT. The core growth rate was estimated by the acute core volume on perfusion CT divided by the last known well time from stroke to CT perfusion. The primary endpoint was the core growth rate, the tissue outcome was 24 h-ASPECTS, and the clinical outcome was a 3-month modified Rankin score. A total of 94 patients were included with 53 in the IVT group and 41 in the non-IVT group. There was no significant difference in age, gender, hypertension, diabetes, atrial fibrillation, acute NIHSS, and last known well time from stroke to CT perfusion acquisition between the two groups. The core growth rate in the IVT group was lower than that in the non-IVT group, which was statistically significant after multivariate adjustment (coefficient: -5.20, 95% CI= [-9.85, -0.56], p = 0.028). There was a significant interaction between the IVT and the collateral index in predicting the core growth rate. The analysis was then stratified according to the collateral index, and the results suggested that IVT reduced the core growth rate more significantly after the worsening of collateral circulation (coefficient: 15.38, 95% CI= [-26.25, -4.40], p = 0.007). The 3-month modified Rankin score and 24 h-ASPECTS were not statistically significant between the two groups. Intravenous thrombolysis reduces the core growth rate in patients with AIS, especially those with poor collateral status.

Abstract TMP2: Intravenous Thrombolysis For Ischemic Stroke With Unknown Time Of Onset: Differences Between Wake-up Stroke And Non-wake-up Subtypes: EOS

Background: The unknown onset stroke can be categorized into two groups; wake-up stroke (WUS) and non-wake-up unwitnessed stroke with a time of onset unavailable due to aphasia, impaired consciousness, or cognitive impairment (non-wake-up unknown onset stroke, non-WUS). We aimed to assess the differences in efficacy and safety of intravenous thrombolysis (IVT) for these subgroups. Methods: Patients with an unknown onset stroke from the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing IVT with placebo/standard treatment. A favorable outcome was defined as a modified Rankin Scale score 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22-36 hours and 90-day mortality. The effect of IVT was compared between the treatment groups in the WUS and non-WUS with mixed-effect logistic-regression analysis. Results: A total of 634 patients (233 women [36.8%], median age 70 years [IQR 61-76]) were analyzed. In patients with non-WUS (n=92 [14%]), advanced age, atrial fibrillation, vessel occlusion on MRA and high NIHSS score were more prevalent (P&lt;0.01 for each) than those with WUS (n=542 [86%]). Overall, no significant interaction was noted between the mode of onset and treatment effect (Pinteraction=0.782). In patients with WUS, a favorable outcome was more common in the IVT group than the control (149 [54.8%] vs. 117 [45.5%], adjusted OR: 1.45, 95% CI 1.01-2.11), death occurred in 11 [4.0%] and 5 [1.9%] (p=0.099), and sICH occurred in 5 [1.8%] and 1 [0.3%] (p=0.142). In patients with non-WUS, no significant difference was observed for a favorable outcome (16 [37.2%] vs. 14 [29.2%], aOR 1.73 [0.60-4.98]). One death and one sICH were reported in the IVT group, but none in the controls. Conclusions: The benefit of IVT was significant in patients with WUS. Excellent outcome was also numerically more prevalent in non-WUS but this did not reach significance, probably due to the lack of statistical power.

