Carotid Disease & Stroke

LOS ANGELES - Although patients with carotid artery stenosis randomized to the stenting arm of the CREST generally had better health status measures at 2 and 4 weeks following their intervention, by 1 year “all between-group differences had entirely resolved” when compared with the patients randomized to carotid endarterectomy, Dr. Joshua M. Stolker said at the International Stroke Conference.

The two treatment alternatives tested in the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) led to nearly identical long-term outcomes for quality-of-life despite an excess of strokes in the carotid stenting arm, and despite the finding in a new, exploratory analysis of health status outcomes that strokes produced a markedly larger decrement in health status than did myocardial infarctions or cranial nerve palsy. The worse outcomes with stroke probably did not affect the overall outcome of the stented patients because the number of strokes - and especially the number of major strokes - was relatively small in CREST, “so overall, there was no difference for the whole population despite the impact of stroke,” said Dr. Stolker, a cardiologist at Saint Louis University. In CREST, stented patients had a 1.8% higher rate of all strokes, compared with the endarterectomy patients, including a 0.5% excess rate of major strokes.

Stroke patients showed statistically significant impairments, compared with the patients without stroke, in seven of the eight health status outcome subscales measured using the Short Form (SF)-36: physical function, role physical, vitality, pain, social function, role emotional, and mental health. In contrast, after 1 year patients who had an MI following their surgery had a deficit only in the measure of general health, compared with the patients who did not have an MI. And patients who developed cranial-nerve palsy after their surgery had no 1-year deficits for any health-status measure, compared with the patients who did not develop cranial-nerve palsy.

These results “confirmed what a lot of us already suspected, that periprocedural stroke had a significant impact on 1-year health status across multiple SF-36 outcomes, but periprocedural MI and cranial-nerve palsy did not,” Dr. Stolker said.

The greatest impact on health status occurred in patients with major periprocedural strokes, who on average showed significant reductions in all eight subscales of the SF-36 at 1-year follow-up. Patients with minor periprocedural strokes had, on average, significant 1-year drops in “three or four” SF-36 subscales, compared with CREST patients who did not have strokes.

CREST randomized more than 2,500 patients. The study's primary end point results - the periprocedural rate of stroke, MI, or death plus the 4-year rate of ipsilateral stroke - showed no significant difference between the two study arms, according to results reported last year (N. Engl. J. Med. 2010;363:11-23). Dr. Stolker's new report focused on a prespecified analysis of health status outcomes.

In addition to the eight subscales of the SF-36, the researchers also measured changes in health status by six parameters measures by modified Likert scales: difficulty walking, difficulty eating and swallowing, difficulty driving, headaches, neck pain, and leg pain. The new analysis showed that at 2 weeks after the interventions, patients who had undergone carotid stenting had, on average, significantly better health-status scores for five of the eight SF-36 subscales. One year after the intervention, both the stented and open surgery arms showed, on average, nearly identical scores for all subscales.

The six additional parameters scored on a modified Likert scale showed a roughly similar pattern. After 2 weeks, the stented patients had significantly better scores for difficulty eating and swallowing, difficulty driving, headache, and neck pain, while the endarterectomy patients had a significant edge for difficulty walking and leg pain. These between-group differences began diminishing at 4 weeks and, at 1 year after the intervention, neither procedure had a significant difference for any of the six measures.

CREST was funded by the NIH, and  Abbott Vascular Solutions, the company that markets the stent and embolic protection device used in the study.

LOS ANGELES - Although patients with carotid artery stenosis randomized to the stenting arm of the CREST generally had better health status measures at 2 and 4 weeks following their intervention, by 1 year “all between-group differences had entirely resolved” when compared with the patients randomized to carotid endarterectomy, Dr. Joshua M. Stolker said at the International Stroke Conference.

