Carotid Disease & Stroke

NASHVILLE, TENN. – U.S. stroke specialists now face the challenge of making endovascular embolectomy a routinely available option for selected patients with acute ischemic stroke, Dr. Pooja Khatri said in an interview at the International Stroke Conference.

During the conference, which was sponsored by the American Heart Association, new reports from three independent, randomized controlled trials, as well as data from a fourth study published in January, collectively established endovascular embolectomy as the new standard-of-care treatment for acute ischemic stroke patients with a proximal occlusion of a large, intracerebral artery. The stroke community, however, now faces the responsibility of figuring out how to make this a reality.

Among the hurdles they face are using CT imaging or other methods to identify in daily practice the specific patients who will get the biggest benefit from endovascular treatment and finding a consensus within each region on how to triage acute stroke patients to centers that can perform embolectomy, said Dr. Khatri, professor of neurology and director of acute stroke at the University of Cincinnati. In Cincinnati, Dr. Khatri and her colleagues are planning to soon hold a retreat with representatives from other area hospitals to try to work out the logistics.Dr. Khatri has received research support from Penumbra and Genentech.

[email protected]
On Twitter @mitchelzoler

NASHVILLE, TENN. – U.S. stroke specialists now face the challenge of making endovascular embolectomy a routinely available option for selected patients with acute ischemic stroke, Dr. Pooja Khatri said in an interview at the International Stroke Conference.

During the conference, which was sponsored by the American Heart Association, new reports from three independent, randomized controlled trials, as well as data from a fourth study published in January, collectively established endovascular embolectomy as the new standard-of-care treatment for acute ischemic stroke patients with a proximal occlusion of a large, intracerebral artery. The stroke community, however, now faces the responsibility of figuring out how to make this a reality.

Among the hurdles they face are using CT imaging or other methods to identify in daily practice the specific patients who will get the biggest benefit from endovascular treatment and finding a consensus within each region on how to triage acute stroke patients to centers that can perform embolectomy, said Dr. Khatri, professor of neurology and director of acute stroke at the University of Cincinnati. In Cincinnati, Dr. Khatri and her colleagues are planning to soon hold a retreat with representatives from other area hospitals to try to work out the logistics.Dr. Khatri has received research support from Penumbra and Genentech.

[email protected]
On Twitter @mitchelzoler

NASHVILLE, TENN. – U.S. stroke specialists now face the challenge of making endovascular embolectomy a routinely available option for selected patients with acute ischemic stroke, Dr. Pooja Khatri said in an interview at the International Stroke Conference.

During the conference, which was sponsored by the American Heart Association, new reports from three independent, randomized controlled trials, as well as data from a fourth study published in January, collectively established endovascular embolectomy as the new standard-of-care treatment for acute ischemic stroke patients with a proximal occlusion of a large, intracerebral artery. The stroke community, however, now faces the responsibility of figuring out how to make this a reality.

Among the hurdles they face are using CT imaging or other methods to identify in daily practice the specific patients who will get the biggest benefit from endovascular treatment and finding a consensus within each region on how to triage acute stroke patients to centers that can perform embolectomy, said Dr. Khatri, professor of neurology and director of acute stroke at the University of Cincinnati. In Cincinnati, Dr. Khatri and her colleagues are planning to soon hold a retreat with representatives from other area hospitals to try to work out the logistics.Dr. Khatri has received research support from Penumbra and Genentech.

[email protected]
On Twitter @mitchelzoler

Rapid reversal of international normalized ratio, along with systolic blood pressure reduction, in patients with oral anticoagulant–associated intracerebral hemorrhage can significantly reduce the rates of hematoma enlargement and in-hospital mortality, a retrospective cohort study has found.

In the German study of 1,176 patients with oral anticoagulant–associated intracerebral hemorrhage, patients whose INR was reduced below 1.3 with use of vitamin K agonists and whose systolic BP was reduced below 160 mm Hg within 4 hours of admission had a 72% reduction in the rates of hematoma enlargement and 40% reduction in in-hospital mortality, compared with patients who did not achieve those reductions in that time frame.

Researchers also showed that there were no significant increases in hemorrhagic complications, but fewer ischemic complications, among patients who resumed oral anticoagulation, according to the study published online Feb. 24 in JAMA.

“Consensus exists that elevated international normalized ratio (INR) levels should be reversed to minimize hematoma enlargement, yet mode, timing, and extent of INR reversal are unclear [and] valid data on safety and clinical benefit of [oral anticoagulant] resumption are missing and remain to be established,” wrote Dr. Joji B. Kuramatsu of the University of Erlangen-Nuremberg, Germany, and coauthors (JAMA 2015;313:824-836 [doi:10.1001/jama.2015.0846]).

The study was supported by the Johannes and Frieda Marohn Foundation. Authors declared a range of funding, grants, fees, and honoraria from the pharmaceutical industry.

Rapid reversal of international normalized ratio, along with systolic blood pressure reduction, in patients with oral anticoagulant–associated intracerebral hemorrhage can significantly reduce the rates of hematoma enlargement and in-hospital mortality, a retrospective cohort study has found.

In the German study of 1,176 patients with oral anticoagulant–associated intracerebral hemorrhage, patients whose INR was reduced below 1.3 with use of vitamin K agonists and whose systolic BP was reduced below 160 mm Hg within 4 hours of admission had a 72% reduction in the rates of hematoma enlargement and 40% reduction in in-hospital mortality, compared with patients who did not achieve those reductions in that time frame.

Researchers also showed that there were no significant increases in hemorrhagic complications, but fewer ischemic complications, among patients who resumed oral anticoagulation, according to the study published online Feb. 24 in JAMA.

“Consensus exists that elevated international normalized ratio (INR) levels should be reversed to minimize hematoma enlargement, yet mode, timing, and extent of INR reversal are unclear [and] valid data on safety and clinical benefit of [oral anticoagulant] resumption are missing and remain to be established,” wrote Dr. Joji B. Kuramatsu of the University of Erlangen-Nuremberg, Germany, and coauthors (JAMA 2015;313:824-836 [doi:10.1001/jama.2015.0846]).

The study was supported by the Johannes and Frieda Marohn Foundation. Authors declared a range of funding, grants, fees, and honoraria from the pharmaceutical industry.

Rapid reversal of international normalized ratio, along with systolic blood pressure reduction, in patients with oral anticoagulant–associated intracerebral hemorrhage can significantly reduce the rates of hematoma enlargement and in-hospital mortality, a retrospective cohort study has found.

In the German study of 1,176 patients with oral anticoagulant–associated intracerebral hemorrhage, patients whose INR was reduced below 1.3 with use of vitamin K agonists and whose systolic BP was reduced below 160 mm Hg within 4 hours of admission had a 72% reduction in the rates of hematoma enlargement and 40% reduction in in-hospital mortality, compared with patients who did not achieve those reductions in that time frame.

