Low-Dose Intra-Arterial Urokinase and Aggressive Mechanical Clot Disruption for Acute Ischemic Stroke after Failure of Intravenous Thrombolysis

Objective: Although intravenous thrombolysis (IVT) using alteplase for octogenarians with acute ischemic stroke becomes relatively familiar, it is unclear whether IVT for nonagenarians is a futile intervention. The purpose of this study is to clarify the efficacy and safety of IVT using low-dose alteplase (0.6 mg/kg) for nonagenarians compared with octogenarians. Methods: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA registry retrospectively collected 600 consecutive acute stroke patients receiving IVT from 10 Japanese stroke centers between October 2005 and July 2008. We extracted all octogenarians (O group) and nonagenarians (N group) from the registry. We compared baseline characteristics, symptomatic intracranial hemorrhage (SICH), and 3-month outcomes between the groups. 3-month outcomes include; functional independence (FI) defined as a mRS score 0-2, good outcome (GO) as a mRS score 0-2 or same as the premorbid mRS, poor outcome (PO) defined as a mRS score 5-6, and death. Results: Twenty-five nonagenarians (mean age, 93 years) and 124 octogenarians (mean age, 84 years) were included. N group was more female-predominant (76% versus 56%, p=0.06) and premorbidly dependent (44% versus 14%, p<0.001) than O group. There were no significant differences of median baseline NIHSS score (16 versus 14, p=0.95) and Alberta Stroke Program Early CT Score (9 versus 9, p=0.36) between the groups. The rate of FI tended to be lower in N group than O group (16% versus 36%, p=0.06), otherwise, the differences of the rates of GO (28% versus 37%, p=0.39), PO (40% versus 36%, p=0.73), death (20% versus 11%, p=0.23) and SICH (0% versus 2.4%, p=1.00) were not significant between the groups. In comparison with O group, N group was not associated with 3-month clinical outcomes (FI; OR 0.61; 95% CI, 0.15-2.42, GO; 0.98; 0.31-3.07, PO; 0.63; 0.15-2.70, death; 3.18; 0.62-16.3) and SICH (0.68; 0.17-2.69) after multivariate adjustment. Conclusions: IVT using low-dose alteplase for N group resulted in less frequent achievement of FI mainly because of more premorbid dependency than O group, however, showed at least a similar safety and a potential efficacy.

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Abstract TMP25: Effects of Age and Ethnicity on the Benefits and Risks of Low- versus Standard-dose Alteplase in Acute Ischemic Stroke Patients: The Enchanted Trial

Stroke ◽

10.1161/str.48.suppl_1.tmp25 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Xia Wang ◽

Thompson Robinson ◽

Hisatomi. Arima ◽

Joseph Broderick ◽

Andrew Demchuk ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Treatment Effects ◽

Low Dose ◽

Standard Dose ◽

Intravenous Thrombolysis ◽

Open Label ◽

Poor Outcome ◽

Symptomatic Intracerebral Hemorrhage ◽

Stroke Study

Background and Purpose: As lower doses of alteplase reduce the risk of symptomatic intracerebral hemorrhage (sICH), older and Asian people may benefit more from low-dose alteplase than other patients with acute ischemic stroke (AIS). Methods: Data from the ENhanced Control of Hypertension ANd Thrombolysis strokE study (ENCHANTED), an international, multi-center, prospective, randomized, open-label, blinded-endpoint trial, were analyzed to assess effects of low- (0.6mg/kg body weight) vs. standard-dose (0.9mg/kg) alteplase in AIS patients, by age and ethnicity (Asian vs. non-Asian), pre-specified subgroup analyses, on key efficacy and safety outcomes. Results: 3297 patients (1248 female), mean age 67 years were included. After adjusting for baseline characteristics and management variables over the first seven days, increasing age was associated with poor outcome, defined by ordinal analysis of the modified Rankin score (mRS) (shift to a less favorable outcome, P trend <0.0001). In the comparison between low- and standard-dose alteplase, no significant differences were observed for 90-day poor outcome by age deciles and ethnicity. Less sICH was observed with low-dose alteplase, and this was consistent for age and ethnicity. There was no ethnic difference in the treatment effects by age, severity, and time to treatment. Conclusions: Increasing age predicts poor outcome in thrombolysis-treated AIS patients. There was no heterogeneity in the treatment effects of low- vs. standard-dose alteplase. Decisions about intravenous thrombolysis should be based on variables other than age and ethnicity.