The two treatment alternatives tested in the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) led to nearly identical long-term outcomes for quality-of-life despite an excess of strokes in the carotid stenting arm, and despite the finding in a new, exploratory analysis of health status outcomes that strokes produced a markedly larger decrement in health status than did myocardial infarctions or cranial nerve palsy. The worse outcomes with stroke probably did not affect the overall outcome of the stented patients because the number of strokes - and especially the number of major strokes - was relatively small in CREST, “so overall, there was no difference for the whole population despite the impact of stroke,” said Dr. Stolker, a cardiologist at Saint Louis University. In CREST, stented patients had a 1.8% higher rate of all strokes, compared with the endarterectomy patients, including a 0.5% excess rate of major strokes.

Stroke patients showed statistically significant impairments, compared with the patients without stroke, in seven of the eight health status outcome subscales measured using the Short Form (SF)-36: physical function, role physical, vitality, pain, social function, role emotional, and mental health. In contrast, after 1 year patients who had an MI following their surgery had a deficit only in the measure of general health, compared with the patients who did not have an MI. And patients who developed cranial-nerve palsy after their surgery had no 1-year deficits for any health-status measure, compared with the patients who did not develop cranial-nerve palsy.

These results “confirmed what a lot of us already suspected, that periprocedural stroke had a significant impact on 1-year health status across multiple SF-36 outcomes, but periprocedural MI and cranial-nerve palsy did not,” Dr. Stolker said.

The greatest impact on health status occurred in patients with major periprocedural strokes, who on average showed significant reductions in all eight subscales of the SF-36 at 1-year follow-up. Patients with minor periprocedural strokes had, on average, significant 1-year drops in “three or four” SF-36 subscales, compared with CREST patients who did not have strokes.

CREST randomized more than 2,500 patients. The study's primary end point results - the periprocedural rate of stroke, MI, or death plus the 4-year rate of ipsilateral stroke - showed no significant difference between the two study arms, according to results reported last year (N. Engl. J. Med. 2010;363:11-23). Dr. Stolker's new report focused on a prespecified analysis of health status outcomes.

In addition to the eight subscales of the SF-36, the researchers also measured changes in health status by six parameters measures by modified Likert scales: difficulty walking, difficulty eating and swallowing, difficulty driving, headaches, neck pain, and leg pain. The new analysis showed that at 2 weeks after the interventions, patients who had undergone carotid stenting had, on average, significantly better health-status scores for five of the eight SF-36 subscales. One year after the intervention, both the stented and open surgery arms showed, on average, nearly identical scores for all subscales.

The six additional parameters scored on a modified Likert scale showed a roughly similar pattern. After 2 weeks, the stented patients had significantly better scores for difficulty eating and swallowing, difficulty driving, headache, and neck pain, while the endarterectomy patients had a significant edge for difficulty walking and leg pain. These between-group differences began diminishing at 4 weeks and, at 1 year after the intervention, neither procedure had a significant difference for any of the six measures.

CREST was funded by the NIH, and  Abbott Vascular Solutions, the company that markets the stent and embolic protection device used in the study.

LOS ANGELES - Although patients with carotid artery stenosis randomized to the stenting arm of the CREST generally had better health status measures at 2 and 4 weeks following their intervention, by 1 year “all between-group differences had entirely resolved” when compared with the patients randomized to carotid endarterectomy, Dr. Joshua M. Stolker said at the International Stroke Conference.

The two treatment alternatives tested in the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) led to nearly identical long-term outcomes for quality-of-life despite an excess of strokes in the carotid stenting arm, and despite the finding in a new, exploratory analysis of health status outcomes that strokes produced a markedly larger decrement in health status than did myocardial infarctions or cranial nerve palsy. The worse outcomes with stroke probably did not affect the overall outcome of the stented patients because the number of strokes - and especially the number of major strokes - was relatively small in CREST, “so overall, there was no difference for the whole population despite the impact of stroke,” said Dr. Stolker, a cardiologist at Saint Louis University. In CREST, stented patients had a 1.8% higher rate of all strokes, compared with the endarterectomy patients, including a 0.5% excess rate of major strokes.

