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

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 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.

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 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).

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 ◽  
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.

scholarly journals Low-Dose Versus Standard-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke in Asian Populations

Medicine ◽  
2015 ◽  
Vol 94 (52) ◽  
pp. e2412 ◽  
Author(s):  
Meng-Dong Liu ◽  
Wei-Dong Ning ◽  
Ren-Cong Wang ◽  
Wei Chen ◽  
Yang Yang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Low Dose ◽  
Standard Dose ◽  
Asian Populations ◽  
Tissue Plasminogen
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