Researchers also showed that there were no significant increases in hemorrhagic complications, but fewer ischemic complications, among patients who resumed oral anticoagulation, according to the study published online Feb. 24 in JAMA.

“Consensus exists that elevated international normalized ratio (INR) levels should be reversed to minimize hematoma enlargement, yet mode, timing, and extent of INR reversal are unclear [and] valid data on safety and clinical benefit of [oral anticoagulant] resumption are missing and remain to be established,” wrote Dr. Joji B. Kuramatsu of the University of Erlangen-Nuremberg, Germany, and coauthors (JAMA 2015;313:824-836 [doi:10.1001/jama.2015.0846]).

The study was supported by the Johannes and Frieda Marohn Foundation. Authors declared a range of funding, grants, fees, and honoraria from the pharmaceutical industry.

Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.

Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.

The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.

The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.

Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.

Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.

Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).

In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.

Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.

The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.

Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.

Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.

The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.

The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.

Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.

Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.

Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).

In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.

Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.

The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.

Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.

Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.

The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.

The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.

Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.

Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.

Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).

In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.

Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.

The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.

POINT: Medical treatment ends need for CEA or CAS.

By Anne L. Abbott, M.D.

The medical profession and the wider community must be congratulated upon their sustained efforts over recent decades that have seen an 80% fall in the average annual risk of stroke associated with moderate and severe (50%-99%) asymptomatic carotid stenosis (ACS).^1-6 This has been achieved by better medical treatment which consists of encouraging healthy lifestyle habits and appropriate use of medication. This major impact results from the combined effect of addressing all vascular risk factors in individual patients and efforts to use the best medical treatment available at the time. Rates are now so low (around 0.5% per year for ipsilateral stroke) that procedures, such as carotid endarterectomy (CEA), are now more likely to harm than help patients.⁷

Even if procedures were always completely risk-free, improved medical treatment may mean we have now reached the point where carotid procedures for ACS are safe but essentially ineffective for reducing stroke risk. The latest measurements of stroke risk using medical treatment alone indicate that only about 2.5% of patients with 50%-99% ACS will have a an ipsilateral stroke due to the carotid lesion during their remaining lifetime if they are receiving pretty good quality, current medical treatment alone. This is because the average age of identifying patients with ACS in past studies was about 70 years and the average survival following diagnosis was 10 years.¹ Further, only about half the strokes occurring in the distribution of an internal carotid artery with >60% proximal stenosis are due to the carotid lesion.⁸

Guidelines recommendations for CEA for 50%-99% or 60%-99% ACS rely on marginal, 20- to 30-year-old differences in stroke rates between patients given medical treatment alone versus those given additional CEA in best practice settings.^9-11  Such recommendations are not relevant to current clinical practice largely because the medical treatment used in these studies is obsolete. Multiple independent observations regarding the improved stroke prevention efficacy of medical treatment,^1-6,12 and the additional observations below, provide ample evidence that current medical treatment alone is the only routine-practice (nontrial) approach we should use for  patients with 50%-99% ACS and any future role of carotid procedures in these patients could only apply to very small minority subgroups:

i. Current optimal medical treatment for patients with ACS has not been defined nor its impact measured. This means that it is likely we can lower the risk of stroke and other vascular complications in patients with ACS stenosis even further than has been achieved in the most recent studies. The definition of current optimal medical treatment will vary from patient to patient depending on which vascular risk factors they have and what has been shown effective in modifying these to reduce the risk of any complications of vascular disease.

ii. The 30-day peri-operative risk of stroke or death (and other significant complications) remains above 0% in the most recent results of trials and registries^13-15 and is usually not measured in routine practice. Latest measurements of average annual ipsilateral stroke risk with medical treatment alone are about 2-3 times lower than for patients who had CEA or CAS in the Asymp tomatic Carotid Atherosclerosis Study (ACAS)10 or the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).^{7, 13}

iii. Patients with 50%-99% ACS receiving current optimal medical treatment and with a sufficiently high average annual risk of ipsilateral stroke, indicating they may benefit from CEA, have not been identified. This rate would need to be in excess of at least 2.5%-3.0%, using results from ACAS,¹⁰ to expect any surgical benefit in routine practice. Studies of baseline degree of  ACS within the 50%-99% range,^10,11,16 plaque echolucency¹⁷ and most studies of detecting asymptomatic stenosis progression18-21 show that these parameters (used separately) confer a relative risk of stroke of only about 2.0-2.5. Therefore, a higher degree of baseline stenosis within the 50%-99% range, the detection of predominantly echolucent carotid plaques  or asymptomatic progression are too weak on their own to identity patients likely to benefit from an additional carotid procedure. Combinations of risk markers are required for sufficient risk discrimination. For instance, results from the Asymptomatic Carotid Stenosis and Risk of Stroke Study (largest study so far of medically managed patients with moderate or severe ACS) showed that a combination of clinical features, baseline degree of stenosis and standardized ultrasonic plaque characteristics can achieve average annual ipsilateral stroke risk stratification ranging  from <1.0% to 10%.¹⁶ However, like all stroke risk stratification studies performed so far, this study was performed before the era of current medical treatment and the results have not been independently tested.

iv. Even if patients with sufficiently higher than average annual risk of ipsilateral stroke are one day reliably identified, randomized trials of an additional carotid procedure will be required to determine if, and to what extent, that procedure is likely to reduce ipsilateral stroke risk in routine practice.

v. The available evidence from randomized trials and registries indicates that CAS causes about twice as many strokes or deaths as surgery (just like it does for symptomatic carotid stenosis). Therefore, currently CAS cannot be recommended.⁷  In conclusion, the available evidence clearly indicates that current medical treatment alone now offers the best chance of reducing the risk of ipsilateral stroke in patients with 50%-99% ACS. There is no current evidence of benefit from CEA or CAS in these patients overall, or in any particular subgroups. However, there is much evidence regarding procedural risk and unaffordable cost.  Risk of ipsilateral stroke is now so low without carotid procedures it is time to shift from the historic approach of identifying ACS primarily to administer CEA. Rather, it is time to properly recognize that carotid stenosis is a risk factor of all complications of vascular disease, more than it is for ipsilateral stroke.²²

The priority is to define current optimal medical treatment as best we can, recognising that patients with ACS are a risk-heterogenous population. Then we need quality independent measurements of its impact on risk of all vascular disease complications using quality prospective cohort studies. Risk stratification models should be used to identify those who may benefit from trials of more intensive medical treatment, motivational strategies, plus/minus the safest carotid procedures. If identifying patients with ACS for CEA in routine practice is to be feasible, this needs to be done within well organized environments that support patients with a wide range of stenosis severity with the primary aim of implementing current optimal medical treatment to prevent all vascular complications. Finally, it must be accepted that as medical treatment and its implementation continue to improve, the added value of carotid procedures, including for symptomatic carotid stenosis, will continue to recede until we can say, ‘good job - it is finally fixed and it is time to move on to other major health issues.’

