Plasma S100A8/A9 Concentrations and Clinical Outcomes of Ischemic Stroke in 2 Independent Multicenter Cohorts

Abstract Background S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts. Methods Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events. Results Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66–2.68) for the primary outcome and 1.62 (95% CI, 1.27–2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10–8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38–3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%–39%; P < 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P < 0.001 for linearity). Subgroup analyses further confirmed these associations. Conclusions High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.

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Tissue inhibitor metalloproteinase-1 and clinical outcomes after acute ischemic stroke

Neurology ◽

10.1212/wnl.0000000000008389 ◽

2019 ◽

Vol 93 (18) ◽

pp. e1675-e1685 ◽

Cited By ~ 4

Author(s):

Chongke Zhong ◽

Guangli Wang ◽

Tan Xu ◽

Zhengbao Zhu ◽

Daoxia Guo ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Scale Score ◽

Primary Outcome ◽

Tissue Inhibitor ◽

Vascular Events ◽

Baseline Serum ◽

Hazard Ratios ◽

Increased Risk

ObjectiveTo prospectively investigate the relationships between serum tissue inhibitor metalloproteinase-1 (TIMP-1) and clinical outcomes in patients with acute ischemic stroke.MethodsWe derived data from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline serum TIMP-1 concentrations were measured in 3,342 participants. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke, and secondary outcomes included major disability, death, and vascular events.ResultsA total of 843 participants (25.2%) experienced major disability or died within 3 months. After adjustment for age, sex, admission NIH Stroke Scale score, and other important covariates, odds ratios or hazard ratios (95% confidence intervals) of 1-SD (0.17 ng/mL) higher log-TIMP-1 were 1.17 (1.06–1.29) for the primary outcome, 1.13 (1.02–1.25) for major disability, 1.49 (1.19–1.87) for death, and 1.34 (1.11–1.62) for the composite outcome of death and vascular events. The addition of serum TIMP-1 to conventional risk factors model significantly improved risk prediction of the primary outcome (net reclassification index 9.0%, p = 0.02; integrated discrimination improvement 0.2%, p = 0.03). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had the highest risk of all study outcomes.ConclusionsHigher TIMP-1 levels were associated with increased risk of mortality and major disability after acute ischemic stroke. Our findings provided evidence supporting the important prognostic role of extracellular matrix biomarkers after acute ischemic stroke.

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Increased Growth Differentiation Factor 15 Is Associated with Unfavorable Clinical Outcomes of Acute Ischemic Stroke

Clinical Chemistry ◽

10.1373/clinchem.2018.297879 ◽

2019 ◽

Vol 65 (4) ◽

pp. 569-578 ◽

Cited By ~ 5

Author(s):

Jieyun Yin ◽

Zhengbao Zhu ◽

Daoxia Guo ◽

Aili Wang ◽

Nimei Zeng ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Primary Outcome ◽

Stroke Recurrence ◽

Stroke Patients ◽

Vascular Events ◽

Baseline Serum ◽

Growth Differentiation Factor 15 ◽

Differentiation Factor

Abstract BACKGROUND Growth differentiation factor 15 (GDF-15), a stress-responsive biomarker, is known to be independently associated with mortality and cardiovascular events in different disease settings, but data on the prognostic value of GDF-15 after stroke are limited. METHODS Baseline serum GDF-15 was measured in 3066 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite of death and major disability within 3 months. Secondary outcomes included death, major disability, vascular events, and stroke recurrence. The associations between GDF-15 and clinical outcomes after stroke were assessed by multivariate logistic regression or Cox proportional hazards models. RESULTS At 3 months' follow-up, 676 (22.05%), 86 (2.80%), 81 (2.64%), and 51 (1.66%) patients had experienced major disability, death, vascular events, or stroke recurrence, respectively. After adjusting for age, sex, current smoking, alcohol consumption, and baseline National Institutes of Health Stroke Scale score, the odds ratio/hazard ratio (95% CI) of 1 SD higher of base-10 log-transformed GDF-15 was 1.26 (1.15–1.39) for primary outcome, 1.13 (1.02–1.25) for major disability, 1.79 (1.48–2.16) for death, and 1.26 (1.00–1.58) for vascular events. The addition of GDF-15 to established risk factors improved risk prediction of the composite outcome of death and major disability (c-statistic, net reclassification index, and integrated discrimination improvement, all P < 0.05). CONCLUSIONS High GDF-15 concentrations are independently associated with adverse clinical outcomes of acute ischemic stroke, suggesting that baseline serum GDF-15 could provide additional information to identify ischemic stroke patients at high risk of poor prognosis.

