scholarly journals Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013055
Author(s):  
Ludwig Schlemm ◽  
Tim Bastian Braemswig ◽  
Florent Boutitie ◽  
Jan Vynckier ◽  
Märit Jensen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Treatment Effect ◽  
Intravenous Thrombolysis ◽  
Stroke Patients ◽  
Randomized Controlled ◽  
Link Type ◽  
Increased Risk ◽  
Search Trial

Background and ObjectivesCerebral microbleeds (CMBs) are common in acute ischemic stroke patients and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown.MethodsWe performed a pre-specified analysis of the prospective randomized controlled multicenter WAKE-UP trial including patients with acute ischemic stroke with unknown time of symptom onset and DWI-FLAIR mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with intravenous thrombolysis with alteplase at 0.9 mg / kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by three raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale score (mRS)≤1, and symptomatic intracerebral hemorrhage (ICH) according to NINDS trial criteria 22 to 36 hours after treatment.ResultsOf 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis; 98 (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB, 37 (8.1%) had 2-4 CMBs, and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a non-significant increased risk of symptomatic ICH (11.2% versus 4.2%; adjusted odds ratio 2.32 [95% CI 0.99-5.43]; P=.052), but had no effect on functional outcome at 90 days (mRS≤1: 45.8% versus 50.7%; adj. OR 0.99 [0.59-1.64]; P=.955). Patients receiving alteplase had better functional outcome (mRS≤1: 54.6% versus 44.6%, adj. OR 1.61 [1.07-2.43], P=.022) without evidence of heterogeneity in relation to CMB presence (P value of the interactive term .546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy-related) or non-strictly-lobar CMB distribution.DiscussionIn the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in acute ischemic stroke patients with one or more CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm-ratio in patients with a larger number of CMBs.Trial registrationClinicalTrials.gov number, NCT01525290 (https://clinicaltrials.gov/ct2/show/NCT01525290); EudraCT number, 2011-005906-32 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005906-32/GB).Classification of EvidenceThis study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and DWI-FLAIR mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.

Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Intravenous Thrombolysis ◽  
The United States ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Increased Risk ◽  
Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

Meta-analysis of the Smoker’s Paradox in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment

2019 ◽  
Vol 21 (9) ◽  
pp. 1181-1188 ◽  
Author(s):  
Peng Zhang ◽  
Zhen-Ni Guo ◽  
Xin Sun ◽  
Yingkai Zhao ◽  
Yi Yang
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Functional Outcomes ◽  
Meta Analysis ◽  
Intravenous Thrombolysis ◽  
Cochrane Library ◽  
Stroke Patients ◽  
Good Functional Outcome

Abstract Introduction The existence of the smoker’s paradox is controversial and potential mechanisms have not been explained. We aimed to explore the association between cigarette smoking and functional outcome at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis (IVT) or endovascular treatment (EVT). Methods This meta-analysis was conducted in accordance with the PRISMA guidelines. Studies exploring the association between smoking and good functional outcome (modified Rankin Scale score ≤ 2) following IVT or EVT were searched via the databases of PubMed, Embase, and the Cochrane Library from inception to August 8, 2018. Information on the characteristics of included studies was independently extracted by two investigators. Data were pooled using a random-effects or fixed-effects meta-analysis according to the heterogeneity of included studies. Results Among 20 identified studies, 15 reported functional outcomes following IVT, and five reported functional outcomes following EVT. Unadjusted analyses showed that smoking increased the odds of good functional outcomes with a pooled odds ratio (OR) of 1.48 (95% confidence interval [CI]: 1.36–1.60) after IVT and 2.10 (95% CI: 1.47–3.20) after EVT. Of IVT studies, only eight reported outcomes adjusted for covariates and none of the EVT studies reported adjusted outcomes. After adjustment, the relation between smoking and good functional outcome following IVT lost statistical significance (OR 1.14 [95% CI: 0.81–1.59]). Conclusion Our meta-analysis suggested that smoking was not associated with good functional outcome (mRS ≤ 2) at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis. Implications The existence of the smoker’s paradox is controversial. A previous letter by Plas et al. published in 2013 reported a positive result for the association between smoking and good functional outcome at 3 months in acute ischemic stroke patients who received intravenous thrombolysis (IVT). However, a major limitation of their meta-analysis was that the process of data synthesis was based on unadjusted data. Therefore, we conducted this meta-analysis to investigate the association based on adjusted data and a larger sample size. Our meta-analysis suggested that smoking was not associated with good functional outcome after adjusting for covariates.