Dr. Abbott is a neurologist and an associate professor at Monash University, Melbourne, Australia.

References

1. Stroke. 2009;40:e573-583
2. Eur J Vasc Endovasc Surg. 2009;37:625-632
3. Nat Rev Cardiol. 2011;9:116-124
4. Stroke. 2013;44
5. Management of asymptomatic carotid stenosis: Technology assessment report. 2012:83
6. Annals of Internal Medicine. 2013;158:676-685
7. Stroke. 2013;44:1186-1190
8. N Engl J Med. 2000;342:1693-1700
9. N Engl J Med. 1993;328:221-227.
10.JAMA. 1995;273:1421-1428
11. Lancet. 2004;363:1491-1502
12. Arch Neurol. 2010;67:180-186
13. N Engl J Med. 2010;363:11-23
14. J Vasc Surg. 2009;49:71-79
15. J Vasc Surg. 2011;53:307-315
16. J Vasc Surg. 2010;52:1486-1496 e1481-1485
17. Gupta A, Kesavabhotla K, Barbadaran H, Kamel H, Panda A, Giambrone A, et al. Plaque echolucency and stroke risk in asymptoamtioc carotid stenosis: A systematic review and meta-analysis. Stroke. 2014 in press.
18. J Vasc Surg. 1999;29:208-214; discussion 214-206
19. J Vasc Surg. 2013;58:128-135 e121
20  Stroke. 2013;44:792-794
21. J Vasc Surg. 2014;59:956-967
22. N Engl J Med. 1986;315:860-865.

COUNTERPOINT: Medical therapy alone is not always enough.

By Mark F. Conrad, M.D., M.MSc., and Richard P. Cambria M.D.

Stroke remains the 3rd leading cause of death in the United States.¹  It is estimated that 10% to 20% of ischemic strokes can be attributed to an ipsilateral, typically high-grade carotid stenosis, thus, asymptomatic carotid bifurcation stenosis remains a potentially significant public health problem.²  Epidemiologic studies indicate that 5% to 6% of the population >65 years of age will harbor an asymptomatic and potentially surgically significant carotid stenosis.¹  The modern literature linking the degree of stenosis of the internal carotid artery and risk of ipsilateral stroke dates to the natural history studies of Chambers and Norris published in the New England Journal of Medicine in 1986.³  These investigators demonstrated a significant correlation of stroke risk with a >70% ipsilateral carotid artery stenosis and progression under observation. 

Carotid endarterectomy (CEA) has been the standard of care for the prevention of stroke in patients with severe (>70%) asymptomatic carotid artery stenosis (ACS) for five decades.  This is supported by level 1 evidence from multiple randomized trials^{4, 5} and consensus guideline recommendations.^{2, 6}  Yet the use of CEA in patients with ACS has been recently challenged by a widely publicized review article⁷ whose author has embarked upon an anti-CEA crusade with the zealous fervor of one who worships at the altar of the statin.  In this review, 11 prospective studies of medical therapy of patients with ACS (defined by the author as >50% stenosis) were stratified by date of publication such that the four series published from 2000-2007 had a lower raw data stroke rate with medical management (.6- 1.3%) than the 1.5% stroke rate reported after CEA in the ACAS study.^4,7  The authors concluded that medical management alone is “at least 3-8” times more cost effective than CEA despite a complete lack of cost data in the cited articles.   In an effort to debunk this revisionist history, we will begin by addressing the four aforementioned trials and finish with a discussion of the recent literature including an observational study from our own institution.

The first study of the four followed the asymptomatic contralateral carotid artery of all patients enrolled in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) for 5 years to determine the risk of stroke in medically managed patients.⁸  There were 2,377 patients of whom 216 (9%) had a stenosis >60% but only 113 (4.7%) had a stenosis of 75-99%.  The 5-year risk of ipsilateral stroke in the 75-99% asymptomatic stenosis cohort was 18.5% or 3.7% per year (this did not include other neurologic events such as TIA or amaurosis fugax).⁸  However, in the meta-analysis, no stroke rate was included in the raw data column (which was the basis of the final calculated overall stroke risk) and the final estimate quoted used the 60%-99% cohort such that the annual stroke rate was reported as 3.2%.⁷

The Asymptomatic Carotid Stenosis and Risk of Ipsilateral Hemispheric Ischemic Events Study (ACSRS) was a multicenter study that followed 1,115 patients with ACS >50% by duplex scanning for 6-84 months (mean 37.1) with the goal of stratifying patients into cohorts of high and low risk for future neurologic events.⁹  They concluded that the annual stroke rate in high-risk patients was 4.3% versus 0.7% in low-risk patients.  There were 453 patients with 70%-99% stenosis by NASCET criteria with a raw stroke rate of 5.7% (1.9%/ year over an average 3-year follow-up) and a 5-year ipsilateral event rate of about 18%.⁹  However, when the patients with 50-69% were added, the raw stroke rate decreased to 1.3%.⁷

The Asymptomatic Stenosis Embolus Detection (ASED) study was a prospective trial that tested the theory that transcranial Doppler embolic signal detection would identify increased risk of ipsilateral neurologic events in patients with >60% ACS.¹⁰  Of the 240 arteries studied, 115 (48%) had a stenosis of 70%-99% but 10 of these patients were censored because they underwent CEA during the follow-up period.  Their outcomes were not further stratified by degree of stenosis but the average ipsilateral carotid event rate was 3.1% per year with a 1% stroke risk per year.^{7, 10}

The final, and most damning study in the meta-analysis, included a cohort of patients from the Second Manifestations of Arterial disease (SMART) study which is a registry of patients from the Netherlands with risk factors for, or symptoms of, arterial disease.

 This study attempted to determine the risk of new vascular event in patients with ACS but 996 (27% of the registry) patients with a history of cerebrovascular disease (undefined) were excluded from analysis.¹¹  They identified 221 patients (8% of 2684 eligible patients) with ACS >50% and reported an ipsilateral stroke event rate of .6%/year.⁷ 

However, in the 147 patients with a 70-99% stenosis, the hazard ratio for ischemic stroke was 1.7 but it was not possible to separate the patients with a moderate (50-69%) stenosis from the outcomes of those with more severe (>70%) disease.¹¹ 

The major flaw with this study is that the authors excluded the 996 patients with a history of cerebrovascular disease who were at highest risk of having an ACS and subsequently suffering a stroke.

