Abstract WP103: Re-Examining the Exclusion Criterion of Early Recurrent Ischemic Stroke in Intravenous Thrombolysis: A Meta-Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Katrina Hannah Ignacio ◽  
Jose Danilo Diestro ◽  
Adrian Espiritu ◽  
Julian Spears ◽  
Maria Cristina San Jose

Background: Current guidelines for intravenous tissue plasminogen activator for acute ischemic stroke preclude the administration of the drug in patients with a history of recent stroke. Objectives: Our meta-analysis aims to determine the safety and efficacy of thrombolysis in patients with early recurrent ischemic stroke (within 3 months of initial stroke). Methods: Pubmed, Cochrane, Scopus, Embase, Clinicaltrials.gov , and HERDIN were searched for studies comparing the outcomes of acute stroke patients undergoing intravenous thrombolysis between those with early recurrent stroke (ERS) and those without. Random-effects meta-analysis was used to evaluate the outcomes in terms of symptomatic intracranial hemorrhage, mortality and good functional outcomes at 3 months (modified Rankin Score < 2 ) Results: Three observational studies with a total of 48,459 thrombolysed patients (824 with ERS and 47,635 without) were included in the study. There was no significant difference between patients with ERS and those without in terms of symptomatic intracranial hemorrhage (OR 1.39, 95% Confidence Interval [CI] 0.75-2.58), mortality (OR 1.36, 95% CI 0.60-3.09) and good functional outcomes at 3 months (OR 0.74, 95% CI 0.47-1.16). Conclusion: Our meta-analysis suggests that there is insufficient evidence to substantiate excluding patients with ERS from receiving thrombolysis. Further studies to re-examine ERS as an exclusion criterion for receiving thrombolysis are warranted.

Author(s):  
Huijuan Li ◽  
Ying Xian ◽  
Daniel Laskowitz ◽  
Eric Peterson

Background and Purpose: The risk for bleeding complications after intravenous thrombolysis for ischemic stroke in patients on warfarin with international normalized ratio [INR] ≤1.7) remains unclear. The aim of the current study is to perform a meta-analysis to determine whether there is an association between warfarin and risk of symptomatic intracranial hemorrhage (sICH). Methods: We searched MEDLINE, Web of Science and EBSCO databases for articles published through Jul 2012. A random-effects model was used to compute the pooled risk estimate. Results: Overall, 11 observational studies were identified that met our study inclusion criteria. This included 29,283 stroke participants treated with tPA; of which 2129 (7.3%) patients were on home warfarin prior treatment. Warfarin pretreatment was associated with an increased crude OR for symptomatic intracranial hemorrhage (sICH) (combined OR=1.77; 95% CI, 1.07~2.93;P=0.03).Of these studies, 7 studies had conducted a multivariate adjusted analyses, which demonstrated no association between warfarin use and increased risk of sICH following tPA use (combined adjusted OR=1.73; 95% CI, 0.91-3.28; p=0.10). Conclusions: These data suggested that the risk of sICH after thrombolytic therapy is not increased in patients using warfarin with sub therapeutic INR levels.


2021 ◽  
Vol 26 (4) ◽  
pp. 671-683
Author(s):  
YinQin Hu ◽  
YangBo Hou ◽  
Zhen Chen ◽  
Qian Xiao ◽  
Huixia Chen ◽  
...  

