Intra-arterial Reteplase and Intravenous Abciximab in Patients with Acute Ischemic Stroke: An Open-label, Dose-ranging, Phase I Study

Neurosurgery ◽  
2006 ◽  
Vol 59 (4) ◽  
pp. 789-797 ◽  
Author(s):  
Adnan I. Qureshi ◽  
Pansy Harris-Lane ◽  
Jawad F. Kirmani ◽  
Nazli Janjua ◽  
Afshin A. Divani ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Favorable Outcome ◽  
Platelet Glycoprotein ◽  
Open Label ◽  
Neurological Improvement ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Label Dose

Abstract OBJECTIVE: New approaches are focusing on using a combination of medication that lyse fibrin and prevent aggregation of platelets to achieve higher rates of recanalization and improved clinical outcomes. METHODS: A prospective, nonrandomized, open-label trial evaluated the safety of an escalating dose of reteplase in conjunction with intravenous abciximab (platelet glycoprotein IIb/IIIa inhibitor) in patients with acute ischemic stroke (3–6 h after symptom onset). The primary endpoint was symptomatic intracerebral hemorrhage at 24 to 72 hours, and secondary endpoints were partial or complete recanalization (≥ one grade improvement), early neurological improvement (decrease in National Institutes of Health Stroke Scale ≥ 4 at 24 h), and favorable outcome at 1 month (defined by modified Rankin scale ≤ 2). RESULTS: A total of 20 patients (mean age, 65 yr; 13 men) were recruited. Five patients were recruited in each of the escalating tiers of intra-arterial reteplase (0.5, 1, 1.5, and 2 units). Intravenous abciximab (0.25 mg/kg bolus followed by 0.125 μg/kg/min) was successfully administered in 18 out of 20 patients. The safety stopping rule was not activated in any of the tiers. One symptomatic intracerebral hemorrhage was observed in one of the 20 patients (in the 1-unit tier). Partial or complete recanalization was observed in 13 of the 20 patients. Thirteen patients demonstrated early neurological improvement, and favorable outcome at 1 month was observed in six patients. CONCLUSION: In this study, a combination of intra-arterial reteplase and intravenous abciximab was safely administered to patients with ischemic stroke presenting between 3 and 6 hours after symptom onset.

Abstract 3275: Early Neurological Improvement After Intravenous Thrombolysis in Acute Stroke Predicts Long-Term Functional Outcome

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Leonard L Yeo ◽  
Liang Shen ◽  
Ben Wakerley ◽  
Aftab Ahmad ◽  
Kay W Ng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Symptom Onset ◽  
Functional Outcomes ◽  
Treatment Time ◽  
Favorable Outcome ◽  
Stroke Patients ◽  
Neurological Improvement ◽  
Iv Tpa

Background: Intravenously administered tissue plasminogen activator (IV-TPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Wide variations in the rates and timing of neurological recovery are observed in thrombolyzed patients. While all IV-TPA treated patients are routinely evaluated for neurological recovery at 24-hours, considerable improvement occurs in some cases within 2-hours of treatment initiation. We evaluated whether early neurological improvement at 2-hours after IV-TPA bolus (ENI-2) can predict functional outcomes in thrombolyzed AIS patients at 3-months. Methods: Data for consecutive stroke patients treated with IV-TPA within 4.5 hours of symptom-onset during 2007-2010 were prospectively entered in the thrombolyzed registry maintained at our tertiary care center. Data were collected for demographic characteristics, vascular risk factors, stroke subtypes and blood pressure levels before IV-TPA bolus. National Institute of Health Stroke Scale (NIHSS) scores were obtained before IV-TPA bolus and at 2-hours. ENI-2 was defined as a reduction in NIHSS score by more than 10-points from baseline score or an absolute score of 4-points or less at 2-hours after IV-TPA bolus. Functional outcomes at 3-months were determined by modified Rankin scale (mRS). Data were analyzed by SPSS 19.0. Results: Of the 2238 AIS patients admitted during the study period, 240 (11%) received IV-TPA within 4.5-hours of symptom-onset. Median age was 65yrs (range 19-92), 63% males, median NIHSS 17points (range 3-35) and median onset-to-treatment time 149 minutes. Overall, 122 (50.8%) patients achieved favorable functional outcome (mRS 0-1) at 3-months. Factors associated with favorable outcome at 3-months on univariable analysis were younger age, female gender, presence of atrial fibrillation, baseline NIHSS, onset-to-treatment time (OTT) and ENI-2. However, multivariable analysis demonstrated NIHSS at onset (OR per 1-point increase 0.907, 95%CI 0.848-0.969) and ENI-2 (OR 4.926 95%CI 1.66-15.15) as independent predictors of favorable outcome at 3-months. Conclusion: Early Neurological improvement at 2-hours after IV-TPA bolus is a strong predictor of the functional outcome at 3-months in acute ischemic stroke patients.