The flaw with combining the results of the above studies to conclude that medical therapy is the best way to prevent stroke in patients with severe ACS is that only half (828/1,754, 47%) of the patients included had a severe (70-99%) stenosis that would warrant CEA in the United States.^{6, 7}

The majority of the patients studied would have been treated with best medical therapy and serial Duplex scanning. Indeed, when the moderate patients were excluded, the yearly stroke rates for patients with actual severe stenosis ranged from 2.0%-3.7%; substantially higher than the 1.5% stroke rate associated with CEA.^{8, 9}

Randomized prospective trials such as the asymptomatic carotid artery stenosis (ACAS) study published in 1995 and the more recently updated asymptomatic carotid surgery trial (ACST) indicated a quite similar annual stroke risk in the 2% range for patients treated with medical therapy as opposed to those randomized to carotid endarterectomy (this study was excluded from the meta-analysis because patients with a remote (>6 months before entry) history of neurologic events were included).^4,12 In addition, the 10-year follow-up data in the ACST trial demonstrated a sustained benefit for endarterectomy over optimal medical therapy.⁵ It is important to emphasize that in this trial some 80% of patients were on optimal medical therapy (aspirin plus statin agents) in the later years of the trial.

These long-term data indicate that while the protective effect of endarterectomy was more pronounced in those not on appropriate lipid-lowering therapy (the 10-year advantage of endarterectomy over medical therapy in the prevention of stroke was 5.8% in patients taking a statin and 6.2% in those who were not)  the protective effect of endarterectomy over optimal medical therapy was statistically significant (P=0.002).⁵

This is of course relevant because clinicians in the modern era have typically used data from ACST to counsel patients about the stroke risk of asymptomatic high-grade carotid stenosis.

Finally, we followed at a cohort of 115 patients with severe (>70%) ACS who did not undergo CEA for a variety of reasons.

The average follow-up was 27 months and 86% of patients were on statin therapy. 

The 5-year ipsilateral ischemic event rate was 30%, and 48% of these were strokes.  When stratified by degree of stenosis, the patients with a 90%-99% stenosis had an ipsilateral neurologic event rate of 55%. This is a single center experience but the stroke rate of 3% per year is consistent with contemporary series and reiterates the reality of this risk for medically treated patients.

The question remains. When the efficacy of a CEA for the prevention of stroke in patients with ACS is supported by level 1 evidence from multiple prospective, randomized trials, why would anyone who treats patients with carotid disease allow a meta-analysis of natural history studies (that redefines a severe stenosis as >50%) convince them otherwise?

We believe that the answer lies in the unsubstantiated conclusion that “current medical intervention was estimated at least 3 to 8 times more cost effective” than CEA.⁷ 

As health care in the United States continues to evolve, we are faced with the issue of how best to spend limited resource dollars.

Is it practical or cost efficient to perform preventative surgery?

In England, an annual stroke rate of 2%-3% in a small subset of the population may be acceptable but we are not ready to concede that in the United States.  
For now, we will follow the SVS practice guidelines for the management of ACS as they are evidenced based and definitive.

CEA in conjunction with medical therapy remains the best way to prevent stroke in patients with severe  (>70%) ACS.

Dr. Conrad is  an assistant professor of surgery, Harvard Medical School, Boston. Dr. Cambria is The Robert R. Linton MD Professor of Vascular and Endovascular Surgery, Harvard Medical School, Boston.

References

1.Neurology. 2006;67:1390-1395
2.Circulation. 2012;125:188-197
3.N Engl J of Med. 1986;315:860-865
4.JAMA. 1995;273:1421-1428
5.Lancet. 2010;376:1074-1084
6.Journal of Vascular Surgery. 2011;54:e1-31
7.Stroke. 2009;40:e573-583
8.N Engl J Med. 2000;342:1693-1700
9. Eur J Vasc Endovasc Surg. 2005;30:275-284
10.Stroke. 2005;36:1128-1133
11. Stroke. 2007;38:1470-1475
12. Lancet. 2004;363:1491-1502

POINT: Medical treatment ends need for CEA or CAS.

By Anne L. Abbott, M.D.

The medical profession and the wider community must be congratulated upon their sustained efforts over recent decades that have seen an 80% fall in the average annual risk of stroke associated with moderate and severe (50%-99%) asymptomatic carotid stenosis (ACS).^1-6 This has been achieved by better medical treatment which consists of encouraging healthy lifestyle habits and appropriate use of medication. This major impact results from the combined effect of addressing all vascular risk factors in individual patients and efforts to use the best medical treatment available at the time. Rates are now so low (around 0.5% per year for ipsilateral stroke) that procedures, such as carotid endarterectomy (CEA), are now more likely to harm than help patients.⁷

Even if procedures were always completely risk-free, improved medical treatment may mean we have now reached the point where carotid procedures for ACS are safe but essentially ineffective for reducing stroke risk. The latest measurements of stroke risk using medical treatment alone indicate that only about 2.5% of patients with 50%-99% ACS will have a an ipsilateral stroke due to the carotid lesion during their remaining lifetime if they are receiving pretty good quality, current medical treatment alone. This is because the average age of identifying patients with ACS in past studies was about 70 years and the average survival following diagnosis was 10 years.¹ Further, only about half the strokes occurring in the distribution of an internal carotid artery with >60% proximal stenosis are due to the carotid lesion.⁸

Guidelines recommendations for CEA for 50%-99% or 60%-99% ACS rely on marginal, 20- to 30-year-old differences in stroke rates between patients given medical treatment alone versus those given additional CEA in best practice settings.^9-11  Such recommendations are not relevant to current clinical practice largely because the medical treatment used in these studies is obsolete. Multiple independent observations regarding the improved stroke prevention efficacy of medical treatment,^1-6,12 and the additional observations below, provide ample evidence that current medical treatment alone is the only routine-practice (nontrial) approach we should use for  patients with 50%-99% ACS and any future role of carotid procedures in these patients could only apply to very small minority subgroups:

i. Current optimal medical treatment for patients with ACS has not been defined nor its impact measured. This means that it is likely we can lower the risk of stroke and other vascular complications in patients with ACS stenosis even further than has been achieved in the most recent studies. The definition of current optimal medical treatment will vary from patient to patient depending on which vascular risk factors they have and what has been shown effective in modifying these to reduce the risk of any complications of vascular disease.