Stroke patients showed statistically significant impairments, compared with the patients without stroke, in seven of the eight health status outcome subscales measured using the Short Form (SF)-36: physical function, role physical, vitality, pain, social function, role emotional, and mental health. In contrast, after 1 year patients who had an MI following their surgery had a deficit only in the measure of general health, compared with the patients who did not have an MI. And patients who developed cranial-nerve palsy after their surgery had no 1-year deficits for any health-status measure, compared with the patients who did not develop cranial-nerve palsy.

These results “confirmed what a lot of us already suspected, that periprocedural stroke had a significant impact on 1-year health status across multiple SF-36 outcomes, but periprocedural MI and cranial-nerve palsy did not,” Dr. Stolker said.

The greatest impact on health status occurred in patients with major periprocedural strokes, who on average showed significant reductions in all eight subscales of the SF-36 at 1-year follow-up. Patients with minor periprocedural strokes had, on average, significant 1-year drops in “three or four” SF-36 subscales, compared with CREST patients who did not have strokes.

CREST randomized more than 2,500 patients. The study's primary end point results - the periprocedural rate of stroke, MI, or death plus the 4-year rate of ipsilateral stroke - showed no significant difference between the two study arms, according to results reported last year (N. Engl. J. Med. 2010;363:11-23). Dr. Stolker's new report focused on a prespecified analysis of health status outcomes.

In addition to the eight subscales of the SF-36, the researchers also measured changes in health status by six parameters measures by modified Likert scales: difficulty walking, difficulty eating and swallowing, difficulty driving, headaches, neck pain, and leg pain. The new analysis showed that at 2 weeks after the interventions, patients who had undergone carotid stenting had, on average, significantly better health-status scores for five of the eight SF-36 subscales. One year after the intervention, both the stented and open surgery arms showed, on average, nearly identical scores for all subscales.

The six additional parameters scored on a modified Likert scale showed a roughly similar pattern. After 2 weeks, the stented patients had significantly better scores for difficulty eating and swallowing, difficulty driving, headache, and neck pain, while the endarterectomy patients had a significant edge for difficulty walking and leg pain. These between-group differences began diminishing at 4 weeks and, at 1 year after the intervention, neither procedure had a significant difference for any of the six measures.

CREST was funded by the NIH, and  Abbott Vascular Solutions, the company that markets the stent and embolic protection device used in the study.

Earlier this year, the majority of a Food and Drug Administration advisory panel voted in favor of expanding the approved use of a carotid stent to include patients who are at standard surgical risk in addition to the previously approved indication for revascularization in patients at high surgical risk.

The FDA's Circulatory System Devices Panel voted 7-3 with 1 abstention that the benefits of the Acculink Carotid Stent, a self-expanding stent made of nickel and titanium manufactured by Abbott Vascular, outweigh the risks when used for the proposed population of patients, at standard surgical risk.

The indication under review is for the treatment of patients at standard risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: patients who have neurological symptoms and at least 70% stenosis of the common or internal carotid artery by ultrasound or at least 50% stenosis by angiogram; or patients without neurological symptoms and at least 70% stenosis of the internal carotid artery by ultrasound or at least 60% stenosis by angiogram. Patients must also have a reference vessel diameter within the range of 4.0 mm and 9.0 mm at the target lesion.

In 2004, the Acculink Carotid Stent was approved for use for carotid revascularization in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet slightly different criteria.

The company filed for approval of the expanded indication to include the lower surgical risk population based on the results of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), a randomized multicenter noninferiority study conducted in the United States and Canada comparing the outcomes of carotid artery stenting to the preferred method, carotid endarterectomy in patients who met the criteria in the proposed indication. At 1 year, the primary safety and effectiveness end point ? death, stroke, and myocardial infarction within 30 days of having the procedure plus the rate of ipsilateral stroke from 31 to 365 days after the procedure, was 7.1% among those who received the stent (1,131 patients) and 6.6% among those who underwent endarterectomy (1,176 patients), a difference that met the prespecified criteria for noninferiority.

Different components of the composite end point - periprocedural MIs and strokes -  were elevated among patients in the two arms: In the stent arm, the rate of strokes was 4.1%, compared with 1.9% in the surgical arm. MI at 30 days was 3.4% in the surgical arm, compared with 2% in the stent arm. Panelists varied on their opinions on the clinical significance of these differences.