Abstract T P66: Safety and Effectiveness of Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients on Aspirin and Clopidogrel

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Mushtaq H Qureshi ◽  
Shayaan M Khan ◽  
Nauman Jahangir ◽  
Ahmed A Malik ◽  
Melissa Freese ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Combination Therapy ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Recombinant Tissue Plasminogen Activator ◽  
Favorable Outcome ◽  
Stroke Patients ◽  
Neurological Improvement ◽  
Tissue Plasminogen

Background: The number of acute ischemic stroke patients who are on both aspirin and clopidogrel treatment at time of acute ischemic event is increasing. There is limited data regarding the safety and efficacy of intravenous recombinant tissue plasminogen activator (rt-PA) treatment in such patients. Methods: We reviewed the medical records and imaging data of consecutive patients with acute ischemic stroke who received IV rt-PA within 4.5 hours of symptom onset. We stratified the patients based on active regular use of antiplatelet medications: monotherapy (aspirin or clopidogrel), combination therapy (aspirin and clopidogrel), and no therapy and compared the rates of symptomatic intracerebral hemorrhage (ICH), neurological improvement (≥4 points in National Institutes of Health Stroke Scale [NIHSS], and favorable outcome (modified Rankin scale [mRS] 0-1) at discharge between the three groups. Results: A total of 88 acute ischemic stroke patients (mean age±SD; 69.88 ±15) were treated with IV rt-PA within the study duration. Of the 88 patients 45 (50.6%), 37 (41.6%), and 52 (58.4) were on monotherapy, combination therapy, or no therapy at time of presentation. The proportion of patients who developed symptomatic ICHs were similar (p=0.8) in monotherapy, combination therapy, and no therapy groups (3.3%, 0.0%, and 4.1%, respectively). The rates of neurological improvement were greater in patients on monotherapy (20%) (p=0.03) followed by combination therapy (11.1%), and no therapy groups (2.0%). There was no significant reduction in the rate of favorable outcome at discharge among patients on combination treatment compared with no treatment (odds ratio 0.8 , 95% confidence interval 0.4-1.8 ) after adjusting for age and initial NIHSS score strata (<10, 10-19, and ≥20). Conclusions: Compared with patients on no antiplatelet treatment, acute ischemic stroke patients who are actively using aspirin and clopidogrel appear to have similar risks and benefits with IV rt-PA treatment.

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 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 Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0–5

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 880-888 ◽  
Author(s):  
Johannes Kaesmacher ◽  
Panagiotis Chaloulos-Iakovidis ◽  
Leonidas Panos ◽  
Pasquale Mordasini ◽  
Patrik Michel ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Mechanical Thrombectomy ◽  
Functional Independence ◽  
Favorable Outcome ◽  
Large Vessel Occlusion ◽  
Stroke Patients ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Symptomatic Intracerebral Hemorrhage

Background and Purpose— If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0–5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0–5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods— Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration—URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0–3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0–2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results— Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0–5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363–12.961), functional independence (aOR, 5.583; 95% CI, 1.964–15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083–0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062–0.887). The mortality-reducing effect remained in patients with ASPECTS 0–4 (aOR, 0.167; 95% CI, 0.056–0.499). Sensitivity analyses did not change the primary results. Conclusions— In patients presenting with ASPECTS 0–5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.

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