Research
Original Investigation
A Simple Risk Index and Thrombolytic Treatment Response in Acute Ischemic Stroke Bruce Ovbiagele, MD, MSc, MAS; Mathew J. Reeves, BVSc, PhD; Mojdeh Nasiri, MD; S. Claiborne Johnston, MD, PhD; Philip M. Bath, MD, FRCPath, FRCP; Gustavo Saposnik, MD, MSc, FRCPC; for the VISTA-Acute Collaboration Steering Committee
IMPORTANCE The Stroke Prognostication using Age and the NIH Stroke Scale index, created by combining age in years plus a National Institutes of Health (NIH) Stroke Scale score of 100 or higher (and hereafter referred to as the SPAN-100 index), is a simple risk score for estimating clinical outcomes for patients with acute ischemic stroke (AIS). The association between this index and response to intravenous thrombolysis for AIS has not been properly evaluated.
Supplemental content at jamaneurology.com CME Quiz at jamanetworkcme.com and CME Questions page 932
OBJECTIVE To assess the relationship between SPAN-100 index status and outcome following treatment with intravenous thrombolysis for AIS. DESIGN, SETTING, AND PARTICIPANTS Using the Virtual International Stroke Trials Archive (VISTA) database, an international repository of clinical trials data, we assessed the SPAN-100 index among 7093 patients with AIS who participated in 4 clinical trials from 2000 to 2006. The SPAN-100 index is considered positive if the sum of the age and the NIH Stroke Scale (a 15-item neurological examination scale with scores ranging from 0 to 42, with higher scores indicating more severe strokes) score is greater than or equal to 100. Multivariable logistic regression analyses were used to determine the independent association between SPAN-100 index status and 90-day outcomes. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of severe disability or death measured 90 days after stroke, and the secondary outcomes were death alone and a composite of no disability/modest disability. RESULTS Of 7093 patients, 743 (10.5%) were SPAN-100 positive, and 2731 (38.5%) received intravenous thrombolysis. Compared with SPAN-100–negative patients, SPAN-100–positive patients were more likely to experience a catastrophic outcome (adjusted odds ratio [AOR], 9.03 [95% CI, 6.68-12.21]) or death alone (AOR, 5.03 [95% CI, 4.06-6.23]) and less likely to experience a favorable outcome (AOR, 0.08 [95% CI, 0.06-0.13]). However, there was an interaction between SPAN-100 index status and thrombolysis treatment (P < .001) revealing a reduction in the likelihood of severe disability/death with thrombolytic treatment for SPAN-100–positive (AOR, 0.46 [95% CI, 0.29-0.71]) but not SPAN-100–negative patients (AOR, 0.96 [95% CI, 0.85-1.07]). Similar interactions between SPAN-100 index status and thrombolysis treatment were observed for the 2 secondary outcomes. CONCLUSION AND RELEVANCE Compared with the SPAN-100–negative patients with AIS, the SPAN-100–positive patients with AIS seem to have poorer 3-month outcomes but may derive greater benefit when treated with intravenous thrombolysis. The SPAN-100–positive patients are often excluded from AIS clinical trials but should probably not be denied thrombolysis treatment on the basis of such a profile alone.
