Dataset Information

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

ABSTRACT: Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. Methods: We performed a post-hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Results: Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Conclusion: Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.

SUBMITTER: Jensen M

PROVIDER: S-EPMC7483750 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Jensen Märit M Schlemm Eckhard E Cheng Bastian B Lettow Iris I Quandt Fanny F Boutitie Florent F Ebinger Martin M Endres Matthias M Fiebach Jochen B JB Fiehler Jens J Galinovic Ivana I Thijs Vincent V Lemmens Robin R Muir Keith W KW Nighoghossian Norbert N Pedraza Salvador S Simonsen Claus Z CZ Gerloff Christian C Thomalla Götz G

Frontiers in neurology 20200828

Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. Methods: We performed a post-hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled ...[more]

PMID: 32982951

Similar Datasets

Project description:Importance:The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective:To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants:This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures:The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results:Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance:While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.

Project description:Background and objectivesCerebral microbleeds (CMBs) are common in patients with acute ischemic stroke 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 prespecified analysis of the prospective randomized controlled multicenter Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial including patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging-fluid-attenuated inversion recovery 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 IV thrombolysis with alteplase at 0.9 mg/kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by 3 raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale (mRS) score ≤1, and symptomatic ICH according to National Institutes of Neurological Disease and Stroke 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. Ninety-eight (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB; 37 (8.1%) had 2 to 4 CMBs; and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a nonsignificant increased risk of symptomatic ICH (11.2% vs 4.2%; adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.99-5.43, p = 0.052) but had no effect on functional outcome at 90 days (mRS score ≤1: 45.8% vs 50.7%; adjusted OR 0.99, 95% CI 0.59-1.64, p = 0.955). Patients receiving alteplase had better functional outcome (mRS score ≤1: 54.6% vs 44.6%, adjusted OR 1.61, 95% CI 1.07-2.43, p = 0.022) without evidence of heterogeneity in relation to CMB presence (p of the interactive term = 0.546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy related) or not strictly lobar CMB distribution.DiscussionIn the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in patients with acute ischemic stroke with ≥1 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 registration informationClinicalTrials.gov identifier NCT01525290; ClinicalTrialsRegister.EU identifier 2011-005906-32.Classification of evidenceThis study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.

Project description:Background and Purpose: Hyperhomocysteinemia (Hhcy) is a well-known risk factor for ischemic stroke. However, the role of Hhcy in the clinical outcome of ischemic stroke has not been fully elucidated. In addition, previous studies have found that Hhcy was implicated in the disruption of the blood-brain barrier, which may increase the risk of hemorrhagic transformation (HT) after thrombolysis. Thus, the aim of this study was to investigate the effect of Hhcy on the clinical outcome and HT after thrombolysis in ischemic stroke patients. Methods: Patients who were diagnosed with ischemic stroke and received intravenous thrombolytic therapy between January 2016 and September 2018 were included in this study. Multivariate logistic regression analysis was used to assess the association between Hhcy, clinical outcome, and HT after thrombolysis. Furthermore, the potential interaction between Hhcy and hypertension on the clinical outcome and HT after thrombolysis was also assessed. Results: Of 568 patients, 455 (80.1%) had Hhcy, 66 (11.6%) had HT, and 219 (38.6%) had poor outcome. Patients with Hhcy had a higher incidence of poor outcome than the patients with non-Hhcy (40.9 vs. 29.2%, p = 0.022). However, there was no significant difference in the incidence of HT (11.9 vs. 10.6%, p = 0.711) between patients with Hhcy and non-Hhcy. After adjustment for major covariates, multivariate logistic regression analysis disclosed that Hhcy was independently associated with increased risk of poor outcome (OR = 1.760; 95% CI: 1.069-2.896) but was not associated with the risk of HT (OR = 1.017; 95% CI: 0.495-2.087). In addition, we found no significant interaction between Hhcy and hypertension on the clinical outcome (p = 0.513) or HT (p = 0.170) after thrombolysis. Conclusion: We found that Hhcy was an independent risk factor for poor outcome, but not an independent risk factor for HT after thrombolysis in ischemic stroke patients. In addition, there was no significant interaction of Hhcy and hypertension on the clinical outcome or HT after thrombolysis.

Project description:BackgroundHemorrhagic transformation (HT) is the most serious complication of ischemic stroke patients after intravenous thrombolysis and leads to a poor clinical prognosis. This study aimed to determine the independent predictors associated with HT in stroke patients with intravenous thrombolysis and to establish and validate a nomogram that combines with predictors to predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.MethodThis study enrolled ischemic stroke patients with intravenous thrombolysis from December 2016 to June 2022. All the patients were divided into training and validation cohorts. The nomogram was composed of the significant predictors for HT in the training cohort as obtained by the multivariate logistic regression analysis. The area under the receiver operating characteristic curve was used to assess the discriminative performance of the nomogram. The calibration performance of the nomogram was assessed by the Hosmer-Lemeshow goodness-of-fit test and calibration plots. Decision curve analysis was used to test the clinical validity of the nomogram.ResultsA total of 394 patients with intravenous thrombolysis were enrolled in the study. In the training cohort (n = 257), 45 patients had HT after intravenous thrombolysis. Multivariate logistic regression analysis demonstrated early infarct signs (OR, 7.954; 95% CI, 3.553-17.803; P < 0.001), NIHSS scores (OR, 1.110; 95% CI, 1.054-1.168; P < 0.001), uric acid (OR, 0.993; 95% CI, 0.989-0.997; P = 0.001), and albumin-to-globulin ratio (OR, 0.109; 95% CI, 0.023-0.508; P = 0.005) were independent predictors for HT and constructed the nomogram. In the training and validation cohorts, the AUC of the nomogram was 0.859 and 0.839, respectively. The Hosmer-Lemeshow goodness-of-fit test and calibration plot showed good concordance between predicted and observed probability in the training and validation cohorts. Decision curve analysis indicated that the nomogram was significantly useful for predicting HT in the training and further confirmed in the validation cohort.ConclusionThis study proposes a novel and practical nomogram based on early infarct signs, NIHSS scores, uric acid, and albumin-to-globulin ratio that can well predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.

Dataset Information

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Publications

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets