Leukoaraiosis Increases Risk for Periprocedural Stroke
Leukoaraiosis Increases Risk for Periprocedural Stroke
June 1, 2009 (Stockholm, Sweden) — A substudy of the International Carotid Stenosis Study (ICSS) shows that white-matter changes are associated with an increase in the risk for periprocedural stroke, myocardial infarction (MI), or death with carotid endarterectomy, but particularly with carotid stenting.
"We were able to show that white-matter changes increase the risk of stroke in both treatment groups," lead author Joerg Ederle, MD, from the Stroke Research Group at University College London Institute of Neurology, in the United Kingdom, told attendees here. While the risk was higher with stenting relative to endarterectomy for each quartile of white-matter score, he noted, the relative increase in risk was similar in both groups.
"In essence, the white-matter-changes study does not alter the overall conclusion of ICSS, that surgery remains the treatment of choice for symptomatic carotid stenosis," Dr. Ederle told Medscape Neurology & Neurosurgery. "Clinicians should be aware of the increased risk of perioperative stroke, death, or MI in patients with white-matter changes when advising their patients on treatment of symptomatic carotid stenosis."
The results were presented here at the XVIII European Stroke Conference, along with the main safety results of ICSS, reported separately by Medscape Neurology & Neurosurgery.
Uncertain Significance
White-matter changes, or leukoaraiosis, are visible on computed tomography (CT) scans as areas of low attenuation and on magnetic resonance imaging (MRI) as areas of high-signal intensity on T2-weighted and fluid-attenuated inversion-recovery (FLAIR) images, Dr. Ederle said. The precise etiology and clinical significance of white-matter changes are still uncertain, he said, but there is some suggestion from the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the landmark endarterectomy trial, that these changes may be associated with an increased risk for stroke. To date, no data are available for carotid stenting, he noted.
The ICSS trial is a randomized double-blind study comparing stenting with endarterectomy in patients with carotid stenosis of greater than 50% symptomatic within 6 months prior to randomization. A total of 1710 patients were included in the intention-to-treat analysis, 853 randomized to stenting and 857 to surgery.
The primary aim of the ICSS trial is to determine long-term survival free of disabling stroke. Sufficient follow-up for this end point is expected to be complete in 2011. At the meeting here, the ICSS investigators presented primary safety data on the 30-day rate of stroke, MI, or death, measured up to 120 days after randomization. Those results showed significantly higher rates of stroke, MI, and death with stenting vs endarterectomy.
"We therefore posed the question in ICSS if white-matter changes are associated with increased risk of stroke, MI, or death, which was the primary outcome measure of the 30-day analysis, up to 120 days after randomization, and if there is a difference in risk between stenting and surgery," Dr. Ederle said.
For this study, CT or MRI scans carried out prior to the procedure were available in 1084 of the 1710 patients; 559 of those randomized to stenting and 525 randomized to surgery. The extent of white-matter disease was rated in each using the Age-Related White-Matter Changes (ARWMC) score validated by Wahlund et al.
Each brain region is rated on a scale of 0 to 3, and the scores in all regions are added, giving a maximum of 30, he explained. All images were rated blind to treatment and outcome. Total scores in this study were distributed equally in the stenting and surgery groups, he noted. The median score in both groups was 6, and this was chosen as the cutoff to dichotomize white-matter scores for analysis.
Pooling both treatment groups together, they found that white-matter changes significantly increased the risk for stroke, MI, or death. Using the white-matter score as a continuous variable, they found a significant increase in risk for each 1-point increase in the white-matter score.
Table 1. Risk for Stroke, MI or Death Associated With Increasing White-Matter Score
When they plotted the Kaplan-Meier cumulative incidence for each quartile of the total white-matter score, the risk for stroke, MI, or death was higher for stenting than endarterectomy for each quartile, Dr. Ederle noted. "The difference in risk is particularly high for stenting in patients with a white-matter score greater than 10," he added.
When white-matter scores were dichotomized at 6, patients randomized to stenting with a white-matter score greater than 6 had a significantly higher incidence of stroke, MI, or death than those with a score lower than 6. The same analysis in the surgery group also showed an increase in risk with higher white-matter scores, but to a lesser extent than with stenting, he noted.
Table 2. Cumulative Incidence of Stroke, MI or Death for Higher vs Lower White-Matter Scores, by Intervention
In a comparison of the risk between stenting and surgery in patients with scores above and below 6, he noted, "stenting carried a higher risk of stroke, MI, or death in both groups, with a hazard ratio above 1.5" (HR 1.53 [95% CI, 0.72 – 3.27]; P = .68). The relative difference in risk favoring endarterectomy was similar in patients with low and high scores, he noted.
These findings should be interpreted in the context of the overall ICSS findings, Dr. Ederle said in an interview, namely an increased risk of perioperative stroke, death, or MI with stenting vs surgery. "Regardless of the extent of white-matter changes, stenting was always more hazardous, particularly so with increasing severity, and we were not able to identify a group of patients in whom stenting might be a safer option."
Because their analysis showed a similar increase in risk in both treatment groups with increasing white-matter changes, it is not possible to base treatment choice on the extent of white-matter changes, he added. "This finding would have been even more important had the overall result of ICSS shown no difference between stenting and carotid endarterectomy."
XVIII European Stroke Conference.