JAMA Neurol. 2014;71(7):848-854. doi:10.1001/jamaneurol.2014.689 Published online May 5, 2014. 848
Author Affiliations: Department of Neurosciences, Medical University of South Carolina, Charleston (Ovbiagele); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (Reeves, Nasiri); Clinical and Translational Science Institute, University of California, San Francisco (Johnston); Stroke Trials Unit, University of Nottingham, Nottingham, England (Bath); Stroke Outcomes Research Unit, Division of Neurology, University of Toronto, Toronto, Ontario, Canada (Saposnik). Group Information: The VISTA-Acute Collaboration Steering Committee members are listed at the end of the article. Corresponding Author: Bruce Ovbiagele, MD, MSc, MAS, Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas St, CSB 301, MSC 606, Charleston, SC 29425 ([email protected]). jamaneurology.com
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a Nanyang Technological University User on 05/31/2015
The SPAN-100 Index
Original Investigation Research
T
o facilitate the consistent use of a prognostic index by providers caring for patients with acute ischemic stroke (AIS), a simple and practical index called the Stroke Prognostication using Age and NIH Stroke Scale, created by combining age in years plus an National Institutes of Health Stroke Scale (NIHSS) score of 100 or higher (and hereafter referred to as the SPAN-100 index), was developed to be applied especially to highrisk patients (ie, elderly patients with a moderate to severe stroke).1 When applied to a modest-sized sample of patients with AIS (n = 624), the SPAN-100 index was shown to be of value in estimating risk of intracerebral hemorrhage and clinical outcomes, at several follow-up time points, regardless of intravenous thrombolysis treatment. 1 However, the question of whether very elderly patients with very severe strokes (presumably with otherwise very poor outcomes) benefit from intravenous thrombolysis to a greater or lesser extent than other patients with AIS has not been specifically explored.2 In our study, we aimed to determine if the SPAN-100 index is indeed a useful practical prognostic variable/indicator for outcomes after AIS, and to assess if intravenous thrombolysis may decrease the risk of a disabling stroke or death among high-risk patients with an expected poor outcome.
Methods The SPAN-100 index was created by combining age in years and an NIHSS score of 100 or higher. The NIHSS is a 15-item neurological examination scale with scores ranging from 0 to 42, with higher scores indicating more severe stroke.3-5 Individuals whose combined age in years plus NIHSS score was greater than or equal to 100 were designated as SPAN-100–positive patients, whereas those whose combined age in years plus NIHSS score was less than 100 were designated as SPAN-100–negative patients. The rationale for the use of this index was that (1) age and stroke severity are the 2 most important prognostic factors for AIS,6-9 (2) patients 80 years of age or older with a high NIHSS score (eg, ≥20) generally have poorer prognoses,10-14 (3) a simple practical index is warranted given several factors that limit consistent use of currently available scores in routine practice,15-19 and (4) the index performed well in a derivation cohort.1 Ethical approval was not obtained because our study is an analysis of a repository containing de-identified participant data. We applied the SPAN-100 index to participants with AIS whose medical records were entered into the Virtual International Stroke Trials Archive (VISTA) database; VISTA-Acute (http://www.vistacollaboration.org) is a collaborative registry that includes data from completed acute stroke clinical trials and that provides access to anonymized data for exploratory analyses. Further details of VISTA are published elsewhere.20,21 For the purpose of this analysis, relevant data extracted from the VISTA database had to meet the following criteria: (1) a minimum data set of 100 patients; (2) a baseline assessment within 24 hours of stroke onset, including recording of neurologic deficit by use of the NIHSS; (3) confirmation of stroke diagnosis by cerebral imaging within 7 days; and (4) outcome assessed 3 months after stroke onset. The present analysis included a total of 7141 patients who participated in 4 neuroprojamaneurology.com
tectant clinical trials and who met the aforementioned inclusion criteria. The identity of the 4 trials is not provided by VISTA. Onset-to-treatment duration represents the elapsed time from stroke onset to receiving the studied intervention treatment (not intravenous thrombolysis). The modified Rankin Scale (mRS) was the primary outcome measure used in our study. The mRS is a practical clinician-reported measure of global disability, often used in largescale multicenter studies, that defines 7 clinically discrete patient disability categories. The scale runs from 0 to 6, ranging from no symptoms of disability to death, and has been proven to be valid and reliable.5,22 The primary outcome in this analysis was a catastrophic outcome (defined as an mRS score of 4-6 [ie, moderate to severe disability or death]) at 3 months, and the secondary 3-month outcomes were death alone or a favorable outcome (defined as an mRS score of 0-2 [ie, no disability or modest disability]). With regard to statistical analysis, among 7141 patients with AIS, we excluded patients with missing data on age (n = 1), NIHSS score (n = 48), and mortality status (n = 47), leaving 7093 participants. Furthermore, 325 of the remaining 7093 patients (4.6%) were missing mRS data collected at 90 days. We first generated descriptive statistics comparing the characteristics of VISTA patients according to their 90-day survival status and functional level (mRS) using contingency tables. Bivariate P values of association were generated using χ2 analysis for categorical variables and t tests for continuous variables. Primary exposure variables of interest were SPAN-100 index status (positive [≥100] or negative [
Original Investigation
A Simple Risk Index and Thrombolytic Treatment Response in Acute Ischemic Stroke Bruce Ovbiagele, MD, MSc, MAS; Mathew J. Reeves, BVSc, PhD; Mojdeh Nasiri, MD; S. Claiborne Johnston, MD, PhD; Philip M. Bath, MD, FRCPath, FRCP; Gustavo Saposnik, MD, MSc, FRCPC; for the VISTA-Acute Collaboration Steering Committee
IMPORTANCE The Stroke Prognostication using Age and the NIH Stroke Scale index, created by combining age in years plus a National Institutes of Health (NIH) Stroke Scale score of 100 or higher (and hereafter referred to as the SPAN-100 index), is a simple risk score for estimating clinical outcomes for patients with acute ischemic stroke (AIS). The association between this index and response to intravenous thrombolysis for AIS has not been properly evaluated.