Background: Intravenous thrombolysis is the preferred clinical treatment for acute ischemic stroke. Alteplase is an intravenous thrombolytic drug used in clinical practice. Recently, studies have shown the efficacy of another intravenous thrombolytic drug, tenecteplase, and have reported that the risk of bleeding is low. However, at present, Chinese and international research has yielded controversial results regarding the efficacy and risks of tenecteplase. Therefore, this systematic review and meta- analysis of the efficacy and safety of tenecteplase were performed. Methods: PubMed, the Cochrane Library, MEDLINE, the Wanfang Database and CNKI were searched for all studies on the thrombolytic treatment of acute ischemic stroke. All studies published in English prior to March 2021 were retrieved. The studies were screened and selected based on the inclusion and exclusion criteria. Then, the data were extracted and recorded by trained researchers. RevMan 5.4 statistical software was used to analyze the data on the 24h recanalization rate, early neurological improvement (24h reduction in the National Institutes of Health Stroke Scale [NIHSS] score of at least 8 points or 24 h NIHSS score of 0~1 point), mRS score at 90 days, intracranial hemorrhage, symptomatic intracranial hemorrhage and mortality in the tenecteplase group and alteplase group. Results: A total of 565 related studies were identified through the initial searches in each database. The citations of meta-analyses and related reviews were screened for additional eligible articles. Eventually, 9 high-quality English-language articles that included 2149 patients with acute ischemic stroke (including 1035 in the tenecteplase group and 1046 in the alteplase group)were included in this meta-analysis. The meta-analysis results were as follows: (1) Efficacy: The 24 h recanalization rate with regard to vascular recanalization was significantly better in the tenecteplase group than in the alteplase group(OR = 1.83, 95% CI: 1.23~2.72, z = 2.97, P = 0.003). There was significantly greater improvement in early neurological function in the tenecteplase group than in the alteplase group (OR= 1.34, 95% CI: 1.11~1.63, Z=3.00, P =0.003). There were no significant differences in 90-day mRS scores between the two groups (mRS score =0-1, OR = 1.20, 95% CI: 0.99~1.46, z = 1.82, p = 0.07; mRS score =0-2, OR = 1.17, 95% CI: 0.94~1.45, z = 1.38, p = 0.17). However, the subgroup analysis showed that the 90-day mRS score of the 0.25 mg/kg tenecteplase group was significantly different from that of groups treated with other doses of tenecteplase (OR = 1.48, 95% CI: 1.01~2.03, z = 2.03, p = 0.04). (2) Safety: The incidences of any intracranial hemorrhage (OR = 0.91, 95% Ci: 0.55~1.49, z = 0.39, p = 0.70), symptomatic intracranial hemorrhage (OR = 1.21, 95% CI: 0.63~2.32, z = 0.56 P = 0.57), and mortality (OR = 0.85, 95% CI: 0.57~1.26, z = 0.82, p = 0.41) were not significantly different between the tenecteplase and alteplase groups. Conclusions: Tenecteplase can significantly increase the 24-hour vascular recanalization rate and improve the neurological prognosis of patients with acute ischemic stroke and it does not increase the risk of intracranial hemorrhage or mortality.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Reza Bavarsad Shahripour ◽  
Benjamin Shifflett ◽  
Edward Labin ◽  
Morgan Figurelle ◽  
Anna Barminova ◽  
...  

Background: Patients with acute ischemic stroke (AIS) due to atrial fibrillation (afib) may have increased complications from intravenous thrombolysis or endovascular treatment (ET) compared to other stroke subtypes. The purpose of this study was to compare the rates of symptomatic intracranial hemorrhage (sICH) in patients with and without a history of a fib treated with IV rt-PA and/or ET. Methods: Consecutive stroke code activations were retrospectively analyzed from January 2004-June 2020 at an academic comprehensive stroke center. Patients were included if they were treated with IV rt-PA and/or ET within 24 hours of stroke onset. Patients were stratified into the six groups:1-No hx of a fib with ET only, 2-Hx of a fib with ET only, 3-No hx of a fib with IV rt-PA plus ET, 4-Hx of a fib with IV rt-PA plus ET, 5-No hx of a fib with IV rt-PA only, 6-Hx of a fib with IV rt-PA only. Primary outcome was defined as any sICH within 72 hours of treatment using the NINDS definition. Baseline demographics were compared. Chi squared was used to assess differences in sICH rates and logistic regression to compare individual groups. Analyses were both unadjusted and adjusted for baseline NIHSS, age, sex, baseline blood pressure, pre-stroke mRS, smoking status, and baseline glucose. Results: We identified 720 AIS patients who received acute treatment (IV rt-PA: n=578; ET: n=100; IV rt-PA+ET:n=18). There was a significant difference in sex (p=0.005); Hispanic ethnicity (p=0.002); current smoking (p=<0.001); current alcohol use (p=0.03), CHF (p=0.01); and age (p<0.0001) between groups. Baseline NIHSS was significantly higher in Group 4 (23, SD 8, p=<0.001).In adjusted analysis, there was no significant difference in sICH in patients with a fib after receiving IVtPA (OR 1.53, CI 0.47-4.99, p=0.48), ET (OR 0.93 , CI 0-∞, p=1.00), or both (OR 0.25,CI 0.00-9.07, p=0.45) compared to those without afib. There was no significant difference in sICH in adjusted analyses in patients with and without a fib overall (OR 0.93, CI 0-∞, p=1.00). Conclusion: In this study, atrial fibrillation did not have a significant impact on rates of sICH in AIS patients treated with IV rt-PA, ET, or both. This study supports the safety of IV rt-PA, ET, and combination therapy in the atrial fibrillation population.


