Abstract 2281: Full Dose IV-tPA Followed By IA Therapy For Acute Ischemic Stroke Does Not Increase Morbidity Or Mortality

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Jeffrey M Katz ◽  
Calvin Natanzon ◽  
Avi Setton ◽  
Richard Libman

Background and Purpose: “Bridging Therapy” is well described in the literature. However the dose of bridging tissue plasminogen activator (tPA) is a matter of debate given the well-established guideline of 0.9 mg/kg as the standard intravenous dose. Previous and ongoing bridging trials use lower doses of IV-tPA (0.6 mg/kg) with a goal of maximizing safety. Our aim was to explore whether full bridging dose IV-tPA at 0.9 mg/kg can be given safely in combination with intra-arterial (IA)-tPA. Methods: Data were collected prospectively on 47 consecutive patients with acute ischemic stroke who were treated with endovascular stroke therapy (EST, that is IA-tPA +/- mechanical embolectomy (ME)). Patients who were candidates for IV-tPA, who did not clinically improve after receiving full dose IV-tPA (0.9mg/Kg), underwent EST (bridging group, n=23, 15/23 IA-tPA + ME). These patients were compared to patients treated with EST alone because they were not candidates for IV-tPA (control group, n=24, 14/24 IA-tPA + ME). Symptomatic intracranial hemorrhage (ICH) rates were recorded, as defined in the NINDS IV-tPA trial. Death rates were recorded at one month and modified Rankin score was used to measure functional outcome (6 month mean follow-up). Results: Mean age was 62 years in the bridging group and 63 years in the control group. Baseline mean National Institute of Health Stroke Scale was 20 in the bridging group and 21 in the control group (p = 0.188). The mean IA-tPA dose was 14.4 mg in the bridging group and 18.3 mg in the control group (p = 0.371). There was an 8% risk of symptomatic ICH in the control group and no symptomatic ICH in the bridging group (p = 0.155). At 30 days, mortality was 17% in the bridging group and 29% in the control group (p = 0.313). The mean follow-up modified Rankin score was 3 in the bridging group and 4 in the control group (p = 0.20). Conclusion: This non-randomized retrospective cohort study suggests that full dose IV-tPA combined with IA-tPA administered during EST is safe in patients with acute ischemic stroke. Given the possibility that full bridging dose tPA may be more effective than lower dose IV-tPA, a prospective, randomized bridging trial using full dose IV-tPA may be warranted.

Author(s):  
Elisabeth B Marsh ◽  
Erin Lawrence ◽  
Rafael H Llinas

Background and Objective: The National Institute of Health Stroke Scale (NIHSS) is the most commonly used metric to evaluate stroke severity and improvement following intervention. Despite its advantages as a rapid, reproducible screening tool, it may be too insensitive to adequately capture functional improvement following treatment. We evaluated the difference in rate of improvement by previously accepted criteria (change of ≥4 NIHSS points) versus physician documentation in patients receiving IV tissue plasminogen activator (tPA) for acute ischemic stroke. Methods: Prospectively collected data on all patients receiving IV tPA over a 15 month period were retrospectively reviewed. NIHSS 24 hours post-treatment and on discharge were extrapolated based on examination and compared to NIHSS on presentation. NIHSS scores at post-discharge follow-up were also recorded. Two reviewers evaluated the medical record and determined improvement based on physician documentation. Using tests of proportion, ‘significant improvement’ by NIHSS was compared to physician documentation at each time point. Results: Forty-one patients were treated with IV tPA. The mean admission NIHSS was 8.6 and improved to 6.4 24 hours post-tPA. Twenty-nine of 41 patients (79%) were “better” by documentation; however only 11/41 (27%) met NIHSS criteria for improvement (p compared to documentation <0.001). On discharge, 20/41 patients (49%) met NIHSS criteria for improvement; however a significant difference between physician documentation remained (p=0.04). The mean post-discharge follow-up NIHSS score was 2.0. 20/21 patients (95%) were “better” compared to 16/21 (76%) meeting NIHSS criteria (p=0.08). Conclusion: The NIHSS may inadequately capture functional improvement post-treatment, especially in the days immediately following intervention.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Tapan Abrol ◽  
Zeeshan Hussain ◽  
Varun Chaubal ◽  
Gaurav Dighe ◽  
Muhammad F Bilal ◽  
...  