ii. The 30-day peri-operative risk of stroke or death (and other significant complications) remains above 0% in the most recent results of trials and registries^13-15 and is usually not measured in routine practice. Latest measurements of average annual ipsilateral stroke risk with medical treatment alone are about 2-3 times lower than for patients who had CEA or CAS in the Asymp tomatic Carotid Atherosclerosis Study (ACAS)10 or the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).^{7, 13}

iii. Patients with 50%-99% ACS receiving current optimal medical treatment and with a sufficiently high average annual risk of ipsilateral stroke, indicating they may benefit from CEA, have not been identified. This rate would need to be in excess of at least 2.5%-3.0%, using results from ACAS,¹⁰ to expect any surgical benefit in routine practice. Studies of baseline degree of  ACS within the 50%-99% range,^10,11,16 plaque echolucency¹⁷ and most studies of detecting asymptomatic stenosis progression18-21 show that these parameters (used separately) confer a relative risk of stroke of only about 2.0-2.5. Therefore, a higher degree of baseline stenosis within the 50%-99% range, the detection of predominantly echolucent carotid plaques  or asymptomatic progression are too weak on their own to identity patients likely to benefit from an additional carotid procedure. Combinations of risk markers are required for sufficient risk discrimination. For instance, results from the Asymptomatic Carotid Stenosis and Risk of Stroke Study (largest study so far of medically managed patients with moderate or severe ACS) showed that a combination of clinical features, baseline degree of stenosis and standardized ultrasonic plaque characteristics can achieve average annual ipsilateral stroke risk stratification ranging  from <1.0% to 10%.¹⁶ However, like all stroke risk stratification studies performed so far, this study was performed before the era of current medical treatment and the results have not been independently tested.

iv. Even if patients with sufficiently higher than average annual risk of ipsilateral stroke are one day reliably identified, randomized trials of an additional carotid procedure will be required to determine if, and to what extent, that procedure is likely to reduce ipsilateral stroke risk in routine practice.

v. The available evidence from randomized trials and registries indicates that CAS causes about twice as many strokes or deaths as surgery (just like it does for symptomatic carotid stenosis). Therefore, currently CAS cannot be recommended.⁷  In conclusion, the available evidence clearly indicates that current medical treatment alone now offers the best chance of reducing the risk of ipsilateral stroke in patients with 50%-99% ACS. There is no current evidence of benefit from CEA or CAS in these patients overall, or in any particular subgroups. However, there is much evidence regarding procedural risk and unaffordable cost.  Risk of ipsilateral stroke is now so low without carotid procedures it is time to shift from the historic approach of identifying ACS primarily to administer CEA. Rather, it is time to properly recognize that carotid stenosis is a risk factor of all complications of vascular disease, more than it is for ipsilateral stroke.²²

The priority is to define current optimal medical treatment as best we can, recognising that patients with ACS are a risk-heterogenous population. Then we need quality independent measurements of its impact on risk of all vascular disease complications using quality prospective cohort studies. Risk stratification models should be used to identify those who may benefit from trials of more intensive medical treatment, motivational strategies, plus/minus the safest carotid procedures. If identifying patients with ACS for CEA in routine practice is to be feasible, this needs to be done within well organized environments that support patients with a wide range of stenosis severity with the primary aim of implementing current optimal medical treatment to prevent all vascular complications. Finally, it must be accepted that as medical treatment and its implementation continue to improve, the added value of carotid procedures, including for symptomatic carotid stenosis, will continue to recede until we can say, ‘good job - it is finally fixed and it is time to move on to other major health issues.’

Dr. Abbott is a neurologist and an associate professor at Monash University, Melbourne, Australia.

References

1. Stroke. 2009;40:e573-583
2. Eur J Vasc Endovasc Surg. 2009;37:625-632
3. Nat Rev Cardiol. 2011;9:116-124
4. Stroke. 2013;44
5. Management of asymptomatic carotid stenosis: Technology assessment report. 2012:83
6. Annals of Internal Medicine. 2013;158:676-685
7. Stroke. 2013;44:1186-1190
8. N Engl J Med. 2000;342:1693-1700
9. N Engl J Med. 1993;328:221-227.
10.JAMA. 1995;273:1421-1428
11. Lancet. 2004;363:1491-1502
12. Arch Neurol. 2010;67:180-186
13. N Engl J Med. 2010;363:11-23
14. J Vasc Surg. 2009;49:71-79
15. J Vasc Surg. 2011;53:307-315
16. J Vasc Surg. 2010;52:1486-1496 e1481-1485
17. Gupta A, Kesavabhotla K, Barbadaran H, Kamel H, Panda A, Giambrone A, et al. Plaque echolucency and stroke risk in asymptoamtioc carotid stenosis: A systematic review and meta-analysis. Stroke. 2014 in press.
18. J Vasc Surg. 1999;29:208-214; discussion 214-206
19. J Vasc Surg. 2013;58:128-135 e121
20  Stroke. 2013;44:792-794
21. J Vasc Surg. 2014;59:956-967
22. N Engl J Med. 1986;315:860-865.

COUNTERPOINT: Medical therapy alone is not always enough.

By Mark F. Conrad, M.D., M.MSc., and Richard P. Cambria M.D.

Stroke remains the 3rd leading cause of death in the United States.¹  It is estimated that 10% to 20% of ischemic strokes can be attributed to an ipsilateral, typically high-grade carotid stenosis, thus, asymptomatic carotid bifurcation stenosis remains a potentially significant public health problem.²  Epidemiologic studies indicate that 5% to 6% of the population >65 years of age will harbor an asymptomatic and potentially surgically significant carotid stenosis.¹  The modern literature linking the degree of stenosis of the internal carotid artery and risk of ipsilateral stroke dates to the natural history studies of Chambers and Norris published in the New England Journal of Medicine in 1986.³  These investigators demonstrated a significant correlation of stroke risk with a >70% ipsilateral carotid artery stenosis and progression under observation. 

Carotid endarterectomy (CEA) has been the standard of care for the prevention of stroke in patients with severe (>70%) asymptomatic carotid artery stenosis (ACS) for five decades.  This is supported by level 1 evidence from multiple randomized trials^{4, 5} and consensus guideline recommendations.^{2, 6}  Yet the use of CEA in patients with ACS has been recently challenged by a widely publicized review article⁷ whose author has embarked upon an anti-CEA crusade with the zealous fervor of one who worships at the altar of the statin.  In this review, 11 prospective studies of medical therapy of patients with ACS (defined by the author as >50% stenosis) were stratified by date of publication such that the four series published from 2000-2007 had a lower raw data stroke rate with medical management (.6- 1.3%) than the 1.5% stroke rate reported after CEA in the ACAS study.^4,7  The authors concluded that medical management alone is “at least 3-8” times more cost effective than CEA despite a complete lack of cost data in the cited articles.   In an effort to debunk this revisionist history, we will begin by addressing the four aforementioned trials and finish with a discussion of the recent literature including an observational study from our own institution.

