Comparative Analysis on Low- and Standard-Dose Regimes of Alteplase Thrombolytic Therapy for Acute Ischemic Stroke: Efficacy and Safety

2017 ◽  
Vol 79 (1-2) ◽  
pp. 68-73 ◽  
Author(s):  
Guangjian Zhao ◽  
Tingfen Huang ◽  
Mei Zheng ◽  
Yansen Cui ◽  
Yunyong Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Dose Group ◽  
Low Dose ◽  
Standard Dose ◽  
Efficacy And Safety ◽  
Significant Difference ◽  
Symptomatic Intracranial Hemorrhage ◽  
Intravenous Alteplase

Objective: This study analyzed the efficacy and safety of low-dose and standard-dose alteplase intravenous thrombolytic therapy for acute ischemic stroke (AIS). Methods: Patients with AIS who underwent intravenous alteplase thrombolysis from July 2012 to December 2016 were retrospectively analyzed and correspondingly divided into low-dose (0.6–0.89 mg/kg) group and standard-dose group (0.9 mg/kg) according to alteplase dosage. The clinical outcome was evaluated by modified Rankin Scale (mRS) at 90 days after onset. The safety index was the mortality at 90 days after onset and the incidence of symptomatic intracranial hemorrhage (SICH) within 7 days. Results: A total of 1,486 patients were included (1,115 cases in low-dose group and 371 cases in standard-dose group). There were no significant differences in baseline data between the 2 groups. As mRS, good outcome rate as well as mortality rate in both groups had no significant difference (36.1 vs. 37.6%; χ2 = 10.882, p = 0.890; 5.5 vs. 7.3%; χ2 = 2.163, p = 0.076), but the incidence of SICH in low-dose group was significantly lower than that of the standard-dose group (2.2 vs. 5.9%; χ2 = 3.157, p = 0.001). Conclusion: The efficacy of low-dose alteplase intravenous thrombolytic therapy for AIS was equivalent to the standard-dose regimen but with higher safety.

scholarly journals 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

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.

Abstract T P48: Intravenous Thrombolysis Using Low-Dose Alteplase for Nonagenarians with Acute Ischemic Stroke: The SAMURAI rtPA Registry

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mikito Hayakawa ◽  
Masatoshi Koga ◽  
Shoichiro Sato ◽  
Shoji Arihiro ◽  
Yoshiaki Shiokawa ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Dose ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
Efficacy And Safety ◽  
Multivariate Adjustment ◽  
Potential Efficacy ◽  
Symptomatic Intracranial Hemorrhage ◽  
Baseline Characteristics

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.

scholarly journals Low-dose versus standard-dose alteplase in acute ischemic stroke in Asian stroke registries: an individual patient data pooling study

2019 ◽  
Vol 14 (7) ◽  
pp. 670-677
Author(s):  
Xia Wang ◽  
Jingwei Li ◽  
Tom J Moullaali ◽  
Keon-Joo Lee ◽  
Beom Joon Kim ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Real World ◽  
Low Dose ◽  
Standard Dose ◽  
Stroke Registry ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Intravenous Alteplase

Objective To investigate the comparative efficacy and safety of the low-dose versus standard-dose alteplase using real-world acute stroke registry data from Asian countries. Methods Individual participant data were obtained from nine acute stroke registries from China, Japan, Philippines, Singapore, South Korea, and Taiwan between 2005 and 2018. Inverse probability of treatment weight was used to remove baseline imbalances between those receiving low-dose versus standard-dose alteplase. The primary outcome was death or disability defined by modified Rankin Scale scores of 2 to 6 at 90 days. Secondary outcomes were symptomatic intracerebral hemorrhage and death. Generalized linear mixed models with the individual registry as a random intercept were performed to determine associations of treatment with low-dose alteplase and outcomes. Results Of the 6250 patients (mean age 66 years, 36% women) included in these analyses, 1610 (24%) were treated with low-dose intravenous alteplase. Clinical outcomes for low-dose alteplase were not significantly different to those for standard-dose alteplase, adjusted odds ratios for death or disability: 1.00 (0.85–1.19) and symptomatic intracerebral hemorrhage 0.87 (0.63–1.19), except for lower death with borderline significance, 0.77 (0.59–1.01). Conclusions The present analyses of real-world Asian acute stroke registry data suggest that low-dose intravenous alteplase has overall comparable efficacy for functional recovery and greater potential safety in terms of reduced mortality, to standard-dose alteplase for the treatment of acute ischemic stroke.

More on Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

2018 ◽  
Vol 378 (15) ◽  
pp. 1465-1466 ◽  
Author(s):  
Craig S. Anderson ◽  
Mark Woodward ◽  
John Chalmers
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Dose ◽  
Standard Dose ◽  
Intravenous Alteplase

scholarly journals Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

2016 ◽  
Vol 374 (24) ◽  
pp. 2313-2323 ◽  
Author(s):  
Craig S. Anderson ◽  
Thompson Robinson ◽  
Richard I. Lindley ◽  
Hisatomi Arima ◽  
Pablo M. Lavados ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Dose ◽  
Standard Dose ◽  
Intravenous Alteplase

scholarly journals WSO EXPRESS: Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target

2021 ◽  
pp. 174749302110254
Author(s):  
Zien Zhou ◽  
Chao Xia ◽  
Grant Mair ◽  
Candice Delcourt ◽  
Sohei Yoshimura ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Statistical Power ◽  
Standard Dose ◽  
Blood Pressure Target ◽  
Significant Difference ◽  
Intravenous Alteplase ◽  
Vascular Obstruction