Introduction: People aged 90 years or older are the fastest growing group in North America. This group was excluded from traditional clinical trials of intravenous tissue plasminogen activator (iv tPA) thrombolysis. IV tPA is the most beneficial emergent therapy in acute ischemic stroke (AIS). We have compassionately treated AIS patients in this age group with iv tPA in recent years. Hypothesis: Our aim is to evaluate the safety and outcome of iv tPA use in nonagenarian patients with AIS Methods: Consecutively iv tPA-treated AIS patients who were older than 90 years and were admitted at our institution from January 2004-June 2015 were included. The administration of iv tPA was within 3 hours after the stroke onset. We reviewed the clinical features of the patients at presentation, complications, and outcomes. Outcome measures at discharge included improvement of NIHSS, mRS, symptomatic intracranial hemorrhage (sICH), and discharge disposition. We also assessed the rate of complications of iv tPA. Multiple logistic regression analysis was used to evaluate association between the outcome versus the severity of stroke, or versus pre-stroke dependence. Results: A total of 35 AIS patients who were 90 years or older (female 80%; and median age 93 years old) were treated with iv tPA. At baseline twenty-two patients (62.9%) had a history of atrial fibrillation without anticoagulation, and more than half (20/35) patients needed assistance for gait instability, but they were otherwise functional. Median NIHSS on admission was 16 (IQR 9-22). Two patients (5.7%) had symptomatic intracerebral hemorrhage. At discharge the median NIHSS was 10 (IQR 1-19). Ten patients (28.6%) had favorable outcome (mRS ≤ 2) while sixteen patients (45.7%) had good outcome (mRS ≤ 3). Four patients were discharged home and 16 patients went to rehabilitation facility. Fifteen patients (42.9%) succumbed to cardio-pulmonary failure or were discharged to hospice. Mild AIS patients (NIHSS <7) had better outcomes (p < 0.05). The pre-existing dependence (mRS ≥3) did not predict poor outcome. Conclusion: It is safe to administer iv tPA to AIS patients who are 90 years or older although the benefits are less robust compared to younger patients. Patients with milder deficits had more favorable outcomes.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Javaad Ahmad ◽  
Mohammed Hussain ◽  
Siddhart Mehta ◽  
Jaskiran Brar ◽  
Harina Chahal ◽  
...  

Background and Objective: It is considered unconventional to initiate antiplatelet regimen within 24 hours of IV tPa administration in acute ischemic strokes. There has been an increasing amount of literature assessing combination therapy of IV r- tPA and IV Eptifibatide in acute ischemic stroke. Our objectives were to evaluate the safety (hemorrhagic complications) and efficacy (discharge mRS) of administering IV Eptifibatide within the first 24 hours of receiving full dose IV r-tPA respectively. Materials and Methods: All patients that presented to our university affiliated stroke center from 2010-13 with an acute ischemic stroke were included and retrospectively classified into two groups. Group A underwent full dose IV r- tPa (.9 mg/kg) (+/- Endovascular intervention). Group B underwent full dose IV r-tPa (.9mg/kg) and IV Eptifibatide (+/- Endovascular intervention). Epitafibide was administered as a bolus of 135 mcg/kg IV followed by .5 mcg/kg/min for 20 hours. The primary endpoint of bleeding is classified as major (symptomatic intracranial hemorrhage or hemoglobin decrease by >5 mg/dl), minor (asymptomatic intracranial hemorrhage or hemoglobin decrease by 3-5 mg/dl) and insignificant as proposed by TIMI score. The efficacy endpoint was discharge mRS of 0-1 as favorable, with 2 and above being unfavorable. Results: We reviewed 2,016 patients with ischemic stroke, of which 170 received IV tPA. Among the group, 118 received IV r-tPa alone and 52 received combined modalities of IV r-tPa and IV Eptifibatide. In group A, there were 7 patients who had a major complication of symptomatic intracranial hemorrhage, while 1 patient had a minor complication of asymptomatic intracranial hemorrhage. In group B, there were 3 patients who had major complication of symptomatic intracranial hemorrhage and 5 with minor complications of asymptomatic intracranial hemorrhage. In group A , 9% (n=4) had a favorable outcome (OR=2.389, 95% CI 0.6645 to 8.589, p= 0.2217). Of the 52 patients in group B, 18% (n=8) had a favorable outcome. Conclusion: IV Eptifibatide, within the first 24 hours of ischemic stroke in combination with full dose IV r-tPA was found to be safe and efficacious. Further, larger prospective trials are needed to corroborate our findings.