Neurology ◽  
2020 ◽  
Vol 95 (2) ◽  
pp. e121-e130
Author(s):  
Konark Malhotra ◽  
Aristeidis H. Katsanos ◽  
Nitin Goyal ◽  
Ashis Tayal ◽  
Henrik Gensicke ◽  
...  

ObjectiveTo determine the association of chronic kidney disease (CKD) with the safety and efficacy of IV thrombolysis (IVT) among patients with acute ischemic stroke (AIS).MethodsA systematic review and pairwise meta-analysis of studies involving patients with CKD undergoing IVT for AIS were conducted to evaluate the following outcomes: symptomatic intracranial hemorrhage (sICH), asymptomatic and any intracranial hemorrhage (ICH), in-hospital and 3-month mortality, 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] score 0–1), and 3-month functional independence (FI, mRS score 0–2). CKD was defined with estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60–89 mL/min) to moderate (eGFR 30–59 mL/min) to severe (eGFR 15–29 mL/min).ResultsWe identified 20 studies comprising 60,486 patients with AIS treated with IVT. In unadjusted analyses, CKD was associated with sICH according to the National Institute of Neurological Disorders and Stroke (NINDS) (7 studies; odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67) and European Cooperative Acute Stroke Study (ECASS) II (9 studies; OR 1.37, 95% CI 1.01–1.85) definitions, any ICH (8 studies; OR 1.42, 95% CI 1.18–1.70), 3-month mortality (9 studies; OR 2.20, 95% CI 1.72–2.81), 3-month FFO (8 studies; OR 0.58, 95% CI 0.47–0.72), and 3-month FI (8 studies; OR 0.57, 95% CI 0.46–0.71). In adjusted analyses, CKD was associated with sICH according to NINDS (4 studies; ORadj 1.34, 95% CI 1.01–1.79) and ECASS II (3 studies; ORadj 2.08, 95% CI 1.27–3.43) definitions, any ICH (6 studies; ORadj 1.41, 95% CI 1.01–1.97), in-hospital mortality (2 studies; ORadj 1.19, 95% CI 1.09–1.30), and 3-month FFO (6 studies; ORadj 0.80, 95% CI 0.70–0.92).ConclusionsAfter adjustment for confounders in this pairwise meta-analysis, moderate to severe CKD is associated with increased risks of ICH and worse functional outcomes among patients with AIS treated with IVT.


Author(s):  
Houwei Du ◽  
Hanhan Lei ◽  
Gareth Ambler ◽  
Shuangfang Fang ◽  
Raoli He ◽  
...  

Background Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta‐analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke. Methods and Results We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90‐day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta‐analysis of randomized controlled trial and observational data revealed similar 90‐day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90–1.19), mortality (OR, 1.03; 95% CI, 0.78–1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76–1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51–0.91; P =0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61–0.84; P <0.001). Conclusions In this meta‐analysis of patients with acute ischemic stroke, we found no significant differences in 90‐day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy. Registration URL: https://www.crd.york.ac.uk/prospero/ ; Unique identifier: 42021234664.


2021 ◽  
Vol 19 ◽  
Author(s):  
Xiaohua Xie ◽  
Jie Yang ◽  
Lijie Ren ◽  
Shiyu Hu ◽  
Wancheng Lian ◽  
...  

Background: Symptomatic intracranial hemorrhage (sICH) is a serious hemorrhagic complication after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. Most existing predictive scoring systems were derived from Western countries Objective: To develop a nomogram to predict the possibility of sICH after IVT in an Asian population. Methods: This retrospective cohort study included AIS patients treated with recombinant tissue plasminogen activator (rt-PA) in a tertiary hospital in Shenzhen, China, from January 2014 to December 2020. The end point was sICH within 36 hours of IVT treatment. Multivariable logistic regression was used to identify risk factors of sICH, and a predictive nomogram was developed. Area under the curve of receiver operating characteristic curves (AUC), calibration curve, and decision curve analyses were performed. The nomogram was validated by bootstrap resampling Results: Data on a total of 462 patients were collected, of whom 20 patients (4.3%) developed sICH. In the multivariate logistic regression model, the National Institute of Health stroke scale scores (NIHSS) (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06–1.23, P < 0.001), onset to treatment time (OTT) (OR, 1.02; 95% CI, 1.01–1.03, P < 0.001), neutrophil to lymphocyte ratio (NLR) (OR, 1.22; 95% CI, 1.09–1.35, P < 0.001), and cardioembolism (OR, 3.74; 95% CI, 1.23–11.39, P = 0.020) were independent predictors for sICH and were used to construct a nomogram. Our nomogram exhibited favorable discrimination ability [AUC, 0.878; specificity, 87.35%; and sensitivity, 73.81%]. Bootstrapping for 500 repetitions was performed to further validate the nomogram. The AUC of the bootstrap model was 0.877 (95% CI: 0.823–0.922). The calibration curve exhibited good fit and calibration. The decision curve revealed good positive net benefits and clinical effects Conclusion: The nomogram consisted of the predictors NIHSS, OTT, NLR, and cardioembolism could be used as an auxiliary tool to predict the individual risk of sICH in Chinese AIS patients after IVT. Further external verification among more diverse patient populations is needed to demonstrate the accuracy of the model’s predictions.