The first study of the four followed the asymptomatic contralateral carotid artery of all patients enrolled in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) for 5 years to determine the risk of stroke in medically managed patients.⁸  There were 2,377 patients of whom 216 (9%) had a stenosis >60% but only 113 (4.7%) had a stenosis of 75-99%.  The 5-year risk of ipsilateral stroke in the 75-99% asymptomatic stenosis cohort was 18.5% or 3.7% per year (this did not include other neurologic events such as TIA or amaurosis fugax).⁸  However, in the meta-analysis, no stroke rate was included in the raw data column (which was the basis of the final calculated overall stroke risk) and the final estimate quoted used the 60%-99% cohort such that the annual stroke rate was reported as 3.2%.⁷

The Asymptomatic Carotid Stenosis and Risk of Ipsilateral Hemispheric Ischemic Events Study (ACSRS) was a multicenter study that followed 1,115 patients with ACS >50% by duplex scanning for 6-84 months (mean 37.1) with the goal of stratifying patients into cohorts of high and low risk for future neurologic events.⁹  They concluded that the annual stroke rate in high-risk patients was 4.3% versus 0.7% in low-risk patients.  There were 453 patients with 70%-99% stenosis by NASCET criteria with a raw stroke rate of 5.7% (1.9%/ year over an average 3-year follow-up) and a 5-year ipsilateral event rate of about 18%.⁹  However, when the patients with 50-69% were added, the raw stroke rate decreased to 1.3%.⁷

The Asymptomatic Stenosis Embolus Detection (ASED) study was a prospective trial that tested the theory that transcranial Doppler embolic signal detection would identify increased risk of ipsilateral neurologic events in patients with >60% ACS.¹⁰  Of the 240 arteries studied, 115 (48%) had a stenosis of 70%-99% but 10 of these patients were censored because they underwent CEA during the follow-up period.  Their outcomes were not further stratified by degree of stenosis but the average ipsilateral carotid event rate was 3.1% per year with a 1% stroke risk per year.^{7, 10}

The final, and most damning study in the meta-analysis, included a cohort of patients from the Second Manifestations of Arterial disease (SMART) study which is a registry of patients from the Netherlands with risk factors for, or symptoms of, arterial disease.

 This study attempted to determine the risk of new vascular event in patients with ACS but 996 (27% of the registry) patients with a history of cerebrovascular disease (undefined) were excluded from analysis.¹¹  They identified 221 patients (8% of 2684 eligible patients) with ACS >50% and reported an ipsilateral stroke event rate of .6%/year.⁷ 

However, in the 147 patients with a 70-99% stenosis, the hazard ratio for ischemic stroke was 1.7 but it was not possible to separate the patients with a moderate (50-69%) stenosis from the outcomes of those with more severe (>70%) disease.¹¹ 

The major flaw with this study is that the authors excluded the 996 patients with a history of cerebrovascular disease who were at highest risk of having an ACS and subsequently suffering a stroke.

The flaw with combining the results of the above studies to conclude that medical therapy is the best way to prevent stroke in patients with severe ACS is that only half (828/1,754, 47%) of the patients included had a severe (70-99%) stenosis that would warrant CEA in the United States.^{6, 7}

The majority of the patients studied would have been treated with best medical therapy and serial Duplex scanning. Indeed, when the moderate patients were excluded, the yearly stroke rates for patients with actual severe stenosis ranged from 2.0%-3.7%; substantially higher than the 1.5% stroke rate associated with CEA.^{8, 9}

Randomized prospective trials such as the asymptomatic carotid artery stenosis (ACAS) study published in 1995 and the more recently updated asymptomatic carotid surgery trial (ACST) indicated a quite similar annual stroke risk in the 2% range for patients treated with medical therapy as opposed to those randomized to carotid endarterectomy (this study was excluded from the meta-analysis because patients with a remote (>6 months before entry) history of neurologic events were included).^4,12 In addition, the 10-year follow-up data in the ACST trial demonstrated a sustained benefit for endarterectomy over optimal medical therapy.⁵ It is important to emphasize that in this trial some 80% of patients were on optimal medical therapy (aspirin plus statin agents) in the later years of the trial.

These long-term data indicate that while the protective effect of endarterectomy was more pronounced in those not on appropriate lipid-lowering therapy (the 10-year advantage of endarterectomy over medical therapy in the prevention of stroke was 5.8% in patients taking a statin and 6.2% in those who were not)  the protective effect of endarterectomy over optimal medical therapy was statistically significant (P=0.002).⁵

This is of course relevant because clinicians in the modern era have typically used data from ACST to counsel patients about the stroke risk of asymptomatic high-grade carotid stenosis.

Finally, we followed at a cohort of 115 patients with severe (>70%) ACS who did not undergo CEA for a variety of reasons.

The average follow-up was 27 months and 86% of patients were on statin therapy. 

The 5-year ipsilateral ischemic event rate was 30%, and 48% of these were strokes.  When stratified by degree of stenosis, the patients with a 90%-99% stenosis had an ipsilateral neurologic event rate of 55%. This is a single center experience but the stroke rate of 3% per year is consistent with contemporary series and reiterates the reality of this risk for medically treated patients.

The question remains. When the efficacy of a CEA for the prevention of stroke in patients with ACS is supported by level 1 evidence from multiple prospective, randomized trials, why would anyone who treats patients with carotid disease allow a meta-analysis of natural history studies (that redefines a severe stenosis as >50%) convince them otherwise?

We believe that the answer lies in the unsubstantiated conclusion that “current medical intervention was estimated at least 3 to 8 times more cost effective” than CEA.⁷ 

As health care in the United States continues to evolve, we are faced with the issue of how best to spend limited resource dollars.

Is it practical or cost efficient to perform preventative surgery?

In England, an annual stroke rate of 2%-3% in a small subset of the population may be acceptable but we are not ready to concede that in the United States.  
For now, we will follow the SVS practice guidelines for the management of ACS as they are evidenced based and definitive.

CEA in conjunction with medical therapy remains the best way to prevent stroke in patients with severe  (>70%) ACS.

Dr. Conrad is  an assistant professor of surgery, Harvard Medical School, Boston. Dr. Cambria is The Robert R. Linton MD Professor of Vascular and Endovascular Surgery, Harvard Medical School, Boston.

References

1.Neurology. 2006;67:1390-1395
2.Circulation. 2012;125:188-197
3.N Engl J of Med. 1986;315:860-865
4.JAMA. 1995;273:1421-1428
5.Lancet. 2010;376:1074-1084
6.Journal of Vascular Surgery. 2011;54:e1-31
7.Stroke. 2009;40:e573-583
8.N Engl J Med. 2000;342:1693-1700
9. Eur J Vasc Endovasc Surg. 2005;30:275-284
10.Stroke. 2005;36:1128-1133
11. Stroke. 2007;38:1470-1475
12. Lancet. 2004;363:1491-1502

POINT: Medical treatment ends need for CEA or CAS.