2018 ◽  
Vol 5 (9) ◽  
pp. 2697-2702
Author(s):  
Mojtaba Khazaei ◽  
Zaher Khazaei ◽  
Elham Goodarzi ◽  
Ali Ghadimi

Background: Acute ischemic stroke is caused by blockage of a cerebral artery and is also known as cerebrovascular accident (CVA). Recombinant tissue plasminogen activator (rt-PA) therapy is effective in reducing early and long-term neurologic disabilities if it is started quickly. Therefore, the aim of this study was to determine the efficacy of treatment with recombinant tissue plasminogen activators in improving the clinical status of acute ischemic stroke. Methods: The current study was performed as a clinical trial of two groups- treatment and control (n=20 per group). The treatment group consisted of patients who received rt-PA, while the control group consisted of patients who did not receive rt-PA. For each group, evaluation of neurological disabilities following ischemic stroke was based off the National Institutes of Health Stroke Scale (NIHSS), for early assessment of disability on the third day of treatment), and off the modified Rankin Scale (MRS) at 90 days after stroke. The drug effect criterion was used to reduce the neurological disability or the difference in NIHSS on day 3 after treatment. Also, the duration of onset of symptoms until the arrival of the patients to the emergency room (ER), as well as the risk factors, complications and number of deaths in both groups, were recorded. Data obtained were analyzed by SPSS software. Results: The results of the study showed that the mean of ER arrival time, NIHSS before treatment, and NIHSS on day 3 of treatment in the control group was higher than that of the treatment group; the difference was statistically significant (P<0.05). The results also indicated that the probability of improvement of neurological disabilities in the experimental group was greater than that of the control group (relative risk (RR) =1.25). Additionally, the odds ratio (OR) for receiving rt-PA in the NIHSS positive treatment group compared to the control group was equal to 1/5 (OR=1.5). The results showed that 30% of the patients in the treatment group were treated with a complication. The mean of MRS was higher in the control group at 90 days after the stroke, compared with the treatment group. Conclusion: Treatment with rt-PA reduces the neurological disability in patients with ischemic stroke, since the mean of MRS is lower in the treatment group, compared with the control group, after 90 days of treatment.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jeffrey Leya ◽  
Elisabeth Donahey ◽  
Megan Rech

Introduction: Early treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset is associated with neurologic improvement. A risk of rtPA is hemorrhagic conversion, which has a higher incidence in patients with elevated blood pressure at presentation. Current literature supports the use of blood pressure goals (<185/110 mm Hg) in patients qualifying for rtPA, but the effects of anti-hypertensive (anti-HTN) medications within the first 24 hours of AIS on outcomes has not been evaluated. Hypothesis: AIS patients requiring anti-HTN medications (anti-HTN group) before rtPA have a poorer outcome at 90 days compared to those that do not need anti-HTN medications (control group). Methods: This was a retrospective cohort study of patients >18 years diagnosed with AIS from January 2011 through December 2015 who received one or multiple anti-HTN medication(s) prior to rtPA administration, compared to control patients who did not. Primary endpoint was poor outcome at 90 days, defined as a modified Rankin Scale (mRS) of ≥3. Univariate analysis with Chi-square, Fisher’s exact test or t-test was performed. Multivariate analysis was conducted. Results: Of 235 patients evaluated for AIS, 145 (61.7%) were included. Baseline demographics were well matched, though more patients in the anti-HTN group had a history of HTN (86.7% vs. 62.5%, p<0.01), diabetes (33.3% vs. 17.5%, p=0.04) and chronic kidney disease (20% vs. 7.5%, p=0.04). There was no difference in the primary endpoint of poor outcome (mRS ≥3) between groups who received blood pressure medication versus those who did not (37% anti-HTN group vs. 30% control, p=.374). There was no difference in hemorrhagic conversion (13.3% anti-HTN group vs. 6.3% control, p=.187). Mortality at 90 days did not differ between groups (11% who received anti-HTN vs. 7.5%, p=.508). Conclusion: No difference was observed in poor outcomes, hemorrhagic conversion, or 90-day mortality in patients receiving anti-HTN medications prior to rtPA compared to those that did not. These results suggest that aggressive blood pressure management should be used to control hypertension in AIS who may qualify for rtPA, though larger, randomized trials are needed to confirm this finding.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jiang He ◽  
Yonghong Zhang ◽  
Tan Xu ◽  
Dali Wang ◽  
Chung-Shiuan Chen ◽  
...  