2020 ◽  
Vol 26 ◽  
pp. 107602962094259
Author(s):  
Xiaolin Zhu ◽  
Genmao Cao

Background: Endovascular therapy and intravenous thrombolysis with recombinant tissue plasminogen activator are the 2 most recommended treatments for acute ischemic stroke (AIS). Glycoprotein (GP) IIb-IIIa inhibitors are short-acting selective reversible antiplatelet agents that emerged as promising therapeutic agents for AIS about 10 years ago. Given the unclear safety profile and application coverage of GP inhibitors, we conducted this meta-analysis to explore the same. Methods: We used GP IIb-IIIa inhibitors, intracranial hemorrhage, and mortality as the key words on Medline, Web of Science, and the Embase databases. Randomized controlled trials, prospective literatures, and retrospective studies in English published between 1990 and 2020 were screened. The outcomes were relative risk (RR) of death and 90-day intracerebral hemorrhage (ICH). We pooled the results in 2 categories and conducted a subgroup analysis stratified by different drugs. The choice of the effects model depended on the value of I 2. Results: In all, 3700 patients from 20 studies were included. No GP IIb-IIIa inhibitors were found to have a remarkable influence on the ICH rate. The RR values of symptomatic ICH for abciximab and eptifibatide were 4.26 (1.89, 9.59) and 0.17 (0.04, 0.69), respectively. Both tirofiban and abciximab could decrease the mortality rate within 90 days. Age > 70 years, National Institutes of Health Stroke Scale > 15, and overall dose > 10 mg are risk factors for ICH events with tirofiban usage. Thrombectomy combined with tirofiban was safe for arterial reocclusion prevention. Conclusions: In stroke-related treatment, administration of GP IIb-IIIa inhibitors could be safe, but care should be taken regarding drug species and doses. Abciximab can increase the risk of symptomatic intracranial hemorrhage. Tirofiban and eptifibatide can be considered safe in low doses. Suitable patients should be selected using strict criteria.


2021 ◽  
Vol 9 (3) ◽  
pp. 166-176
Author(s):  
Jia Feng ◽  
Zhihan Zhu ◽  
Ahmed Waqas ◽  
Lukui Chen

Objective:To evaluate whether endovascular thrombectomy combined with intravenous thrombolysis is superior to the standard treatment of intravenous thrombolysis for the treatment of ischemic stroke.Methods:A meta-analysis of 12 studies obtained by searching PubMed and Web of Science database was performed to determine whether the difference in mortality (within 7 days or 90 days), functional outcome (modified Rankin Scale, 0-2), hemorrhage (symptomatic intracerebral hemorrhage, and subarachnoid hemorrhage), and recurrent ischemic stroke rate at 90 days between patients who underwent mechanical intravenous thrombolysis with (intervention) and without (control) endovascular thrombectomy.Results:As compared with the control group, patients in the intervention group had lower 90-day mortality [summary risk ratio (RR) = 0.83, 95% confidence interval (CI): 0.69-0.99; n = 1309/1070], higher recanalization rate (RR = 2.24, 95% CI: 1.97-2.56; n = 504/497), better functional outcome (modified Rankin score: 0-2; RR = 1.41, 95% CI: 1.29-1.54; n = 1702/1502), and higher rate of subarachnoid hemorrhage (RR = 2.40, 95% CI: 1.45-3.99; n = 1046/875) without significant difference in the 7-day mortality (RR = 1.12, 95% CI: 0.84-1.50; n = 951/773), symptomatic intracranial hemorrhage (RR = 1.12, 95% CI: 0.82-1.54; n = 1707/1507), or recurrent ischemic stroke (RR = 0.90, 95% CI: 0.52-1.54; n = 718/506).Conclusion:Our results demonstrated that patients in the intervention group had lower mortality and better functional outcomes than the control group. Although patients in the intervention group had a higher rate of subarachnoid hemorrhage; hence, endovascular thrombectomy combined with intravenous thrombolysis is still a beneficial intervention for a defined population of stroke patients.


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