The Acculink stent is approved in over 90 countries and more than 128,000 have been distributed worldwide, according to Abbott Vascular.

The CREST study was funded by Abbott Vascular, and was created by NIH and the New Jersey Medical School, Newark. The FDA usually follows the recommendations of its advisory panels.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict but not at this meeting.

Commenting on this story, Dr. Linda Harris, vice chair, faculty development, department of surgery, Millard Fillmore Gates Hospital-Kaleida, Buffalo, N.Y. , stated: "While FDA approval is important to allow use of the carotid stent for average risk patients, this does not guarantee that Medicare or other insurances will reimburse for patients at average risk. Further, it is important to closely dissect the CREST data, which clearly show a higher rate of stroke for stenting than for endarterectomy, with a higher MI rate for open surgery."

In addition, "the goal of the procedure is to prevent stroke, so a higher stroke rate is a significant issue. They also noted that in a quality of life evaluation, as part of the CREST study, stroke had significantly greater impact on patient wellness than did MI. There is clearly a role for carotid stenting; however, physicians must weigh the benefits and disadvantages of each treatment methodology for a given patient. The role for any interventional therapy for asymptomatic patients is currently also being reevaluated in the era of improved medical management, with statins, plavix, and b-blockers in addition to aspirin," Dr. Harris concluded.

Earlier this year, the majority of a Food and Drug Administration advisory panel voted in favor of expanding the approved use of a carotid stent to include patients who are at standard surgical risk in addition to the previously approved indication for revascularization in patients at high surgical risk.

The FDA's Circulatory System Devices Panel voted 7-3 with 1 abstention that the benefits of the Acculink Carotid Stent, a self-expanding stent made of nickel and titanium manufactured by Abbott Vascular, outweigh the risks when used for the proposed population of patients, at standard surgical risk.

The indication under review is for the treatment of patients at standard risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: patients who have neurological symptoms and at least 70% stenosis of the common or internal carotid artery by ultrasound or at least 50% stenosis by angiogram; or patients without neurological symptoms and at least 70% stenosis of the internal carotid artery by ultrasound or at least 60% stenosis by angiogram. Patients must also have a reference vessel diameter within the range of 4.0 mm and 9.0 mm at the target lesion.

In 2004, the Acculink Carotid Stent was approved for use for carotid revascularization in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet slightly different criteria.

The company filed for approval of the expanded indication to include the lower surgical risk population based on the results of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), a randomized multicenter noninferiority study conducted in the United States and Canada comparing the outcomes of carotid artery stenting to the preferred method, carotid endarterectomy in patients who met the criteria in the proposed indication. At 1 year, the primary safety and effectiveness end point ? death, stroke, and myocardial infarction within 30 days of having the procedure plus the rate of ipsilateral stroke from 31 to 365 days after the procedure, was 7.1% among those who received the stent (1,131 patients) and 6.6% among those who underwent endarterectomy (1,176 patients), a difference that met the prespecified criteria for noninferiority.

Different components of the composite end point - periprocedural MIs and strokes -  were elevated among patients in the two arms: In the stent arm, the rate of strokes was 4.1%, compared with 1.9% in the surgical arm. MI at 30 days was 3.4% in the surgical arm, compared with 2% in the stent arm. Panelists varied on their opinions on the clinical significance of these differences.

The Acculink stent is approved in over 90 countries and more than 128,000 have been distributed worldwide, according to Abbott Vascular.

The CREST study was funded by Abbott Vascular, and was created by NIH and the New Jersey Medical School, Newark. The FDA usually follows the recommendations of its advisory panels.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict but not at this meeting.

Commenting on this story, Dr. Linda Harris, vice chair, faculty development, department of surgery, Millard Fillmore Gates Hospital-Kaleida, Buffalo, N.Y. , stated: "While FDA approval is important to allow use of the carotid stent for average risk patients, this does not guarantee that Medicare or other insurances will reimburse for patients at average risk. Further, it is important to closely dissect the CREST data, which clearly show a higher rate of stroke for stenting than for endarterectomy, with a higher MI rate for open surgery."

