Dataset Information

Development and validation of a penumbra-based predictive model for thrombolysis outcome in acute ischemic stroke patients.

ABSTRACT: The use of thrombolysis in acute ischemic stroke is restricted to a small proportion of patients because of the rigid 4·5-h window. With advanced imaging-based patient selection strategy, rescuing penumbra is critical to improving clinical outcomes. In this study, we included 155 acute ischemic stroke patients (84 patients in training dataset, age from 43 to 80, 59 males; 71 patients in validation dataset, age from 36 to 80, 45 males) who underwent MR scan within the first 9-h after onset, from 7 independent centers. Based on the mismatch concept, penumbra and core area were identified and quantitatively analyzed. Moreover, predictive models were developed and validated to provide an approach for identifying patients who may benefit from thrombolytic therapy. Predictive models were constructed, and corresponding areas under the curve (AUC) were calculated to explore their performances in predicting clinical outcomes. Additionally, the models were validated using an independent dataset both on Day-7 and Day-90. Significant correlations were detected between the mismatch ratio and clinical assessments in both the training and validation datasets. Treatment option, baseline systolic blood pressure, National Institutes of Health Stroke Scale score, mismatch ratio, and three regional radiological parameters were selected as biomarkers in the combined model to predict clinical outcomes of acute ischemic stroke patients. With the external validation, this predictive model reached AUCs of 0·863 as short-term validation and 0·778 as long-term validation. This model has the potential to provide quantitative biomarkers that aid patient selection for thrombolysis either within or beyond the current time window.

SUBMITTER: Tang TY

PROVIDER: S-EPMC6154778 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Development and validation of a penumbra-based predictive model for thrombolysis outcome in acute ischemic stroke patients.

Tang Tian-Yu TY Jiao Yun Y Cui Ying Y Zeng Chu-Hui CH Zhao Deng-Ling DL Zhang Yi Y Peng Cheng-Yu CY Yin Xin-Dao XD Gao Pei-Yi PY Yang Yun-Jun YJ Ju Sheng-Hong SH Teng Gao-Jun GJ

EBioMedicine 20180823

The use of thrombolysis in acute ischemic stroke is restricted to a small proportion of patients because of the rigid 4·5-h window. With advanced imaging-based patient selection strategy, rescuing penumbra is critical to improving clinical outcomes. In this study, we included 155 acute ischemic stroke patients (84 patients in training dataset, age from 43 to 80, 59 males; 71 patients in validation dataset, age from 36 to 80, 45 males) who underwent MR scan within the first 9-h after onset, from ...[more]

PMID: 30146341

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Project description:Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

Project description:Background: Hemorrhagic transformation (HT) after reperfusion therapy for acute ischemic stroke (AIS) has been well studied; however, there is scarce research focusing on spontaneous HT (sHT). Spontaneous HT is no less important with a relatively high incidence and could be associated with neurological worsening. We aimed to develop and validate a simple and practical model to predict sHT after AIS (SHAIS) and compared the predictive value of the SHAIS score against the models of post-Reperfusion HT for sHT. Methods: Patients with AIS admitted within 24 h of onset were prospectively screened to develop and validate the SHAIS score. The primary outcome was sHT during hospitalization (within 30 days after onset), and the secondary outcomes were symptomatic sHT and parenchymal hematoma (PH). Clinical information, laboratory, and neuroimaging data were screened to construct the SHAIS score. We selected six commonly used scales for predicting HT after reperfusion therapy and compared their predictive ability for sHT with the SHAIS score using Delong's test. Results: The derivation cohort included 539 patients (mean age, 68.1 years; men, 61.4%), of whom 91 (16.9%) patients developed sHT with 25.3% (23/91) being symptomatic sHT and 62.6% (57/91) being PH. Five variables (atrial fibrillation, NIHSS score ≥ 10, hypodensity > 1/3 of middle cerebral artery territory, hyperdense artery sign, and anterior circulation infarction) composed the SHAIS score, which ranged from 0 to 11 points. The area under the receiver-operating characteristic curve (AUC) was 0.86 (95% CI 0.82-0.91, p < 0.001) for the overall sHT, 0.85 (95% CI 0.76-0.92, p < 0.001) for symptomatic sHT, and 0.89 (95% CI 0.85-0.94, p < 0.001) for PH. No evidence of miscalibration of the SHAIS score was found to predict the overall sHT (p = 0.19), symptomatic sHT (p = 0.44), and PH (p = 0.22). The internal (n = 245) and external validation cohorts (n = 200) depicted similar predictive performance compared to the derivation cohort. The SHAIS score had a higher AUC to predict sHT than any of the six pre-Existing models (p < 0.05). Conclusions: The SHAIS score provides an easy-to-use model to predict sHT, which could help providers with decision-making about treatments with high bleeding risk, and to counsel patients and families on the baseline risk of HT, aligning expectations with probable outcomes.

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Dataset Information

Development and validation of a penumbra-based predictive model for thrombolysis outcome in acute ischemic stroke patients.

Publications

Development and validation of a penumbra-based predictive model for thrombolysis outcome in acute ischemic stroke patients.

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