Background: We explored the influence of low-dose intravenous alteplase and intensive blood pressure (BP) lowering on outcomes of acute ischemic stroke (AIS) according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended BP lowering in AIS patients. In those who had baseline CT or MRI angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration [END], and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models. Results: There were 940 participants: 607 in alteplase arm only, 243 in BP arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56-2.90] but comparable in MVO (1.34 [0.96-1.88]) groups. There were no differences in associations of alteplase dose or BP lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54-1.30]/0.48 [0.25-0.91]/0.99 [0.75-2.09], Pinteraction=0.28; intensive versus standard BP lowering 1.32 [0.74-2.38]/0.78 [0.31-1.94]/1.24 [0.64-2.41], Pinteraction=0.41), except for a borderline significant difference for intensive BP lowering and increased END (0.63 [0.14-2.72]/0.17 [0.02-1.47]/2.69 [0.90-8.04], Pinteraction=0.05). Conclusions: Functional outcome by dose of alteplase or intensity of BP lowering is not modified by vascular obstruction status/site according to analyzes from ENCHANTED, although these results are compromised by low statistical power.

scholarly journals Abstract MP3: Low Dose versus Standard Dose Alteplase in Acute Lacunar Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Zien Zhou ◽  
Candice Delcourt ◽  
Chao Xia ◽  
Sohei Yoshimura ◽  
Cheryl Carcel ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Regression Models ◽  
Treatment Effects ◽  
Low Dose ◽  
Standard Dose ◽  
Efficacy And Safety ◽  
Logistic Regression Models ◽  
Stroke Study ◽  
Intravenous Alteplase ◽  
Different Levels

Objective: To identify any differential efficacy and safety of low- versus standard-dose intravenous alteplase for lacunar versus non-lacunar acute ischemic stroke (AIS) in the alteplase dose-arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: In a cohort of 3297 ENCHANTED participants, we identified those with lacunar or non-lacunar AIS with different levels of confidence (definite/probable/possible) according to pre-specified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration [END] or death) and treatment effects of low- versus standard-dose alteplase across lacunar and non-lacunar AIS with adjustment for baseline covariables. Results: Of 2588 participants with available imaging and clinical data, we classified cases as definite or probable lacunar (n=490) or non-lacunar AIS (n=2098) for primary analyses. Regardless of the alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% CI] 0.60 [0.47-0.77]) and other clinical or safety outcomes, compared to participants with non-lacunar AIS. Overall, low-dose alteplase (compared to standard) had no differential effect on the functional outcome (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of ICH. There were no differential treatment effects of low- versus standard-dose alteplase on all outcomes across lacunar and non-lacunar AIS (all P interaction ≥0.07). Conclusions: We found no clear evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard-dose for definite/probable lacunar AIS.

scholarly journals Who will benefit more from low-dose alteplase in acute ischemic stroke?

2019 ◽  
Vol 15 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Xia Wang ◽  
Keon-Joo Lee ◽  
Tom J Moullaali ◽  
Beom Joon Kim ◽  
Qiang Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Dose ◽  
Standard Dose ◽  
Modified Rankin Scale ◽  
Stroke Patients ◽  
Lower Systolic Blood Pressure ◽  
Intravenous Alteplase

Objectives Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk–benefit balance of low-dose alteplase treatment. Methods Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. Results Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). Conclusion Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.

scholarly journals Interaction of Blood Pressure Lowering and Alteplase Dose in Acute Ischemic Stroke: Results of the Enhanced Control of Hypertension and Thrombolysis Stroke Study

2019 ◽  
Vol 48 (3-6) ◽  
pp. 207-216
Author(s):  
Xia Wang ◽  
Lili Song ◽  
Jie Yang ◽  
Lingli Sun ◽  
Tom J. Moullaali ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Recovery ◽  
Low Dose ◽  
Standard Dose ◽  
Safety Outcome ◽  
Stroke Study ◽  
Pressure Lowering ◽  
Intravenous Alteplase

Objective: To determine the extent to which the effects of intensive blood pressure (BP) lowering are modified by doses of alteplase in thrombolysis-eligible acute ischemic stroke (AIS) patients. Methods: Prespecified analyses of the Enhanced Control of Hypertension and Thrombolysis Stroke Study for patients enrolled in both arms: (i) low-dose (0.6 mg/kg body weight) or standard-dose (0.9 mg/kg) alteplase and (ii) intensive (target systolic BP [SBP] 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP management. The primary outcome was functional recovery, measured by a shift in scores on modified Rankin scale at 90 days. The safety outcome was any intracranial hemorrhage (ICH). Results: There were 925 participants (mean age 67 years, 39% female, 77% Asian) randomized to both arms: 242 randomly assigned to guideline/standard-dose (GS); 234 to guideline/low-dose (GL); 227 to intensive/standard-dose (IS); and 222 to intensive/low-dose (IL). Overall, average SBP levels within 24 h were lower in the low-dose compared to standard-dose alteplase group (146 and 144 vs. 151 and 150 mm Hg, for GS and GL vs. IS and IL, respectively, p < 0.0001). There was no heterogeneity of the effects of BP lowering (intensive vs. guideline) on functional recovery between standard-dose (OR 0.81, 95% CI 0.59–1.12) and low-dose alteplase (1.06, 0.77–1.47; p = 0.25 for interaction). Similar results were observed for ICH (p = 0.50 for interaction). Conclusions: In thrombolysis-treated patients with predominantly mild-to-moderate severity AIS, intensive BP lowering neither improve functional recovery, either with low- or standard-dose intravenous alteplase, nor beneficially interact with low-dose alteplase in reducing ICH. Trial Registration: The trial is registered with ClinicalTrials.gov (NCT01422616).

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