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Intravenous Thrombolysis With Low-Dose Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.109.573113 ◽

2010 ◽

Vol 41 (3) ◽

Cited By ~ 1

Author(s):

Pei Kee Loh ◽

Vijay K. Sharma

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Low Dose ◽

Intravenous Thrombolysis ◽

Recombinant Tissue Plasminogen Activator ◽

Tissue Plasminogen

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Low-dose versus standard-dose alteplase for intravenous thrombolysis in patients with acute ischemic stroke in Iran: Results from the safe implementation of treatments in stroke registry

Current Journal of Neurology ◽

10.18502/cjn.v20i4.8346 ◽

2022 ◽

Author(s):

Elyar Sadeghi-Hokmabadi ◽

Abdoreza Ghoreishi ◽

Reza Rikhtegar ◽

Payam Sariaslani ◽

Shahram Rafie ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Odds Ratio ◽

Dose Group ◽

Low Dose ◽

Standard Dose ◽

Intravenous Thrombolysis ◽

Standard Group ◽

Eastern Region ◽

Significant Difference

Background: Rates of intracranial hemorrhage (ICH) after intravenous thrombolysis (IVT) differ depending regard are scarce in the Middle Eastern region. Methods: The present retrospective study was performed on data extracted from the Safe Implementation of Treatments in Stroke (SITS) registry. Computed tomography (CT) image analysis was based on the SITS-Monitoring Study (SITS-MOST) definition for symptomatic ICH (SICH). Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Multivariate logistic regression including adjusted analysis was used for comparison between groups. Results: Of 6615 patients, 1055 were enrolled. A total of 86% (n = 906) received a standard dose and 14% (n = 149) received a low dose of alteplase. Favorable 3-month outcome was achieved in 481 (53%) patients in the standard group and 71 (48%) patients in the low-dose group [adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI): 0.87-1.75, P = 0.218]. SICH occurred in 14 (1.5%) patients in the standard group and 3 (2%) patients in the low-dose group [odds ratio (OR) = 2.77, 95% CI: 0.36-21.04, P = 0.120]. At 3 months, mortality occurred in 145 (16.0%) patients in the standard group and 29 (19.4%) patients in the low-dose group (OR = 1.22, 95% CI: 0.78-1.91, P = 0.346). Conclusion: Low-dose compared to standard-dose alteplase for patients with acute ischemic stroke (AIS) was not associated with fewer hemorrhagic events and there was no significant difference in the favorable 3-month outcome (mRS: 0-2) or mortality rate.

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Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry

Frontiers in Neurology ◽

10.3389/fneur.2021.666919 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gaoting Ma ◽

Shuo Li ◽

Baixue Jia ◽

Dapeng Mo ◽

Ning Ma ◽

...

Keyword(s):

Ischemic Stroke ◽

Propensity Score ◽

Acute Ischemic Stroke ◽

Propensity Score Matching ◽

Clinical Improvement ◽

Low Dose ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Stroke Patients

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p > 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy.

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Outcomes and Treatment Complications of Intravenous Urokinase Thrombolysis in Acute Ischemic Stroke in China

Frontiers in Neurology ◽

10.3389/fneur.2021.685454 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rongrong Zhang ◽

Hui Wei ◽

Yu Ren ◽

Yanping Wu ◽

Yetao Luo ◽

...

Keyword(s):

Multivariate Analysis ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Low Dose ◽