Supplemental content at jamaneurology.com CME Quiz at jamanetworkcme.com and CME Questions page 932
OBJECTIVE To assess the relationship between SPAN-100 index status and outcome following treatment with intravenous thrombolysis for AIS. DESIGN, SETTING, AND PARTICIPANTS Using the Virtual International Stroke Trials Archive (VISTA) database, an international repository of clinical trials data, we assessed the SPAN-100 index among 7093 patients with AIS who participated in 4 clinical trials from 2000 to 2006. The SPAN-100 index is considered positive if the sum of the age and the NIH Stroke Scale (a 15-item neurological examination scale with scores ranging from 0 to 42, with higher scores indicating more severe strokes) score is greater than or equal to 100. Multivariable logistic regression analyses were used to determine the independent association between SPAN-100 index status and 90-day outcomes. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of severe disability or death measured 90 days after stroke, and the secondary outcomes were death alone and a composite of no disability/modest disability. RESULTS Of 7093 patients, 743 (10.5%) were SPAN-100 positive, and 2731 (38.5%) received intravenous thrombolysis. Compared with SPAN-100–negative patients, SPAN-100–positive patients were more likely to experience a catastrophic outcome (adjusted odds ratio [AOR], 9.03 [95% CI, 6.68-12.21]) or death alone (AOR, 5.03 [95% CI, 4.06-6.23]) and less likely to experience a favorable outcome (AOR, 0.08 [95% CI, 0.06-0.13]). However, there was an interaction between SPAN-100 index status and thrombolysis treatment (P < .001) revealing a reduction in the likelihood of severe disability/death with thrombolytic treatment for SPAN-100–positive (AOR, 0.46 [95% CI, 0.29-0.71]) but not SPAN-100–negative patients (AOR, 0.96 [95% CI, 0.85-1.07]). Similar interactions between SPAN-100 index status and thrombolysis treatment were observed for the 2 secondary outcomes. CONCLUSION AND RELEVANCE Compared with the SPAN-100–negative patients with AIS, the SPAN-100–positive patients with AIS seem to have poorer 3-month outcomes but may derive greater benefit when treated with intravenous thrombolysis. The SPAN-100–positive patients are often excluded from AIS clinical trials but should probably not be denied thrombolysis treatment on the basis of such a profile alone.