By Anne L. Abbott, M.D.

The medical profession and the wider community must be congratulated upon their sustained efforts over recent decades that have seen an 80% fall in the average annual risk of stroke associated with moderate and severe (50%-99%) asymptomatic carotid stenosis (ACS).^1-6 This has been achieved by better medical treatment which consists of encouraging healthy lifestyle habits and appropriate use of medication. This major impact results from the combined effect of addressing all vascular risk factors in individual patients and efforts to use the best medical treatment available at the time. Rates are now so low (around 0.5% per year for ipsilateral stroke) that procedures, such as carotid endarterectomy (CEA), are now more likely to harm than help patients.⁷

Even if procedures were always completely risk-free, improved medical treatment may mean we have now reached the point where carotid procedures for ACS are safe but essentially ineffective for reducing stroke risk. The latest measurements of stroke risk using medical treatment alone indicate that only about 2.5% of patients with 50%-99% ACS will have a an ipsilateral stroke due to the carotid lesion during their remaining lifetime if they are receiving pretty good quality, current medical treatment alone. This is because the average age of identifying patients with ACS in past studies was about 70 years and the average survival following diagnosis was 10 years.¹ Further, only about half the strokes occurring in the distribution of an internal carotid artery with >60% proximal stenosis are due to the carotid lesion.⁸

Guidelines recommendations for CEA for 50%-99% or 60%-99% ACS rely on marginal, 20- to 30-year-old differences in stroke rates between patients given medical treatment alone versus those given additional CEA in best practice settings.^9-11  Such recommendations are not relevant to current clinical practice largely because the medical treatment used in these studies is obsolete. Multiple independent observations regarding the improved stroke prevention efficacy of medical treatment,^1-6,12 and the additional observations below, provide ample evidence that current medical treatment alone is the only routine-practice (nontrial) approach we should use for  patients with 50%-99% ACS and any future role of carotid procedures in these patients could only apply to very small minority subgroups:

i. Current optimal medical treatment for patients with ACS has not been defined nor its impact measured. This means that it is likely we can lower the risk of stroke and other vascular complications in patients with ACS stenosis even further than has been achieved in the most recent studies. The definition of current optimal medical treatment will vary from patient to patient depending on which vascular risk factors they have and what has been shown effective in modifying these to reduce the risk of any complications of vascular disease.

ii. The 30-day peri-operative risk of stroke or death (and other significant complications) remains above 0% in the most recent results of trials and registries^13-15 and is usually not measured in routine practice. Latest measurements of average annual ipsilateral stroke risk with medical treatment alone are about 2-3 times lower than for patients who had CEA or CAS in the Asymp tomatic Carotid Atherosclerosis Study (ACAS)10 or the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).^{7, 13}

iii. Patients with 50%-99% ACS receiving current optimal medical treatment and with a sufficiently high average annual risk of ipsilateral stroke, indicating they may benefit from CEA, have not been identified. This rate would need to be in excess of at least 2.5%-3.0%, using results from ACAS,¹⁰ to expect any surgical benefit in routine practice. Studies of baseline degree of  ACS within the 50%-99% range,^10,11,16 plaque echolucency¹⁷ and most studies of detecting asymptomatic stenosis progression18-21 show that these parameters (used separately) confer a relative risk of stroke of only about 2.0-2.5. Therefore, a higher degree of baseline stenosis within the 50%-99% range, the detection of predominantly echolucent carotid plaques  or asymptomatic progression are too weak on their own to identity patients likely to benefit from an additional carotid procedure. Combinations of risk markers are required for sufficient risk discrimination. For instance, results from the Asymptomatic Carotid Stenosis and Risk of Stroke Study (largest study so far of medically managed patients with moderate or severe ACS) showed that a combination of clinical features, baseline degree of stenosis and standardized ultrasonic plaque characteristics can achieve average annual ipsilateral stroke risk stratification ranging  from <1.0% to 10%.¹⁶ However, like all stroke risk stratification studies performed so far, this study was performed before the era of current medical treatment and the results have not been independently tested.

iv. Even if patients with sufficiently higher than average annual risk of ipsilateral stroke are one day reliably identified, randomized trials of an additional carotid procedure will be required to determine if, and to what extent, that procedure is likely to reduce ipsilateral stroke risk in routine practice.

v. The available evidence from randomized trials and registries indicates that CAS causes about twice as many strokes or deaths as surgery (just like it does for symptomatic carotid stenosis). Therefore, currently CAS cannot be recommended.⁷  In conclusion, the available evidence clearly indicates that current medical treatment alone now offers the best chance of reducing the risk of ipsilateral stroke in patients with 50%-99% ACS. There is no current evidence of benefit from CEA or CAS in these patients overall, or in any particular subgroups. However, there is much evidence regarding procedural risk and unaffordable cost.  Risk of ipsilateral stroke is now so low without carotid procedures it is time to shift from the historic approach of identifying ACS primarily to administer CEA. Rather, it is time to properly recognize that carotid stenosis is a risk factor of all complications of vascular disease, more than it is for ipsilateral stroke.²²

The priority is to define current optimal medical treatment as best we can, recognising that patients with ACS are a risk-heterogenous population. Then we need quality independent measurements of its impact on risk of all vascular disease complications using quality prospective cohort studies. Risk stratification models should be used to identify those who may benefit from trials of more intensive medical treatment, motivational strategies, plus/minus the safest carotid procedures. If identifying patients with ACS for CEA in routine practice is to be feasible, this needs to be done within well organized environments that support patients with a wide range of stenosis severity with the primary aim of implementing current optimal medical treatment to prevent all vascular complications. Finally, it must be accepted that as medical treatment and its implementation continue to improve, the added value of carotid procedures, including for symptomatic carotid stenosis, will continue to recede until we can say, ‘good job - it is finally fixed and it is time to move on to other major health issues.’

Dr. Abbott is a neurologist and an associate professor at Monash University, Melbourne, Australia.