Efficacy and safety of intravenous thrombolysis in mild ischemic stroke

Background: Intravenous thrombolysis is the preferred clinical treatment for ultra-early (&lt;4.5 h) ischemic stroke. However, whether intravenous thrombolysis should be used in patients with mild stroke remains controversial. This study reports a systematic review and meta-analysis of the efficacy and safety of intravenous thrombolysis in acute mild stroke. Methods: The PubMed, Cochrane Library, MEDLINE, Embase and CBM disc databases were searched for studies on intravenous thrombolysis versus nonthrombolysis in acute mild stroke. All studies published in English prior to March 2022 were retrieved. The studies were screened and selected based on the inclusion and exclusion criteria. Then, the data were extracted and recorded by trained researchers. RevMan 5.4 statistical software was used to analyze the data on the efficacy (mRS score, stroke recurrence rate and mortality at 90 days) and safety (intracranial hemorrhage, symptomatic intracranial hemorrhage) of the patients with acute mild stroke in the intravenous thrombolysis and nonthrombolysis groups. Results: A total of 14 high-quality studies containing 86,063 patients with acute mild stroke (8,824 in the intravenous thrombolysis group; 77,239 in the nonthrombolysis group) were included in this meta-analysis. The meta-analysis results were as follows: (1) Efficacy: There were significant differences in mRS scores of 0~1 and 0~2 between the intravenous thrombolysis and nonthrombolysis groups (mRS 0-1, OR= 1.53, 95% CI: 1.31~1.79, Z=5.40, P &lt;0.00001; mRS 0-2, OR= 1.33, 95% CI: 1.07~1.65, Z=2.59, P =0.01). (2) Safety: There was no significant difference in the recurrence rate of stroke or mortality between the two groups ( recurrence rate, OR= 0.62, 95% CI: 0.35~1.08, Z=1.68, P =0.09; mortality, OR=0.89, 95% CI: 0.45~1.77, Z=0.33, P =0.74). There were more patients with intracranial hemorrhage in intravenous thrombolysis group than in nonthrombolysis group (asymptomatic intracranial hemorrhage, OR= 2.39, 95% CI:1.19~4.80, Z=2.45, P =0.01; symptomatic intracranial hemorrhage, OR= 7.65, 95% CI:3.07~19.05, Z=4.37, P &lt;0.0001). Conclusion: Intravenous thrombolysis significantly improved the functional outcomes but did not reduce mortality at 90 days in patients with acute mild stroke and had a higher risk of intracranial hemorrhage.

Thrombolysis in central retinal artery occlusion: a retrospective observational study

BackgroundThere is no evidence-based therapy for non-arteritic central retinal artery occlusion (NA-CRAO). Intravenous thrombolysis (IVT) with alteplase in a time window < 4.5 h may lead to a favorable outcome. Purpose of this study was to investigate the feasibility, efficacy and safety of IVT in patients classified as functionally blind.MethodsWe conducted a retrospective observational study of NA-CRAO-patients. All patients underwent an ophthalmological and neurological examination including cerebral magnetic resonance imaging (MRI) for assessment of additional stroke lesions. Patients were treated either conservatively or with IVT within 4.5 h. Visual acuity (VA) was evaluated in logMAR and a categorical analysis was performed.ResultsThirty-seven patients were included in the study, 21 patients in the conservative treatment group (CTG) and 16 patients in the IVT group. The median logMAR visual acuity at admission and discharge was similar in both groups. The medium symptom to treatment time in the IVT group was 158.0 min. 3 patients (19%) of the IVT group showed a favorable outcome, all CTG patients remained at the level of functional blindness. No serious adverse events were observed after IVT. MRI showed additional acute stroke in over one-third of the patients (n = 14).ConclusionsEarly intravenous thrombolysis therapy according to the current stroke protocol n a time window up to 4.5 h after the onset of symptoms was feasible and might be a potential treatment option for NA-CRAO. Patients with NA-CRAO are at very high risk of ischemic stroke and MRI should be done in all patients for optimized treatment and secondary stroke prevention. A prospective randomized study is required.

A meta-analysis of intravenous thrombolysis versus bridging therapy for ischemic stroke.

