Thrombolysis For Acute Ischemic Stroke Research Articles

Direct mechanical thrombectomy with or without thrombolysis for acute ischemic stroke

Direct mechanical thrombectomy with or without thrombolysis for acute ischemic stroke

Intravenous tenecteplase for acute ischemic stroke between 4.5 and 6 h of onset (EXIT-BT2): Rationale and Design

Rationale: To date, the benefit of intravenous thrombolysis for acute ischemic stroke (AIS) patients without advanced neuroimaging selection is confined to within 4.5 h of onset. Our phase II EXIT-BT (Extending the tIme window of Thrombolysis by ButylphThalide up to 6 h after onset) trial suggested the safety, feasibility, and potential benefit of intravenous tenecteplase (TNK) in AIS between 4.5 and 6 h of onset. The EXIT-BT2 trial is a pivotal study undertaken to confirm or refute this signal. Aim: To investigate the efficacy and safety of TNK for AIS between 4.5 and 6 h of onset with or without endovascular treatment. Sample size estimates: A maximum of 1440 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance, stratified by age, sex, history of diabetes, location of vessel occlusion, baseline National Institute of Health stroke scale score, stroke etiology, and plan for endovascular treatment. Design: EXIT-BT2 is a prospective, randomized, open-label, blinded assessment of endpoint (PROBE), and multi-center study. Eligible AIS patients between 4.5 and 6 h of onset are randomly assigned 1:1 into a TNK group or control group. The TNK group will receive TNK (0.25 mg/kg, a single bolus over 5–10 s, maximum 25 mg). The control group will receive standard medical care in compliance with national guidelines for acute ischemic stroke. Both groups will receive standard stroke care from randomization to 90 days after stroke onset according to national guidelines. Outcome: The primary efficacy endpoint is excellent functional outcome, defined as a modified Rankin Scale score 0–1 at 90 days after randomization, while the primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 24 (−6/+12) h after randomization. Conclusions: The results of EXIT-BT2 may determine whether intravenous TNK has a favorable risk/benefit profile in AIS between 4.5 and 6 h of onset.

The use of Panax notoginseng saponins injections after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis.

As a bioactive metabolite preparation widely used in acute ischemic stroke (AIS), the efficacy and safety of Panax notoginseng saponins injections (PNSI) in patients with AIS after intravenous thrombolysis remain to be evaluated. This study included randomized controlled trials published before 26 April 2024 in 8 databases. AIS patients who received intravenous thrombolysis were included. The control group receiving conventional treatment and the treatment group receiving additional PNSI. Primary outcomes were selected as mortality, disability, and adverse events. Secondary outcomes were selected as all-cause mortality, improvement of neurological deficit, quality of life, and cerebral injury indicators. The revised Cochrane Risk of Bias tool was used to assess risk of bias. Risk ratio (RR) and mean differences (MD) were calculated for binary variables and continuous variables, respectively, based on a 95% confidence interval (CI). A total of 20 trials involving 1,856 participants were included. None of them reported mortality or disability. There was no significant difference in the adverse events [RR: 1.04; 95% CI: 0.60 to 1.81] and hemorrhagic transformation [RR: 0.99; 95% CI: 0.36 to 2.70] between the two groups. Compared to the control group, the treatment group had a better effect in neurological improvement assessed by National Institutes of Health Stroke Scale [MD: -2.91; 95% CI: -4.76 to -1.06], a better effect in activities of daily living changes in Barthel Index [MD: 9.37; 95% CI: 1.86 to 16.88], and a lower serum neuron-specific enolase level [MD: -2.08; 95% CI: -2.67 to -1.49]. For AIS patients undergoing intravenous thrombolysis, the use of PNSI improved neurological deficits and enhanced activity of daily living in the short term without increasing the occurrence rate of adverse events. However, due to the moderate to very low certainty of evidence, it is advisable to conduct high-quality clinical trials to validate the findings of this study. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=466851, Identifier CRD42023466851.

Predictors of Early versus Delayed Neurological Deterioration after Thrombolysis for Ischemic Stroke

Introduction: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24–72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2–6 vs. 0–1 and 3–6 vs. 0–2 and death). Results: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02–1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04–1.09), patients from Asia (OR 1.25, 95% CI 1.03–1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47–0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p < 0.001). Conclusion: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days.

Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample.

Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

Analysis of Safety and Efficacy of the Early Initiation of Antithrombotic Secondary Prevention in Patients Treated with Intravenous Thrombolysis for Acute Ischemic Stroke.

Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological deterioration, which we could prevent with the early administration of antithrombotic therapy. We do not know the effect of early antithrombotic therapy after intravenous thrombolysis with rt-PA in acute stroke on the outcome in patients after 90 days either. Design: Prospective monocentric observational cohort study. Methods: Data were collected from consecutive patients treated with alteplase for acute ischemic stroke between January 2015 and January 2023. We examined functional outcome at 90 days, including the risk of symptomatic intracranial hemorrhage and mortality rate as safety indicators and stroke recurrence events in both early and standard antithrombotic therapy at 24 h after intravenous thrombolysis. Results: A total of 489 patients were included, of which 278 (56.9%) were men. Of these, 407 (83.2%) patients received early antithrombotic therapy. No symptomatic intracranial hemorrhage occurred in any participants. There was a significantly higher number of patients with an excellent outcome (mRS 0-1) in early antithrombotic treatment (211 (53.1%) versus 28 (34.6%) in standard antithrombotic treatment (p = 0.002, OR 0.47, 95% CI: 0.28-0.76). Conclusions: Early antithrombotic treatment after intravenous therapy in patients with acute ischemic stroke revealed no safety concerns compared with standard antithrombotic therapy and resulted in a significantly higher proportion of patients with an excellent functional outcome.

Challenging the management of blood pressure before intravenous thrombolysis in acute ischaemic stroke

Challenging the management of blood pressure before intravenous thrombolysis in acute ischaemic stroke

Comparative Analysis of Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Multicentric Observational Study from Eastern India.

Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke. To compare the effectiveness and adverse effects of tenecteplase and alteplase in the real-world management of acute ischemic stroke. In this retrospective observational study, we collected data from acute ischemic stroke patients admitted in six hospitals in West Bengal, India, and were thrombolysed with tenecteplase or alteplase between July 2021 and June 2022. Demographic data, baseline parameters, hospital course, and 3-month follow-up data were collected. The percentage of patients achieving a score of 0-2 in the modified Ranking scale at 3 months, rate of symptomatic intracranial hemorrhage, and all-cause mortality within 3 months were the main parameters of comparison between the two thrombolytic agents. A total of 162 patients were initially included in this study. Eight patients were excluded due to unavailability of follow-up data. Among the remaining patients, 71 patients received tenecteplase and 83 patients received alteplase. There was no statistically significant difference between tenecteplase and alteplase with respect to the percentage of patients achieving functional independence (modified Rankin scale score 0-2) at 3 months (53.5% vs. 60.2%, P = 0.706), rate of symptomatic intracranial hemorrhage (5.6% vs. 10.8%, P = 0.246), and all-cause mortality at 3 months (11.3% vs. 15.7%, P = 0.628). The effectiveness of tenecteplase is comparable to alteplase in the real-world management of acute ischemic stroke. Symptomatic intracranial hemorrhage and all-cause mortality rates are also similar in real-world practice.

Comprehensive Review of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase. Animal studies have demonstrated the favorable pharmacokinetics and pharmacodynamics of tenecteplase. Moreover, it is easier to administer. Clinical trials have demonstrated that tenecteplase is not inferior to alteplase and may even be superior in cases of acute ischemic stroke with large vessel occlusion. Current evidence supports the time and cost benefits of tenecteplase, suggesting that it could potentially replace alteplase as the main option for thrombolytic therapy, especially in patients with large vessel occlusion.

Case report: Tenecteplase for acute ischemic stroke after heparin reversal

Intravenous thrombolysis can be administered to appropriate patients with suspected acute ischemic strokes who are on intravenous heparin infusions after its rapid reversal with protamine sulfate. Several case reports suggest the safety of tissue-type plasminogen activator, or alteplase, in these scenarios. Noting the increasing preferential use of tenecteplase over alteplase for intravenous thrombolysis of acute ischemic stroke, the safe and efficacious use of tenecteplase following heparin reversal has not been demonstrated in the literature. Our case demonstrates successful use of intravenous tenecteplase in a patient who was anticoagulated with therapeutic heparin. The patient had no hemorrhagic complications and had an excellent neurological outcome.

Urban-rural inequalities in IV thrombolysis for acute ischemic stroke: A nationwide study.

Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units. In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights. Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%-18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5-17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7-19.4). While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies.

