scholarly journals Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke

Neurology ◽  
2021 ◽  
Vol 96 (11) ◽  
pp. e1512-e1526
Author(s):  
Zien Zhou ◽  
Candice Delcourt ◽  
Chao Xia ◽  
Sohei Yoshimura ◽  
Cheryl Carcel ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Treatment Effects ◽  
Low Dose ◽  
Standard Dose ◽  
Clinical Trial Registration ◽  
Logistic Regression Models ◽  
Stroke Study ◽  
Post Hoc ◽  
Different Levels

ObjectiveTo determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.MethodsIn a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified 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 or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.ResultsOf 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2–6, adjusted odds ratio [95% confidence interval] 0.60 [0.47–0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2–6, 1.04 [0.87–1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all pinteraction ≥0.07).ConclusionsWe found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.Classification of EvidenceThis study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.Clinical Trial RegistrationClinicaltrials.gov identifier NCT01422616.

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.

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 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).

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

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.

scholarly journals Lipid-Lowering Pretreatment and Outcome Following Intravenous Thrombolysis for Acute Ischaemic Stroke: A Post Hoc Analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study Trial

2018 ◽  
Vol 45 (5-6) ◽  
pp. 213-220 ◽  
Author(s):  
Jatinder S. Minhas ◽  
Xia Wang ◽  
Hisatomi Arima ◽  
Philip M. Bath ◽  
Laurent Billot ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Low Dose ◽  
Standard Dose ◽  
Intravenous Thrombolysis ◽  
Lipid Lowering ◽  
Stroke Study ◽  
Number Of Patients ◽  
Intravenous Alteplase ◽  
Post Hoc

Background: Debate exists as to whether statin pretreatment confers an increased risk of 90-day mortality and symptomatic intracranial haemorrhage (sICH) in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis. We assessed the effects of undifferentiated lipid-lowering pretreatment on outcomes and interaction with low-dose versus standard-dose alteplase in a post hoc subgroup ­analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study. Methods: In all, 3,284 thrombolysis-eligible AIS patients (mean age 66.6 years; 38% women), with information on lipid-lowering pretreatment, were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 h of symptom onset. Of the total number of patients, 615 (19%) received statin or other lipid-lowering pretreatment. The primary clinical outcome was combined endpoint of death or disability (modified Rankin Scale scores 2–6) at 90 days. Results: Compared with patients with no lipid-lowering pretreatment, those with lipid-lowering pretreatment were significantly older, more likely to be non-Asian and more likely to have a medical history including vascular co-morbidity. After propensity analysis assessment and adjustment for important baseline variables at the time of randomisation, as well as imbalances in management during the first 7 days of hospital admission, there were no significant differences in mortality (OR 0.85; 95% CI 0.58–1.25, p = 0.42), or in overall ­90-day death and disability (OR 0.85, 95% CI 0.67–1.09, p = 0.19), despite a significant decrease in sICH among those with ­lipid-lowering pretreatment according to the European Co-operative Acute Stroke Study 2 definition (OR 0.49, 95% CI 0.28–0.83, p = 0.009). No differences in key efficacy or safety outcomes were seen in patients with and without lipid-lowering pretreatment between low- and standard-dose alteplase arms. Conclusions: Lipid-lowering pretreatment is not associated with adverse outcome in AIS patients treated with intravenous alteplase, whether assessed by 90-day death and disability or death alone.

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 Thrombolysis with Low-Dose Versus Standard-Dose Alteplase in 4.5 Hours After Acute Ischemic Stroke; A Four-Months Prospective Study.

2020 ◽  
pp. 1-13
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Ischemic Stroke ◽  
Systolic Blood Pressure ◽  
Cerebral Hemorrhage ◽  
Low Dose ◽  
Standard Dose ◽  
Favorable Outcome ◽  
Safety And Efficacy ◽  
To Receive

Abstract Background: In Japan, Pakistan and Vietnam, 0.6 mg of Alteplase per kilogram body weight within 3 hours was approved for standard guideline, although the safety and efficacy in acute ischemic stroke within 4.5 hours has not been established. We conducted four-month prospective study to compare the safety and efficacy of 0.6 mg, 0.75 mg and 0.9 mg of Alteplase per kilogram body weight. Methods: In cohort A, the patients were randomly assigned to receive intravenous 0.6 mg or 0.75 mg or 0.9 mg of Alteplase per kilogram body weight in a 1:1:1. Interim analysis was performed after complete cohort A. In cohort B, patients were assigned to receive 0.9 mg of Alteplase per kilogram body weight (standard-dose). The primary end points were death, favorable outcome at discharge and 90-day and intra-cerebral hemorrhage. The secondary end points were good outcomes, Improved mRS at discharged and 90-day, number of patients with length of hospital stay <7 days and overall complications. Results: In Cohort A, 78 were randomly assigned to receive 0.6 mg or 0.75 mg (low-dose) or 0.9 mg of intravenous Alteplase per kilogram body weight. Less patients had favorable outcomes in 0.6 mg and 7.5 mg than 0.9 mg of Alteplase per kilogram body weight at discharge (P=0.0004) and at 90-day (P=0.05). In Cohort B, 330 were assigned to receive standard-dose Alteplase. Finally, 408 patients were enrolled with median time of Alteplase administration by 2 hours 49 min. There was no different onset to needle and death between low-dose and standard-dose Alteplase (P=0.82 and P=0.85). Less patients had favorable outcome and intra-cerebral hemorrhage with low-dose than standard-dose Alteplase (favorable outcomes: Relative risk (RR), 1.18; 95% confidence interval (CI), 1.09 to 1.27; P <0.001 at discharge and RR, 1.25; 95%CI, 1.07 to 1.46; P=0.003 at 90 day, intra-cerebral hemorrhage: RR, 0.05; 95%CI, 0.00 to 0.95; P=0.04. Less patients had improved modified Rankin Scale [mRS] at 90-day with low-dose than standard-dose Alteplase (RR, 1.66; 95%CI, 1.22 to 2.25; P=0.001; especially in the patients with initial systolic blood pressure <180 mmHg ; RR, 1.86; 95%CI, 1.35 to 2.56; P=0.0001). In patients with initial systolic blood pressure >180 mmHg, low-dose Alteplase group had more patients with mRS of 0-3 at 90-day and less patients with of mRS 4-6 at 90-day than standard-dose Alteplase (P=0.002). There was no significant different in length of stay and overall complications with low-dose than standard-dose Alteplase (P=0.15). Conclusion: As compared with standard-dose, intravenous low-dose Alteplase administered within 4.5 hours after the onset of stroke significant less favorable outcome, intra-cerebral hemorrhage, but not different in death, especially in the patients with initial systolic blood pressure <180 mmHg. However, patients with initial systolic blood pressure >180 mmHg, intravenous low-dose Alteplase had less patients with disability and death and more patient’s recovery with mRS of 0-3 at 90-day. (ClinicalTrial.gov Number, NCT03847883).

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