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Increased Serum Complement C3 Levels Are Associated With Adverse Clinical Outcomes After Ischemic Stroke

Stroke ◽

10.1161/strokeaha.120.031715 ◽

2021 ◽

Author(s):

Pinni Yang ◽

Zhengbao Zhu ◽

Yuhan Zang ◽

Xiaoqing Bu ◽

Tian Xu ◽

...

Keyword(s):

Ischemic Stroke ◽

Clinical Outcomes ◽

Primary Outcome ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Elevated Serum ◽

Complement C3 ◽

Serum Complement ◽

Vascular Events ◽

Increased Risk

Background and Purpose: Complement C3 has been implicated in inflammation and ischemia/reperfusion injury, but its impact on the prognosis of ischemic stroke remains unclear. Aim of this study was to prospectively investigate the association between serum complement C3 and adverse clinical outcomes after ischemic stroke. Methods: We measured serum complement C3 levels for 3474 patients with ischemic stroke in 26 participating hospitals and collected data of clinical outcomes at 3 months after ischemic stroke. The primary outcome was composite outcome of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset and secondary outcomes included major disability, death, and vascular events. Results: During 3 months of follow-up, 866 participants (25.4%) developed primary outcome. After multivariate adjustment, elevated serum complement C3 levels were associated with increased risk of primary outcome (odds ratio, 1.30 [95% CI, 1.02–1.65]; P trend =0.038) when 2 extreme tertiles were compared. Each SD increase of log-transformed complement C3 was associated with 13% (95% CI, 2%–25%) increased risk of primary outcome. Multivariable-adjusted spline regression model showed a linear relationship between serum complement C3 and the risk of primary outcome ( P linearity =0.022). Addition of serum complement C3 to conventional risk factors significantly improved the risk prediction of primary outcome (net reclassification index: 8.87%, P =0.028; integrated discrimination index: 0.19%, P =0.029). Conclusions: High serum complement C3 levels at baseline were associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that serum complement C3 may be a valuable prognostic biomarker for ischemic stroke.

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Non-contrast head CT alone for thrombectomy in acute ischemic stroke: analysis of the ANGEL-ACT registry

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2021-017940 ◽

2021 ◽

pp. neurintsurg-2021-017940

Author(s):

Zeguang Ren ◽

Gaoting Ma ◽

Maxim Mokin ◽

Ashutosh P Jadhav ◽

Baixue Jia ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Primary Outcome ◽

Ct Perfusion ◽

Non Invasive ◽

Vessel Imaging ◽

Baseline Characteristics ◽

Procedural Outcomes ◽

Head Computed Tomography

BackgroudThe goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT).MethodsThis is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0–1, 0–2, and 0–3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days.ResultsA total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, P<0.001). Patients in the NCHCT alone group showed a smaller increase in baseline mRS score at 90 days (median 3 vs 2 points; P=0.004) after adjustment. There were no significant differences between groups in the remaining clinical outcomes.ConclusionsIn patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

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Multiple biomarkers covering distinct pathways for predicting outcomes after ischemic stroke

Neurology ◽

10.1212/wnl.0000000000006717 ◽

2018 ◽

Vol 92 (4) ◽

pp. e295-e304 ◽

Cited By ~ 7

Author(s):

Chongke Zhong ◽

Zhengbao Zhu ◽

Aili Wang ◽

Tan Xu ◽

Xiaoqing Bu ◽

...

Keyword(s):