Safety and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with History of Intracranial Hemorrhage within the Florida Stroke Registry (S10.001)

Safety and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with History of Intracranial Hemorrhage within the Florida Stroke Registry (S10.001)

Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19min and 137min, respectively. Hemorrhagic expansion (N=8, 66.67%) and inhospital mortality (N=7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.

312 Mechanical Thrombectomy With or Without Intravenous Thrombolysis for Acute Ischemic Stroke Due to Distal and Medium Vessel Occlusions: A Propensity Score Matching of Patients From 41 Academic Centers

INTRODUCTION: To date, studies evaluating mechanical thrombectomy (MT) in distal and medium vessel occlusions (DMVOs) have failed to establish conclusive, high-quality evidence for its clinical benefit. METHODS: Between January 2017 and January 2022, characteristics and outcomes of patients with DMVOs treated with MT or MT + IVtPA were collected at 41 academic centers in North America, Asia, and Europe. Using R software version 4.2.3, propensity score matching using the nearest neighbor matching by controlling for all relevant variables, followed by appropriate descriptive statistics and multivariate logistic regression. RESULTS: After propensity score matching, all differences between groups were resolved, and there was a total of 577 patients included (315 MT alone and 262 MT +IVT). Patients treated with MT + IVT achieved greater rates of TICI 2b-3 (OR = 1.79, 95% CI = 1.02-3.15; P-value= 0.043) than those treated with MT alone, and the rate of modified Rankin score (mRS) 0-2 was greater in the MT + IVT group (n = 171, 65.3%) compared to the MT alone (n = 181, 57.5%) group (OR = 1.52, 95% CI= 1.03-2.24; p-value = 0.034). Sixty-nine patients experienced 90-day mortality, and the rate was comparable between the MT + IVtPA group (n = 30, 11.5%) and the MT alone (n = 39, 12.4%) group (OR = 0.9, 95% CI = 0.53-1.54; p-value = 0.71). Of note, the rate of intracranial hemorrhage (all types) was similar between the MT + IVtPA and MT alone group (OR = 0.85, 95% CI = 0.58-1.26; p-value = 0.43). CONCLUSIONS: MT + IVT showed higher efficacy than MT alone in patients with DMVOs, without higher risks.

Hemorrhagic transformation after acute ischemic stroke thrombolysis treatment: navigating the landscape of hemostasis genetic risk factors

Hemorrhagic transformation after acute ischemic stroke thrombolysis treatment: navigating the landscape of hemostasis genetic risk factors

Correlation of Peripheral Blood Inflammatory Indicators to Prognosis After Intravenous Thrombolysis in Acute Ischemic Stroke: A Retrospective Study.

According to many previous studies, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and hypersensitive C-reactive protein (CRP) are commonly used as important indicators to assess the prognosis of intravenous thrombolysis in AIS patients. Based on this, we used two novel biomarkers C-NLR (CRP/neutrophil-to-lymphocyte ratio) and C-LMR (CRP×lymphocyte-to-monocyte ratio) to investigate their correlation with 90-day outcomes in AIS patients after intravenous thrombolysis. A total of 204 AIS patients who received intravenous thrombolysis at the Stroke Center of Jiangsu Province Hospital of Chinese Medicine from January 2021 to December 2022 were retrospectively included. All patients were followed up 90 days after thrombolysis to assess their prognosis. Patients with a modified Rankin scale score (mRS) of 3-6 were included in the unfavorable outcome group, and those with a score of 0-2 were included in the favorable outcome group. Logistic regression analysis, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival curve were used to investigate the association between C-NLR, C-LMR, and 90-day prognosis in AIS patients treated with early intravenous thrombolysis. C-NLR (OR=1.586, 95% CI=1.098~2.291, P=0.014) and C-LMR (OR=1.099, 95% CI=1.025~1.179, P=0.008) were independent risk factors for 90-day prognosis of AIS patients treated with early intravenous thrombolysis. The higher C-NLR and C-LMR were associated with unfavorable prognosis. C-NLR and C-LMR can be used as biomarkers to predict prognosis of AIS patients treated with early intravenous thrombolysis.

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.

Endovascular thrombectomy with versus without intravascular thrombolysis for acute ischaemic stroke

Endovascular thrombectomy with versus without intravascular thrombolysis for acute ischaemic stroke

Abstract WMP8: Tenecteplase vs Alteplase: is Pro-Inflammatory and Procoagulant Response Any Different in Acute Ischemic Stroke?

Introduction: Thrombolysis in acute ischemic stroke (AIS) using Tenecteplase (TNK) is gaining popularity compared to Alteplase (ALT) for its practical advantages. At our center, we observed an improvement in clinical outcome in TNK treated patients compared to ALT. Hence, we aimed to study the pro-inflammatory and procoagulant responses post-thrombolysis and their contributory role in clinical outcome. Methods: This is a single-center retrospective study of ALT or TNK treated AIS patients admitted to a comprehensive stroke center over a 3-year period. Non-parametric tests were used to compare differences between the ALT and TNK cohorts. Peripheral blood indices, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), and mean platelet volume to platelet count ratio (MPV:PLT), were calculated. Their rise from pre-thrombolysis baseline during the first 48 hours was used to define a systemic inflammatory and procoagulant response. A p-value of &lt;0.05 was considered statistically significant. Results: During the study period, 165 and 64 patients were treated with ALT and TNK respectively. The baseline demographics, vascular risk factors, and admission stroke severity were similar. Admission NLR, PLR, MLR, and MPV:PLT were not statistically different. Clinical outcome at 3 months assessed using median modified Rankin Scale (mRS) was better with TNK (2.0 [IQR, 1.0, 4.0] vs 3.0 [IQR, 2.0, 5.0]; p = 0.0007). Rise in NLR was significantly higher in the ALT cohort compared to TNK on day 1 (2.25 [IQR, 0.0, 5.77] vs. 0.49 [IQR, -0.48, 3.91], p = 0.01) and day 2 (1.58 [IQR, -0.09, 5.68] vs. 0.39 [IQR, -0.96, 2.91], p = 0.045). Similarly, MLR on day 2 in the ALT cohort (0.16 [IQR, 0.05, 0.49] vs. 0.12 [IQR, -0.05, 0.22], p = 0.038) and MPV:PLT on day 1 (0.61 [IQR, 0.16, 1.35] vs. 0.32 [IQR, 0.003, 0.68], p = 0.002) and day 2 (0.83 [IQR, -0.35, 1.90] vs. 0.36 [IQR, -0.12, 1.21], p = 0.004) were higher. Conclusions: Patients treated with TNK had better mRS scores compared to ALT in our study. This was associated with significantly less inflammatory and procoagulant response during the first 48 hours of AIS in the TNK group. The etiology for such an association is speculative and needs confirmation using more specific biomarkers.

Abstract WP21: Intravenous Alteplase for Unknown Onset Stroke on Prior Antiplatelet Therapy: EOS Individual Participant Data

Introduction: Although prior antiplatelet therapy (APT) could potentially contribute to bleeding risk, the influence of prior APT on intravenous thrombolysis outcomes remains controversial. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke in patients receiving prior APT Methods: Patients with an acute stroke of unknown onset were evaluated using an individual patient-level database of randomized controlled trials comparing t-PA with placebo or standard care from the Evaluation of Unknown Onset Stroke Thrombolysis (EOS) trials. A favorable outcome was defined as a modified Rankin Scale of 0 to 1 at 90-days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22 to 36 hours and 90-day mortality. Results: Baseline data on prior APT were available for 780 of 843 patients. Of these, 257 (32.9%) patients were receiving prior APT. Patients with prior APT were older (72 vs. 66 years), and had a higher prevalence of vascular risk factors than those without APT. Overall, there was no interaction between prior APT and treatment effects of alteplase (p interaction=0.23). A favorable outcome was observed in 55 of 125 (45%) patients with prior APT in the alteplase group and in 39 of 132 (30%) patients with prior APT in the control group (adjusted odds ratio [aOR], 2.41 [95% CI, 1.14-5.13]). sICH occurred in 7 patients (5.6%) in the alteplase group but in 1 patient (0.8%) of the controls (aOR, 10.82 [0.63-185.3]). 90-day mortality was observed in 6 patients (6.5%) in the alteplase group compared with 6 patients (6.1%) in the controls (aOR, 1.47 [0.25-8.78]). In patients without prior APT (n=523), favorable outcome was observed in 136 patients (51.3%) in the alteplase group and in 112 patients (45.3%) in the control group (aOR, 1.38 [0.90-2.11]). Additionally, no significant differences were found in terms of safety outcomes between the two groups (sICH: 3 [1.2%] vs. 1 [0.4%]; mortality: 13 [4.9%] vs. 3 [1.1%]). Conclusion: Intravenous alteplase exhibited efficacy for acute stroke without increasing the risks of symptomatic intracranial hemorrhage or mortality in patients with prior antiplatelet therapy.