June 1, 2009 (Stockholm, Sweden) — A substudy of the International Carotid Stenosis Study (ICSS) shows that white-matter changes are associated with an increase in the risk for periprocedural stroke, myocardial infarction (MI), or death with carotid endarterectomy, but particularly with carotid stenting.
"We were able to show that white-matter changes increase the risk of stroke in both treatment groups," lead author Joerg Ederle, MD, from the Stroke Research Group at University College London Institute of Neurology, in the United Kingdom, told attendees here. While the risk was higher with stenting relative to endarterectomy for each quartile of white-matter score, he noted, the relative increase in risk was similar in both groups.
"In essence, the white-matter-changes study does not alter the overall conclusion of ICSS, that surgery remains the treatment of choice for symptomatic carotid stenosis," Dr. Ederle told Medscape Neurology & Neurosurgery. "Clinicians should be aware of the increased risk of perioperative stroke, death, or MI in patients with white-matter changes when advising their patients on treatment of symptomatic carotid stenosis."
The results were presented here at the XVIII European Stroke Conference, along with the main safety results of ICSS, reported separately by Medscape Neurology & Neurosurgery.
Uncertain Significance
White-matter changes, or leukoaraiosis, are visible on computed tomography (CT) scans as areas of low attenuation and on magnetic resonance imaging (MRI) as areas of high-signal intensity on T2-weighted and fluid-attenuated inversion-recovery (FLAIR) images, Dr. Ederle said. The precise etiology and clinical significance of white-matter changes are still uncertain, he said, but there is some suggestion from the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the landmark endarterectomy trial, that these changes may be associated with an increased risk for stroke. To date, no data are available for carotid stenting, he noted.
The ICSS trial is a randomized double-blind study comparing stenting with endarterectomy in patients with carotid stenosis of greater than 50% symptomatic within 6 months prior to randomization. A total of 1710 patients were included in the intention-to-treat analysis, 853 randomized to stenting and 857 to surgery.
The primary aim of the ICSS trial is to determine long-term survival free of disabling stroke. Sufficient follow-up for this end point is expected to be complete in 2011. At the meeting here, the ICSS investigators presented primary safety data on the 30-day rate of stroke, MI, or death, measured up to 120 days after randomization. Those results showed significantly higher rates of stroke, MI, and death with stenting vs endarterectomy.
"We therefore posed the question in ICSS if white-matter changes are associated with increased risk of stroke, MI, or death, which was the primary outcome measure of the 30-day analysis, up to 120 days after randomization, and if there is a difference in risk between stenting and surgery," Dr. Ederle said.
For this study, CT or MRI scans carried out prior to the procedure were available in 1084 of the 1710 patients; 559 of those randomized to stenting and 525 randomized to surgery. The extent of white-matter disease was rated in each using the Age-Related White-Matter Changes (ARWMC) score validated by Wahlund et al.
Each brain region is rated on a scale of 0 to 3, and the scores in all regions are added, giving a maximum of 30, he explained. All images were rated blind to treatment and outcome. Total scores in this study were distributed equally in the stenting and surgery groups, he noted. The median score in both groups was 6, and this was chosen as the cutoff to dichotomize white-matter scores for analysis.
Pooling both treatment groups together, they found that white-matter changes significantly increased the risk for stroke, MI, or death. Using the white-matter score as a continuous variable, they found a significant increase in risk for each 1-point increase in the white-matter score.
Table 1. Risk for Stroke, MI or Death Associated With Increasing White-Matter Score
| End Point | Hazard Ratio | 95% CI | P |
| 1-point increase in white-matter score | 1.08 | 1.03 – 1.14 | < .001 |
When they plotted the Kaplan-Meier cumulative incidence for each quartile of the total white-matter score, the risk for stroke, MI, or death was higher for stenting than endarterectomy for each quartile, Dr. Ederle noted. "The difference in risk is particularly high for stenting in patients with a white-matter score greater than 10," he added.
When white-matter scores were dichotomized at 6, patients randomized to stenting with a white-matter score greater than 6 had a significantly higher incidence of stroke, MI, or death than those with a score lower than 6. The same analysis in the surgery group also showed an increase in risk with higher white-matter scores, but to a lesser extent than with stenting, he noted.
Table 2. Cumulative Incidence of Stroke, MI or Death for Higher vs Lower White-Matter Scores, by Intervention
| Group | ARWMC Score > 6 (%) | ARWMC Score < 6 (%) | P |
| Carotid artery stenting | 12.8 | 5.5 | .003 |
| Carotid endarterectomy | 7.2 | 3.7 | .069 |
In a comparison of the risk between stenting and surgery in patients with scores above and below 6, he noted, "stenting carried a higher risk of stroke, MI, or death in both groups, with a hazard ratio above 1.5" (HR 1.53 [95% CI, 0.72 – 3.27]; P = .68). The relative difference in risk favoring endarterectomy was similar in patients with low and high scores, he noted.
These findings should be interpreted in the context of the overall ICSS findings, Dr. Ederle said in an interview, namely an increased risk of perioperative stroke, death, or MI with stenting vs surgery. "Regardless of the extent of white-matter changes, stenting was always more hazardous, particularly so with increasing severity, and we were not able to identify a group of patients in whom stenting might be a safer option."
Because their analysis showed a similar increase in risk in both treatment groups with increasing white-matter changes, it is not possible to base treatment choice on the extent of white-matter changes, he added. "This finding would have been even more important had the overall result of ICSS shown no difference between stenting and carotid endarterectomy."
XVIII European Stroke Conference.