Ischemic Stroke ◽

Primary Outcome ◽

Prognostic Significance ◽

Complement C3 ◽

Vascular Events ◽

Net Reclassification Improvement ◽

Increased Risk ◽

Multiple Biomarkers ◽

Novel Biomarkers ◽

Integrated Discrimination Improvement

ObjectiveTo study the prognostic significance of multiple novel biomarkers in combination after ischemic stroke.MethodsWe derived data from the China Antihypertensive Trial in Acute Ischemic Stroke, and 12 informative biomarkers were measured. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke, and secondary outcomes included major disability, death, and vascular events.ResultsIn 3,405 participants, 866 participants (25.4%) experienced major disability or died within 3 months. In multivariable analyses, elevated high-sensitive C-reactive protein, complement C3, matrix metalloproteinase-9, hepatocyte growth factor, and antiphosphatidylserine antibodies were individually associated with the primary outcome. Participants with a larger number of elevated biomarkers had increased risk of all study outcomes. The adjusted odds ratios (95% confidence intervals) of participants with 5 elevated biomarkers were 3.88 (2.05–7.36) for the primary outcome, 2.81 (1.49–5.33) for major disability, 5.67 (1.09–29.52) for death, and 4.00 (1.22–13.14) for vascular events, compared to those with no elevated biomarkers. Simultaneously adding these 5 biomarkers to the basic model with traditional risk factors led to substantial reclassification for the combined outcome (net reclassification improvement 28.5%, p < 0.001; integrated discrimination improvement 2.2%, p < 0.001) and vascular events (net reclassification improvement 37.0%, p = 0.001; integrated discrimination improvement 0.8%, p = 0.001).ConclusionWe observed a clear gradient relationship between the numbers of elevated novel biomarkers and risk of major disability, mortality, and vascular events. Incorporation of a combination of multiple biomarkers observed substantially improved the risk stratification for adverse outcomes in ischemic stroke patients.

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Abstract 19892: Association Between Estimated-glomerular Filtration Rate and Clinical Outcomes at One Year After Acute Ischemic Stroke

Circulation ◽

10.1161/circ.132.suppl_3.19892 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

xiaoqing bu ◽

Yonghong Zhang ◽

Tan Xu ◽

Hao Peng ◽

Jing Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Confidence Interval ◽

Acute Ischemic Stroke ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Recurrent Stroke ◽

Vascular Events ◽

Hazard Ratios ◽

All Cause Mortality ◽

The Relationship

Introduction: The relationship between estimated-glomerular filtration rate (eGFR) and acute ischemic stroke outcomes remains controversial. Hypothesis: We aimed to evaluate the impact of eGFR on all-cause mortality, recurrent stroke, and vascular events in patients with acute ischemic stroke. Methods: 4036 patients with acute ischemic stroke recruited from 26 hospitals across China from August 2009 to May 2013 were included in our study. GFR was estimated by CKD-EPI equations based on serum creatinine and/or cystatin C (CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys). The Cox proportional hazards models were used to examine the relationship between declined eGFR and 1-year all-cause mortality, recurrent stroke, and vascular events. Declined eGFR was defined as <60 mL/min /1.73 m2. Results: Declined eGFR was present in 7.22% (n=281) of patients based on the CKD-EPIcr equation, 3.43% (n=119) based on the CKD-EPIcys equation, and 5.67% (n=170) based on the CKD-EPIcr-cys equation. Compared to patients with an eGFR ≥90 mL/min /1.73 m2, adjusted hazard ratios (95% confidence interval) for all-cause mortality associated with eGFR<60 mL/min /1.73 m2 were 1.68 (1.06 to 2.66, p=0.026), 2.29 (1.29 to 4.06, p=0.005), and 1.79 (1.08 to 2.98, p=0.024) using CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, respectively. For recurrent stroke, adjusted hazard ratios (95% confidence interval) were 0.90 (0.49 to 1.66, p=0.743), 0.60 (0.19 to 1.93, p=0.393), and 0.89 (0.40 to 1.95, p=0.762), respectively. For vascular events, adjusted hazard ratios (95% confidence interval) were 1.33 (0.81 to 2.19, p=0.266), 1.07 (0.46 to 2.47, p=0.880), and 1.31 (0.70 to 2.43, p=0.403), respectively. Conclusion: Our study indicates that declined eGFR is a strong independent risk factor for total mortality among patients with acute ischemic stroke. However, there is no association between low eGFR and recurrent stroke or vascular events among patients with acute ischemic stroke. In addition, the association of eGFR with all-cause mortality among patients with acute ischemic stroke is stronger when eGFR was calculated based on the CKD-EPIcys equation compared to CKD-EPIcr and CKD-EPIcr-cys equations.

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Increased Postoperative Fasting Glucose Is Associated With Unfavorable Outcomes in Patients Treated With Mechanical Thrombectomy Treatment

Frontiers in Neurology ◽

10.3389/fneur.2021.668363 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zongjie Shi ◽

Shunyuan Guo ◽

Jie Pan ◽

Chao Xu ◽

Yu Geng ◽

...