JAMA Neurol. 2014;71(7):848-854. doi:10.1001/jamaneurol.2014.689 Published online May 5, 2014. 848
Author Affiliations: Department of Neurosciences, Medical University of South Carolina, Charleston (Ovbiagele); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (Reeves, Nasiri); Clinical and Translational Science Institute, University of California, San Francisco (Johnston); Stroke Trials Unit, University of Nottingham, Nottingham, England (Bath); Stroke Outcomes Research Unit, Division of Neurology, University of Toronto, Toronto, Ontario, Canada (Saposnik). Group Information: The VISTA-Acute Collaboration Steering Committee members are listed at the end of the article. Corresponding Author: Bruce Ovbiagele, MD, MSc, MAS, Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucas St, CSB 301, MSC 606, Charleston, SC 29425 ([email protected]). jamaneurology.com
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a Nanyang Technological University User on 05/31/2015
The SPAN-100 Index
Original Investigation Research
T
o facilitate the consistent use of a prognostic index by providers caring for patients with acute ischemic stroke (AIS), a simple and practical index called the Stroke Prognostication using Age and NIH Stroke Scale, created by combining age in years plus an National Institutes of Health Stroke Scale (NIHSS) score of 100 or higher (and hereafter referred to as the SPAN-100 index), was developed to be applied especially to highrisk patients (ie, elderly patients with a moderate to severe stroke).1 When applied to a modest-sized sample of patients with AIS (n = 624), the SPAN-100 index was shown to be of value in estimating risk of intracerebral hemorrhage and clinical outcomes, at several follow-up time points, regardless of intravenous thrombolysis treatment. 1 However, the question of whether very elderly patients with very severe strokes (presumably with otherwise very poor outcomes) benefit from intravenous thrombolysis to a greater or lesser extent than other patients with AIS has not been specifically explored.2 In our study, we aimed to determine if the SPAN-100 index is indeed a useful practical prognostic variable/indicator for outcomes after AIS, and to assess if intravenous thrombolysis may decrease the risk of a disabling stroke or death among high-risk patients with an expected poor outcome.
Methods The SPAN-100 index was created by combining age in years and an NIHSS score of 100 or higher. The NIHSS is a 15-item neurological examination scale with scores ranging from 0 to 42, with higher scores indicating more severe stroke.3-5 Individuals whose combined age in years plus NIHSS score was greater than or equal to 100 were designated as SPAN-100–positive patients, whereas those whose combined age in years plus NIHSS score was less than 100 were designated as SPAN-100–negative patients. The rationale for the use of this index was that (1) age and stroke severity are the 2 most important prognostic factors for AIS,6-9 (2) patients 80 years of age or older with a high NIHSS score (eg, ≥20) generally have poorer prognoses,10-14 (3) a simple practical index is warranted given several factors that limit consistent use of currently available scores in routine practice,15-19 and (4) the index performed well in a derivation cohort.1 Ethical approval was not obtained because our study is an analysis of a repository containing de-identified participant data. We applied the SPAN-100 index to participants with AIS whose medical records were entered into the Virtual International Stroke Trials Archive (VISTA) database; VISTA-Acute (http://www.vistacollaboration.org) is a collaborative registry that includes data from completed acute stroke clinical trials and that provides access to anonymized data for exploratory analyses. Further details of VISTA are published elsewhere.20,21 For the purpose of this analysis, relevant data extracted from the VISTA database had to meet the following criteria: (1) a minimum data set of 100 patients; (2) a baseline assessment within 24 hours of stroke onset, including recording of neurologic deficit by use of the NIHSS; (3) confirmation of stroke diagnosis by cerebral imaging within 7 days; and (4) outcome assessed 3 months after stroke onset. The present analysis included a total of 7141 patients who participated in 4 neuroprojamaneurology.com
tectant clinical trials and who met the aforementioned inclusion criteria. The identity of the 4 trials is not provided by VISTA. Onset-to-treatment duration represents the elapsed time from stroke onset to receiving the studied intervention treatment (not intravenous thrombolysis). The modified Rankin Scale (mRS) was the primary outcome measure used in our study. The mRS is a practical clinician-reported measure of global disability, often used in largescale multicenter studies, that defines 7 clinically discrete patient disability categories. The scale runs from 0 to 6, ranging from no symptoms of disability to death, and has been proven to be valid and reliable.5,22 The primary outcome in this analysis was a catastrophic outcome (defined as an mRS score of 4-6 [ie, moderate to severe disability or death]) at 3 months, and the secondary 3-month outcomes were death alone or a favorable outcome (defined as an mRS score of 0-2 [ie, no disability or modest disability]). With regard to statistical analysis, among 7141 patients with AIS, we excluded patients with missing data on age (n = 1), NIHSS score (n = 48), and mortality status (n = 47), leaving 7093 participants. Furthermore, 325 of the remaining 7093 patients (4.6%) were missing mRS data collected at 90 days. We first generated descriptive statistics comparing the characteristics of VISTA patients according to their 90-day survival status and functional level (mRS) using contingency tables. Bivariate P values of association were generated using χ2 analysis for categorical variables and t tests for continuous variables. Primary exposure variables of interest were SPAN-100 index status (positive [≥100] or negative [