In addition, "the goal of the procedure is to prevent stroke, so a higher stroke rate is a significant issue. They also noted that in a quality of life evaluation, as part of the CREST study, stroke had significantly greater impact on patient wellness than did MI. There is clearly a role for carotid stenting; however, physicians must weigh the benefits and disadvantages of each treatment methodology for a given patient. The role for any interventional therapy for asymptomatic patients is currently also being reevaluated in the era of improved medical management, with statins, plavix, and b-blockers in addition to aspirin," Dr. Harris concluded.

Earlier this year, the majority of a Food and Drug Administration advisory panel voted in favor of expanding the approved use of a carotid stent to include patients who are at standard surgical risk in addition to the previously approved indication for revascularization in patients at high surgical risk.

The FDA's Circulatory System Devices Panel voted 7-3 with 1 abstention that the benefits of the Acculink Carotid Stent, a self-expanding stent made of nickel and titanium manufactured by Abbott Vascular, outweigh the risks when used for the proposed population of patients, at standard surgical risk.

The indication under review is for the treatment of patients at standard risk for adverse events from carotid endarterectomy who require carotid revascularization and meet the following criteria: patients who have neurological symptoms and at least 70% stenosis of the common or internal carotid artery by ultrasound or at least 50% stenosis by angiogram; or patients without neurological symptoms and at least 70% stenosis of the internal carotid artery by ultrasound or at least 60% stenosis by angiogram. Patients must also have a reference vessel diameter within the range of 4.0 mm and 9.0 mm at the target lesion.

In 2004, the Acculink Carotid Stent was approved for use for carotid revascularization in patients at high risk for adverse events from carotid endarterectomy who require carotid revascularization and meet slightly different criteria.

The company filed for approval of the expanded indication to include the lower surgical risk population based on the results of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), a randomized multicenter noninferiority study conducted in the United States and Canada comparing the outcomes of carotid artery stenting to the preferred method, carotid endarterectomy in patients who met the criteria in the proposed indication. At 1 year, the primary safety and effectiveness end point ? death, stroke, and myocardial infarction within 30 days of having the procedure plus the rate of ipsilateral stroke from 31 to 365 days after the procedure, was 7.1% among those who received the stent (1,131 patients) and 6.6% among those who underwent endarterectomy (1,176 patients), a difference that met the prespecified criteria for noninferiority.

Different components of the composite end point - periprocedural MIs and strokes -  were elevated among patients in the two arms: In the stent arm, the rate of strokes was 4.1%, compared with 1.9% in the surgical arm. MI at 30 days was 3.4% in the surgical arm, compared with 2% in the stent arm. Panelists varied on their opinions on the clinical significance of these differences.

The Acculink stent is approved in over 90 countries and more than 128,000 have been distributed worldwide, according to Abbott Vascular.

The CREST study was funded by Abbott Vascular, and was created by NIH and the New Jersey Medical School, Newark. The FDA usually follows the recommendations of its advisory panels.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict but not at this meeting.

Commenting on this story, Dr. Linda Harris, vice chair, faculty development, department of surgery, Millard Fillmore Gates Hospital-Kaleida, Buffalo, N.Y. , stated: "While FDA approval is important to allow use of the carotid stent for average risk patients, this does not guarantee that Medicare or other insurances will reimburse for patients at average risk. Further, it is important to closely dissect the CREST data, which clearly show a higher rate of stroke for stenting than for endarterectomy, with a higher MI rate for open surgery."

In addition, "the goal of the procedure is to prevent stroke, so a higher stroke rate is a significant issue. They also noted that in a quality of life evaluation, as part of the CREST study, stroke had significantly greater impact on patient wellness than did MI. There is clearly a role for carotid stenting; however, physicians must weigh the benefits and disadvantages of each treatment methodology for a given patient. The role for any interventional therapy for asymptomatic patients is currently also being reevaluated in the era of improved medical management, with statins, plavix, and b-blockers in addition to aspirin," Dr. Harris concluded.