Although elevated blood pressure (BP) is very common in patients with acute ischemic stroke, the management of hypertension among them remains controversial. We tested the effect of immediate BP reduction on two-year mortality and major disability in acute ischemic stroke patients. The China Antihypertensive Trial in Acute Ischemic Stroke, a randomized, single-blind, blinded end-points trial, was conducted in 4,071 patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment (n=2,038) or to discontinue all antihypertensive medications (n=2,033) during hospitalization. Post-treatment follow-ups were conducted at 3, 12, and 24 months after hospital discharge. The primary outcome was a composite of death and major disability at the two-year follow-up visit. Mean SBP was reduced by 21.8 in the treatment group and 12.7 mm Hg in the control group within 24 hours after randomization (P<0.001). Mean SBP was 137.3 mm Hg in the treatment group and 146.5 in the control group at day 7 after randomization (P<0.001). At two-year follow-up, study outcomes were obtained in 1945 (95.4%) participants in the treatment group and 1925 (94.7%) in the control group. 78.8% of the patients in the treatment group and 72.6% in the control group reported the use of antihypertensive medications (p<0.001). SBP was 138.8 mmHg in the antihypertensive treatment group and 139.7 in the control group (p=0.02). Among patients in the antihypertensive treatment group, 24.5% (476/1945) died or had a major disability, compared with 22.1% (425/1925) in the control group (odds ratio 1.14 [95% CI 0.99 to 1.33], p=0.078). Hazard ratios for all-cause mortality (1.01 [0.81, 1.25], p=0.95), recurrent stroke (0.91 [0.73, 1.13], p=0.40), and vascular events (0.97 [0.79, 1.19], p=0.76) were not statistically significant comparing the antihypertensive treatment group to the control group. The effect of antihypertensive treatment did not differ by pre-defined subgroups. In conclusion, among patients with acute ischemic stroke, BP reduction with antihypertensive medications during hospitalization did not reduce or increase the composite outcome of death and major disability over two years.


Author(s):  
M. Angela O’Neal

This chapter discusses the evaluation and management of acute ischemic stroke in pregnancy. Stroke in pregnancy is rare, but is a significant cause of morbidity. The etiologies of stroke in pregnancy are diverse. The most common causes in hospital-based studies are cardioembolic or related to eclampsia. The use of intravenous tissue plasminogen activator (IV tPA) as well as intra-arterial clot retrieval in stroke have been validated by multiple trials. Small case series support the safety of both therapies in pregnancy. Therefore, the management of stroke in pregnancy should be based on the mechanism and severity of the stroke, not on obstetrical issues.


Author(s):  
Ji Y. Chong ◽  
Michael P. Lerario

Intravenous tissue plasminogen activator (IV tPA) is the mainstay of stroke therapy and is US Food and Drug Administration-approved for the treatment of acute ischemic stroke. Its benefit on functional outcome has been established in multiple randomized trials when administered within 3 hours. Select patients may be treated off-label up to 4.5 hours from symptom onset. Eligibility criteria need to be reviewed carefully to optimize benefit and to minimize complications, namely reperfusion hemorrhage.


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