Keyword(s):

Clinical Outcomes ◽

Primary Outcome ◽

Mechanical Thrombectomy ◽

Fasting Glucose ◽

Independent Predictor ◽

Secondary Outcome ◽

Vessel Occlusion ◽

Glucose Levels ◽

Increased Risk ◽

Symptomatic Intracranial Hemorrhage

Background and objective: Hyperglycemia on admission was associated with worse clinical outcomes after mechanical thrombectomy (MT) of acute ischemic stroke (AIS). We evaluated whether increased postoperative fasting glucose (PFG) was also related to poor clinical outcomes in patients who underwent MT treatment.Methods: Consecutive patients with large vessel occlusion underwent MT in our center were included. Admission glucose and fasting glucose levels after MT treatment were evaluated. Primary outcome was 90-day unfavorable outcomes (modified Rankin Scale score of 3–6). Secondary outcome was the rate of symptomatic intracranial hemorrhage (sICH) after MT treatment. The association of PFG and 90-day clinical outcome after MT treatment was determined using logistic regression analyses.Results: One hundred twenty seven patients were collected. The median postoperative fasting glucose level was 6.27 mmol/L (IQR 5.59–7.62). Fourteen patients (11.02%) had sICH, and fifty-eight patients (45.67%) had unfavorable outcomes at 90-day after MT. After adjustment for potential confounding factors, PFG level was an independent predictor of 90-day unfavorable outcome (OR 1.265; 95% CI 1.017–1.575; p = 0.035) and sICH (OR 1.523; 95% CI 1.056–2.195; p = 0.024) after MT. In addition, older age, higher baseline NIHSS score, and higher postoperative NLR were also associated with unfavorable outcomes at 90-day after MT treatment.Conclusions: Increased PFG is associated with unfavorable outcomes at 90-day and an increased risk of sICH in patients underwent MT treatment.

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Influence of Living Alone or with a Spouse Only on the Short-Term Prognosis in Patients after an Acute Ischemic Stroke

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17218223 ◽

2020 ◽

Vol 17 (21) ◽

pp. 8223

Author(s):

Yohei Ishikawa ◽

Toru Hifumi ◽

Mitsuyoshi Urashima

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Odds Ratio ◽

Retrospective Cohort ◽

Primary Outcome ◽

Living Alone ◽

Secondary Outcome ◽

Cardiovascular Risks ◽

Stroke Patients ◽

Short Term

Background—This study aimed to explore whether living alone or with a spouse only affects the short-term prognosis of acute ischemic stroke patients. Methods—We conducted a retrospective cohort study of patients with a diagnosis of acute ischemic stroke from April 2014 to February 2019 in Japan. The primary outcome was defined as worsening by at least one grade on the modified Rankin Scale (mRS). The secondary outcome was set as the degree of worsening on the mRS. The outcomes were compared between three groups of patients: (1) those living alone (ALONE), (2) those living with their spouse only (SPOUSE), and (3) OTHERs. Results—In total, 365 patients were included in this study: 111 (30%) ALONE, 133 (36%) SPOUSE, and 121 (33%) OTHERs. Cardiogenic embolisms were observed more frequently in ALONE than in OTHERs. The primary outcome occurred in 88 (79.3%) patients in ALONE and in 96 (72.2%) patients in SPOUSE, both of which were higher than the 72 (59.5%) in OTHERs. After adjusting with 19 variables, the risk of worsening was higher in ALONE (odds ratio (OR): 2.90, 95% confidence interval (CI): 1.50–5.58) and SPOUSE (OR: 1.83, 95% CI: 1.00–3.33) compared with OTHERs. Conclusions—In patients with acute ischemic stroke, not only living alone but also living with a spouse only may be associated with a worse short-term prognosis, independent of other cardiovascular risks.

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Abstract 183: Effect of Statin in Acute Cardioembolic Stroke Patients Who Are not Indicated According to Current Guidelines

Stroke ◽

10.1161/str.48.suppl_1.183 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Hong-Kyun Park ◽

Beom Joon Kim ◽

Moon-Ku Han ◽

Jong-Moo Park ◽

Kyusik Kang ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Statin Therapy ◽