Multivariate Analyses ◽

Univariate Analysis ◽

Intravenous Thrombolysis ◽

High Dose ◽

Stroke Patients ◽

Treatment Complications

Background: Intravenous thrombolysis with alteplase benefits eligible patients with acute ischemic stroke. However, in some countries such as China, alteplase may be too expensive for low-income patients, and also for regions with low economic development. Urokinase is much less expensive than alteplase. This study aimed to assess the outcomes and treatment complications of urokinase in acute ischemic stroke patients, which are poorly understood.Methods: This multicenter retrospective study included acute ischemic stroke patients who received intravenous urokinase or alteplase from January 2014 to January 2018 at 21 centers in China. Outcomes and treatment complications were analyzed by univariate and multivariate analyses.Results: Among the 618 patients included in this study, 489 were treated with urokinase and 129 were treated with alteplase. Functional independence, no/minimal disability, mortality, intracranial hemorrhage (ICH), and symptomatic ICH did not significantly differ between the urokinase and alteplase groups in the univariate and multivariate analyses. However, the patients who received alteplase had a lower odds ratio (OR) of extracranial bleeding in the univariate analysis and a lower adjusted OR (aOR) in the multivariate analysis than the patients who received urokinase (OR = 0.410 [95% CI, 0.172–0.977], p = 0.038; aOR = 0.350 [95% CI, 0.144–0.854], p = 0.021). Furthermore, in patients treated with urokinase, the patients who received high-dose urokinase had a higher OR of extracranial bleeding in the univariate analysis and a higher aOR of extracranial bleeding in the multivariate analysis than patients who received low-dose urokinase (OR = 3.046 [95% CI, 1.696–5.470], p < 0.001; aOR = 3.074 [95% CI, 1.627–5.807], p = 0.001). Moreover, patients who received low-dose urokinase had similar outcomes and complications compared to patients treated with alteplase.Conclusions: Patients treated with urokinase had similar outcomes but a higher risk of extracranial bleeding compared to patients treated with alteplase. The risk of extracranial bleeding was higher in the patients treated with high-dose urokinase than in the patients treated with low-dose urokinase. Patients who received low-dose urokinase had similar outcomes and complications compared to patients treated with alteplase. In countries such as China where some acute ischemic stroke patients cannot afford alteplase, urokinase may be a good alternative to alteplase for intravenous thrombolysis.

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Low-Dose Versus Standard-Dose Tissue Plasminogen Activator for Intravenous Thrombolysis in Asian Acute Ischemic Stroke Patients

Stroke ◽

10.1161/strokeaha.110.582403 ◽

2010 ◽

Vol 41 (8) ◽

Cited By ~ 2

Author(s):

Kay W.P. Ng ◽

Vijay K. Sharma

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Low Dose ◽

Standard Dose ◽

Intravenous Thrombolysis ◽

Stroke Patients ◽

Tissue Plasminogen

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Pre-treatment of Single and Double Antiplatelet and Anticoagulant With Intravenous Thrombolysis for Older Adults With Acute Ischemic Stroke: The TTT-AIS Experience

Frontiers in Neurology ◽

10.3389/fneur.2021.628077 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sheng-Feng Lin ◽

Han-Hwa Hu ◽

Bo-Lin Ho ◽

Chih-Hung Chen ◽

Lung Chan ◽

...

Keyword(s):

Older Adults ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Low Dose ◽

Standard Dose ◽

Intravenous Thrombolysis ◽

Safety And Efficacy ◽

Logistic Regression Models ◽

Symptomatic Intracranial Hemorrhage ◽

Pre Treatment

Background: This study aimed to investigate the safety and efficacy of single antiplatelet, anticoagulant and Dual Antiplatelet pre-treatment (DAPP) in older, moderate to high severity acute ischemic stroke patients treated with intravenous thrombolysis (IVT).Methods: A prospective cohort study was conducted to monitor the development of symptomatic intracranial hemorrhage (SICH) and functional outcomes at 90 days. Two different dosages of alteplase were used for IVT. Logistic regression models were used for analysis of the safety and efficacy outcomes.Results: A total of 1,156 patients were enrolled and categorized into six groups based on their pre-treatment medications: (1) aspirin (n = 213), (2) clopidogrel (n = 37), (3) DAPP of aspirin + clopidogrel (n= 27), (4) warfarin (n = 44), (5) any of the above pre-medications (n = 331), and (6) none of these medications as controls (n = 825). The DAPP group showed significantly increased SICH by the NINDS (adjusted OR: 4.90, 95% CI 1.28–18.69) and the ECASS II (adjusted OR: 5.09, 95% CI: 1.01–25.68) standards. The aspirin group was found to significantly improve the favorable functional outcome of the modified Rankin Scale (mRS) of 0–1 (adjusted OR: 1.91, 95% CI, 1.31.2.78), but no significance for mRS of 0–2 (adjusted OR: 1.39, 95% CI, 0.97–1.99). The DAPP group also significantly increased mortality (adjusted OR: 4.75, 95% CI: 1.77–12.72). A significant interaction between different dosages for IVT and the functional status was noted. Compared to standard dose, the DAPP group showed higher proportions of disability and mortality with low dose of IVT.Conclusion: For older adults with higher baseline severity of acute ischemic stroke, DAPP may increase the risk of SICH and mortality post IVT. However, DAPP is still not an indication to withdraw IVT and to prescribe low-dose IVT for older adults.

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