Abstract WP262: Intravenous Thrombolysis in Acute Ischemic Stroke Patients With Infective Endocarditis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mangala Gopal ◽  
Sushil Lakhani ◽  
Vivien Lee
Keyword(s):  
Ischemic Stroke ◽  
Infective Endocarditis ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Intravenous Thrombolysis ◽  
Stroke Patients ◽  
Medical Risk ◽  
Good Functional Outcome ◽  
Intravenous Tissue Plasminogen Activator ◽  
The Mean

Introduction: Infective endocarditis (IE) is considered to be an absolute contraindication for intravenous tissue plasminogen activator treatment (IVtPA) in acute ischemic stroke. However during the hyperacute stroke evaluation, the exclusion of IE may be difficult. Methods: We reviewed consecutive patients hospitalized at our comprehensive stroke center from January 1, 2014 to March 31, 2019 with acute ischemic stroke who received IVtPA and identified patients who were diagnosed with infective endocarditis. Data was abstracted on demographics, medical history, clinical presentation, last known normal (LKN) time, initial National Institutes of Health Stroke Scale (NIHSS), neuroimaging, culture results, and 90 day modified Rankin Scale (mRS). Good functional outcome was defined as mRS ≤ 2. Results: Among 1022 acute ischemic stroke patients who received IVtPA, 5 patients (0.5%) were ultimately diagnosed with IE. Among the 5 patients with IE, the mean age was 53.4 years (range, 25-74) and 3 (60%) were female. The majority, 4 (80%) were white. Medical risk factors for IE were present in 3 (60%) and included intravenous drug use (1) and dialysis (2). Initial NIHSS was 4.6 (range, 1 to 8). Fever was present on initial presentation in only 1 patient (102.7 F). All patients met criteria for IVtPA and there were no protocol violations. The mean time from LKN to IVtPA was 3.0 hours (range, 1.9 to 4.4). Vascular imaging showed MCA occlusion in 4 (80%) and no occlusion in 1 (20%). One patient underwent endovascular thrombectomy with Thrombolysis in cerebral infarction scale 2A recanalization. Two patients (40%) developed hemorrhagic complications, including 1 patient who developed subarachnoid hemorrhage on Hospital Day #2 due to mycotic cerebral aneurysm. The blood culture results included MRSE (1), Streptococci viridans (2) and negative (2). TEE in all patients showed vegetations on the mitral valve. No patients had good functional outcome, and the mean 3 months mRS was 4.8 (range, 3 to 6). Conclusions: In a large series of acute ischemic stroke patients who received IVtPA, undiagnosed IE is rare (0.5%). Fever was not commonly present during initial evaluation. Despite affecting younger patients with initial mild deficits, patients with IE had poor functional outcomes.

scholarly journals Outcome of intravenous thrombolysis for acute ischemic stroke in patients with and without atrial fibrillation

2017 ◽  
Vol 70 (7-8) ◽  
pp. 203-208
Author(s):  
Zeljko Zivanovic ◽  
Dragan Adamovic ◽  
Aleksandra Lucic-Prokin ◽  
Timea Kokai-Zekic ◽  
Jelena Sekaric ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intravenous Thrombolysis ◽  
Binary Logistic Regression ◽  
Neurological Status ◽  
Stroke Patients ◽  
Severe Stroke ◽  
Increased Risk ◽  
Favorable Clinical Outcome

Introduction. Atrial fibrillation is associated with an increased risk of ischemic stroke. The benefit of intravenous thrombolysis in patients with acute ischemic stroke and atrial fibrillation is still unclear. The aim of the study was to assess and compare the effects of intravenous thrombolysis in stroke patients with and without atrial fibrillation. Material and Methods. We analyzed stroke patients who were treated with intravenous thrombolysis. Patients were divided into two groups according to the presence of atrial fibrillation. Demographic, clinical and radiological characteristics of patients were compared between the two groups. The treatment efficacy was evaluated in relation to the improvement of neurological status after 24 hours, and functional recovery after three months. Binary logistic regression was used to evaluate predictors of outcome. Results. From a total of 188 patients, 39.4% presented with atrial fibrillation. Patients with atrial fibrillation were older (69.4 vs. 62.6 years; p <0.0001), with female predominance (43.2% vs. 28.9%, p = 0.04) and had clinically more severe stroke (National Institutes of Health Stroke Scale, score on admission 15.4 vs. 12.1; p = 0.0001). Significantly more patients without atrial fibrillation (61.4% vs. 43.2%, p = 0.01) had a favorable clinical outcome at three months after stroke. Nevertheless, atrial fibrillation was not an independent predictor of poor outcome at three months after stroke (p=0.66). Conclusion. Acute ischemic stroke patients, with atrial fibrillation, treated with intravenous thrombolysis, had worse outcomes than patients without atrial fibrillation did. However, it is mainly due to older age and a more severe stroke in patients with atrial fibrillation.

scholarly journals Prognostic Value of Neutrophil To Lymphocyte Ratio In Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis: A Meta-Analysis