Cardioembolic Stroke ◽

Secondary Outcome ◽

Rank Test ◽

Stroke Recurrence ◽

Specific Recommendation ◽

Stroke Patients ◽

Vascular Events

Background: There is no specific recommendation on statin therapy for cardioembolic stroke (CES) patients in current stroke guidelines. We evaluated the effect of statin on major vascular events following acute ischemic stroke in patients with CES and no other indications for statin. Methods: Using a prospective multicenter stroke registry database, we identified acute ischemic stroke patients who were hospitalized between 2008 and 2015 and were categorized into CES according to the Trial of Org 10172 in Acute Stroke Treatment classification. Patients who had established indications for statin in accordance with the recent stroke guidelines were excluded. Primary outcome measure was a major vascular event, a composite of stroke recurrence, myocardial infarction and vascular death; and secondary outcome measures were stroke recurrence and all-cause death. We performed frailty model analysis to estimate hazard ratios (HRs) of statin therapy on outcomes accounting for variation in quality of care among centers. Stabilized inverse probability of treatment weighting method with propensity scores was used to remove baseline imbalances between statin users and non-users. Results: Of the 6124 CES patients, 2987 patients (male, 52%; mean age, 73±12 years) met the eligibility criteria; and 2125 (71%) of 2987 patients were on statin at discharge. Compared to the non-users, the statin users were more likely to arrive at hospitals later, have milder neurologic deficits at presentation, be on stain prior to index stroke and have hyperlipidemia and were less likely to have atrial fibrillation and occlusion of relevant cerebral arteries. During the median follow-up of 364 days, major vascular events were observed in 118 patients (5.6%) among the statin users and 177 patients (20.5%) among the non-users, respectively (p<0.001 on log rank test); the adjusted HR of statin therapy was 0.35 (95% confidence interval, 0.27-0.46). The adjusted HRs of statin therapy were 0.71 (0.49-1.04) for stroke recurrence and 0.55 (0.46-0.66) for all-cause death, respectively. Conclusion: This study suggests that statin therapy may reduce major vascular events and all-cause death in cardioembolic stroke patients without definite indications for statin.

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Predicting Clinical Outcomes After Thrombolysis Using the iScore

Stroke ◽

10.1161/strokeaha.113.001343 ◽

2013 ◽

Vol 44 (10) ◽

pp. 2755-2759 ◽

Cited By ~ 20

Author(s):

Gustavo Saposnik ◽

Mathew J. Reeves ◽

S. Claiborne Johnston ◽

Philip M.W. Bath ◽

Bruce Ovbiagele

Keyword(s):

Ischemic Stroke ◽

Confidence Interval ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Odds Ratio ◽

Primary Outcome ◽

Favorable Outcome ◽

Tissue Type ◽

Modified Rankin Scale ◽

Secondary Outcomes

Background and Purpose— The ischemic stroke risk score (iScore) is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. Our goal was to determine the ability of the iScore to estimate clinical outcomes after intravenous thrombolysis tissue-type plasminogen activator (tPA) in the Virtual International Stroke Trials Archive (VISTA). Methods— We applied the iScore ( www.sorcan.ca/iscore ) to patients with an acute ischemic stroke within the VISTA collaboration to examine the effect of tPA. We explored the association between the iScore (<200 and ≥200) and the primary outcome of favorable outcome at 3 months defined as a modified Rankin scale score of 0 to 2. Secondary outcomes included death at 3 months, catastrophic outcomes (modified Rankin scale, 4–6), and Barthel index >90 at 3 months. Results— Among 7140 patients with an acute ischemic stroke, 2732 (38.5%) received tPA and 711 (10%) had an iScore ≥200. Overall, tPA treatment was associated with a significant improvement in the primary outcome among patients with an iScore <200 (38.9% non-tPA versus 47.5% tPA; P <0.001) but was not associated with a favorable outcome among patients with an iScore ≥200 (5.5% non-tPA versus 7.6% tPA; P =0.45). In the multivariable analysis after adjusting for age, baseline National Institutes of Health Stroke Scale, and onset-to-treatment time, there was a significant interaction between tPA administration and iScore; tPA administration was associated with 47% higher odds of a favorable outcome at 3 months among patients with an iScore <200 (odds ratio, 1.47; 95% confidence interval, 1.30–1.67), whereas the association between tPA and favorable outcome among those with an iScore ≥200 remained nonsignificant (odds ratio, 0.80; 95% confidence interval, 0.45–1.42). A similar pattern of benefit with tPA among patients with an iScore <200, but not ≥200, was observed for secondary outcomes including death. Conclusions— The iScore is a useful and validated tool that helps clinicians estimate stroke outcomes. In stroke patients participating in VISTA, an iScore <200 was associated with better outcomes at 3 months after tPA.

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