Background:The purpose of this study was to perform a pooled analysis of randomized controlled trials (RCT) of intravenous thrombolysis (IVT) versus bridging therapy of intravenous thrombolysis and mechanical thrombectomy (IVMT), comparing the efficacy and safety of the two in patients with acute ischemic stroke (AIS).Methods:All eligible RCT articles from database establishment to December 8, 2021 were searched in databases such as PubMed, Ovid, Embase, Web of science, Cochrane Library, etc. Efficacy outcomes were assessed by modified RANKIN scal (mRS) score, complete recanalization or reperfusion (TICI), National Institute of Health Stroke Scal (NIHSS) score, 90-day mortality, 24 to 36 h incidence of symptomatic intracranial hemorrhage (sICH).Results:Our study included 6 RCT involving 1717 patients. The proportion of the primary efficacy outcome (mRS score 0‐2 at 90 days) was significantly different between IVT and IVMT (OR 0.51; 95% CI 0.35‐0.76). For the secondary efficacy outcome, the study found a significant difference in the proportion of TICI (pooled OR was 0.055, 95% CI 0.07‐0.33). There was a significant difference in the 24 h NIHSS score between the IVT group and the IVMT group (pooled MD was 3.25, 95% CI 0.80‐5.70). There were no significant differences in the NIHSS score at 90 days, the death rate at 90 days, and the sICH at 24 to 36 hours between the two groups.Conclusions:This study confirms that IVMT is more effective and safe than IVT alone in patients with AIS. However, more and higher-quality randomized clinical trials comparing IVMT to IV alone are warranted for validation.

Intravenous Thrombolysis Improves the Prognosis of Patients with Acute Ischemic Stroke and Chronic Kidney Disease

BackgroundChronic kidney disease (CKD) is associated with a higher mortality rate and a poor prognosis among patients with acute ischemic stroke (AIS) who receive intravenous thrombolysis (IVT); however, it is still unclear whether IVT improves the prognosis of patients with AIS and CKD. ObjectiveWe conducted this study to evaluate the impact of IVT in patients with AIS and CKD. MethodsWe analyzed patients with AIS and CKD in 3 stroke centers who met the indications for IVT between January 2015 and January 2020. The patients were grouped into an IVT group and a non-IVT group according to whether patients received IVT. After propensity score matching at a 1:1 ratio, symptomatic intracranial hemorrhage (sICH) and the modified Rankin Scale (mRS) score at 3 months were compared to assess the safety and efficacy of IVT in patients with AIS with CKD. ResultsA total of 888 patients were enrolled: 763 in the IVT group and 125 in the non-IVT group. After matching, 250 patients were analyzed, and no significant differences were found in sICH between the 2 groups. However, the IVT group had a better 90-day mRS (0–2) score (70.4% vs. 57.6; p = 0.048) than the non-IVT group. ConclusionsIVT improved the 3-month prognosis and did not increase the occurrence of sICH among patients with AIS with CKD.

Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability: A Meta-Analysis.

Randomized controlled trials for the use of alteplase in acute ischemic stroke have excluded or had little representation of patients with prestroke disability, and the benefit of alteplase in this population remains uncertain. We performed a systematic review and meta-analysis to examine the outcomes of thrombolysis in patients with premorbid disability. We performed a systematic review in accordance with the Meta-Analysis of Observational Studies in Epidemiology guidelines and retrieved studies reporting intravenous thrombolysis (IVT) in patients with prestroke disability (modified Rankin Scale score, 3-5) with acute ischemic stroke, either compared with untreated patients or treated patients without premorbid disability. The primary outcome was the return to premorbid disability at 90 days. Secondary outcomes included rate and odds ratio of favorable functional outcome at 90 days (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. Eight articles were included involving 103 988 patients. Patients with disability treated with IVT had better odds of returning to baseline function compared with those who did not receive IVT (odds ratio, 7.26 [95% CI, 2.51-21.02]). Mortality and rates of sICH were not significantly different between patients with disability treated with IVT and those not treated, although there were numerically more sICHs in the IVT group. Return to baseline function was not significantly different between patients with and without prestroke disability (odds ratio, 1.46 [95% CI, 0.75-2.83]). The rates of sICH were not significantly different in patients with and without premorbid disability. However, mortality was 3× higher in patients with premorbid disability than in those without premorbid disability (38.2% versus 12.6%). The use of IVT in patients with disability was associated with better outcomes compared with patients who did not receive IVT without statistically significant added risks of sICH or mortality. When compared with those without disability, there was no significant difference in the return to baseline function or sICH. High-quality data comparing treated versus untreated patients with premorbid disability are needed to clarify this issue. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.