2021 ◽  
Author(s):  
Chengbing Wang ◽  
Qian Zhang ◽  
Mingwei Ji ◽  
Jing Mang ◽  
Zhongxin Xu
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Intravenous Thrombolysis ◽  
Poor Functional Outcome ◽  
Lymphocyte Ratio ◽  
Increased Risk ◽  
The Relationship

Abstract Background: The neutrophil to lymphocyte ratio (NLR) has been shown to be an important independent inflammatory indicator in stroke. The relationship between NLR and poor prognostics in acute ischemic stroke (AIS) patients who received intravenous thrombolysis (IVT) still unclear. The purpose of this meta-analysis was to evaluate the association between NLR and poor prognosis after IVT. Furthermore, we aim to concluded whether admission NLR or post-IVT NLR play a role in AIS.Methods: Pubmed, Embase, Wed of Science and China National Knowledge Infrastructure were searched for relevant articles until October 7, 2020. Cohort and case-control studies were included if related to NLR in AIS patients treated with IVT. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were pooled to estimate the relationship between NLR and poor prognosis after IVT. A random effects model was used to calculate the pooled data.Results: Twelve studies, including 3641 patients met the predefined inclusion criteria. Higher NLR levels were associated with an increased risk of hemorrhagic transformation (HT) (OR=1.33,95%CI=1.14-1.56, P<0.001) and 3-month poor functional outcome (OR=1.64,95%CI=1.38-1.94, P<0.001) in AIS patients receiving IVT. Subgroup analysis of HT suggested that admission NLR levels rather than post-IVT NLR levels was associated with higher risk of HT (OR=1.33,95%CI=1.01-1.75, P=0.039). But There had no statistically significant difference between higher NLR levels and 3-month mortality (OR=1.14, 95%CI=0.97-1.35, P=0.120).Conclusions: High NLR can predict HT and 3-month poor functional outcome in AIS patients received IVT. Admission NLR rather than post-IVT NLR was independent risk factor of increased risk of HT.

Abstract WP318: On Versus Off-Hour Intravenous Thrombolysis in Acute Ischemic Stroke Patients Treated via Telestroke- Impact on Long-Term Functional Outcome

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Eyad Almallouhi ◽  
Tarun Girotra ◽  
Deepak Reddy ◽  
Sami Al Kasab ◽  
Nancy Turner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Intravenous Thrombolysis ◽  
Stroke Patients

scholarly journals Benefit of Intravenous Thrombolysis in Acute Ischemic Stroke Patients With High Cerebral Microbleed Burden

Stroke ◽  
2020 ◽  
Vol 51 (1) ◽  
pp. 232-239 ◽  
Author(s):  
Ludwig Schlemm ◽  
Matthias Endres ◽  
David J. Werring ◽  
Christian H. Nolte
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Treatment Effect ◽  
Older Patients ◽  
Intravenous Thrombolysis ◽  
Modified Rankin Scale ◽  
Resonance Imaging ◽  
Stroke Patients ◽  
Treatment Delays ◽  
Point Estimates

Background and Purpose— Cerebral microbleeds (CMBs) are a risk factor for intracranial hemorrhage. Whether intravenous thrombolysis (IVT) improves functional outcome in acute ischemic stroke patients with CMBs is unknown. We aimed to estimate the treatment effect of IVT in patients with acute ischemic stroke and a high burden (>10) of CMBs. Methods— We devised a multistep algorithm to model 90-day modified Rankin Scale scores in patients with ≤10 versus >10 CMBs who do or do not receive IVT. Parameters were extracted from recently published meta-analyses and included pairwise relationships between CMBs, IVT, 3-month functional outcome, and intracranial hemorrhage. Uncertainty was quantified in probabilistic sensitivity analyses. Results— In patients with >10 CMBs as compared with ≤10 CMBs, point estimates of the odds ratios for favorable outcome (modified Rankin Scale ≤2) associated with IVT were 7% to 10% lower but still >1 (range, 1.03–1.51). On the other hand, IVT in patients with >10 CMBs significantly increased the odds of mortality. The point estimates for the net treatment effect of IVT (change in the utility-weighted modified Rankin Scale score) in patients with >10 CMBs were in favor of withholding IVT in older patients with more severe strokes and longer treatment delays. However, because the general pretest probability of >10 CMBs is low (0.6%–2.7%), pretreatment magnetic resonance imaging to quantify CMB burden would be justified only if it delayed IVT by <10 minutes. Conclusions— High CMB burden modifies the treatment effect of IVT. In patients with >10 CMBs, IVT is associated with higher mortality and, in older patients with severe strokes and longer treatment delays, a net utility loss. Patients with higher-than-average pretest probability of >10 CMB might profit from magnetic resonance imaging screening if it does not increase the treatment time.

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