References

1. Stroke. 2009;40:e573-583
2. Eur J Vasc Endovasc Surg. 2009;37:625-632
3. Nat Rev Cardiol. 2011;9:116-124
4. Stroke. 2013;44
5. Management of asymptomatic carotid stenosis: Technology assessment report. 2012:83
6. Annals of Internal Medicine. 2013;158:676-685
7. Stroke. 2013;44:1186-1190
8. N Engl J Med. 2000;342:1693-1700
9. N Engl J Med. 1993;328:221-227.
10.JAMA. 1995;273:1421-1428
11. Lancet. 2004;363:1491-1502
12. Arch Neurol. 2010;67:180-186
13. N Engl J Med. 2010;363:11-23
14. J Vasc Surg. 2009;49:71-79
15. J Vasc Surg. 2011;53:307-315
16. J Vasc Surg. 2010;52:1486-1496 e1481-1485
17. Gupta A, Kesavabhotla K, Barbadaran H, Kamel H, Panda A, Giambrone A, et al. Plaque echolucency and stroke risk in asymptoamtioc carotid stenosis: A systematic review and meta-analysis. Stroke. 2014 in press.
18. J Vasc Surg. 1999;29:208-214; discussion 214-206
19. J Vasc Surg. 2013;58:128-135 e121
20  Stroke. 2013;44:792-794
21. J Vasc Surg. 2014;59:956-967
22. N Engl J Med. 1986;315:860-865.

COUNTERPOINT: Medical therapy alone is not always enough.

By Mark F. Conrad, M.D., M.MSc., and Richard P. Cambria M.D.

Stroke remains the 3rd leading cause of death in the United States.¹  It is estimated that 10% to 20% of ischemic strokes can be attributed to an ipsilateral, typically high-grade carotid stenosis, thus, asymptomatic carotid bifurcation stenosis remains a potentially significant public health problem.²  Epidemiologic studies indicate that 5% to 6% of the population >65 years of age will harbor an asymptomatic and potentially surgically significant carotid stenosis.¹  The modern literature linking the degree of stenosis of the internal carotid artery and risk of ipsilateral stroke dates to the natural history studies of Chambers and Norris published in the New England Journal of Medicine in 1986.³  These investigators demonstrated a significant correlation of stroke risk with a >70% ipsilateral carotid artery stenosis and progression under observation. 

Carotid endarterectomy (CEA) has been the standard of care for the prevention of stroke in patients with severe (>70%) asymptomatic carotid artery stenosis (ACS) for five decades.  This is supported by level 1 evidence from multiple randomized trials^{4, 5} and consensus guideline recommendations.^{2, 6}  Yet the use of CEA in patients with ACS has been recently challenged by a widely publicized review article⁷ whose author has embarked upon an anti-CEA crusade with the zealous fervor of one who worships at the altar of the statin.  In this review, 11 prospective studies of medical therapy of patients with ACS (defined by the author as >50% stenosis) were stratified by date of publication such that the four series published from 2000-2007 had a lower raw data stroke rate with medical management (.6- 1.3%) than the 1.5% stroke rate reported after CEA in the ACAS study.^4,7  The authors concluded that medical management alone is “at least 3-8” times more cost effective than CEA despite a complete lack of cost data in the cited articles.   In an effort to debunk this revisionist history, we will begin by addressing the four aforementioned trials and finish with a discussion of the recent literature including an observational study from our own institution.

The first study of the four followed the asymptomatic contralateral carotid artery of all patients enrolled in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) for 5 years to determine the risk of stroke in medically managed patients.⁸  There were 2,377 patients of whom 216 (9%) had a stenosis >60% but only 113 (4.7%) had a stenosis of 75-99%.  The 5-year risk of ipsilateral stroke in the 75-99% asymptomatic stenosis cohort was 18.5% or 3.7% per year (this did not include other neurologic events such as TIA or amaurosis fugax).⁸  However, in the meta-analysis, no stroke rate was included in the raw data column (which was the basis of the final calculated overall stroke risk) and the final estimate quoted used the 60%-99% cohort such that the annual stroke rate was reported as 3.2%.⁷

The Asymptomatic Carotid Stenosis and Risk of Ipsilateral Hemispheric Ischemic Events Study (ACSRS) was a multicenter study that followed 1,115 patients with ACS >50% by duplex scanning for 6-84 months (mean 37.1) with the goal of stratifying patients into cohorts of high and low risk for future neurologic events.⁹  They concluded that the annual stroke rate in high-risk patients was 4.3% versus 0.7% in low-risk patients.  There were 453 patients with 70%-99% stenosis by NASCET criteria with a raw stroke rate of 5.7% (1.9%/ year over an average 3-year follow-up) and a 5-year ipsilateral event rate of about 18%.⁹  However, when the patients with 50-69% were added, the raw stroke rate decreased to 1.3%.⁷

The Asymptomatic Stenosis Embolus Detection (ASED) study was a prospective trial that tested the theory that transcranial Doppler embolic signal detection would identify increased risk of ipsilateral neurologic events in patients with >60% ACS.¹⁰  Of the 240 arteries studied, 115 (48%) had a stenosis of 70%-99% but 10 of these patients were censored because they underwent CEA during the follow-up period.  Their outcomes were not further stratified by degree of stenosis but the average ipsilateral carotid event rate was 3.1% per year with a 1% stroke risk per year.^{7, 10}

The final, and most damning study in the meta-analysis, included a cohort of patients from the Second Manifestations of Arterial disease (SMART) study which is a registry of patients from the Netherlands with risk factors for, or symptoms of, arterial disease.

 This study attempted to determine the risk of new vascular event in patients with ACS but 996 (27% of the registry) patients with a history of cerebrovascular disease (undefined) were excluded from analysis.¹¹  They identified 221 patients (8% of 2684 eligible patients) with ACS >50% and reported an ipsilateral stroke event rate of .6%/year.⁷ 

However, in the 147 patients with a 70-99% stenosis, the hazard ratio for ischemic stroke was 1.7 but it was not possible to separate the patients with a moderate (50-69%) stenosis from the outcomes of those with more severe (>70%) disease.¹¹ 

The major flaw with this study is that the authors excluded the 996 patients with a history of cerebrovascular disease who were at highest risk of having an ACS and subsequently suffering a stroke.

The flaw with combining the results of the above studies to conclude that medical therapy is the best way to prevent stroke in patients with severe ACS is that only half (828/1,754, 47%) of the patients included had a severe (70-99%) stenosis that would warrant CEA in the United States.^{6, 7}

The majority of the patients studied would have been treated with best medical therapy and serial Duplex scanning. Indeed, when the moderate patients were excluded, the yearly stroke rates for patients with actual severe stenosis ranged from 2.0%-3.7%; substantially higher than the 1.5% stroke rate associated with CEA.^{8, 9}

Randomized prospective trials such as the asymptomatic carotid artery stenosis (ACAS) study published in 1995 and the more recently updated asymptomatic carotid surgery trial (ACST) indicated a quite similar annual stroke risk in the 2% range for patients treated with medical therapy as opposed to those randomized to carotid endarterectomy (this study was excluded from the meta-analysis because patients with a remote (>6 months before entry) history of neurologic events were included).^4,12 In addition, the 10-year follow-up data in the ACST trial demonstrated a sustained benefit for endarterectomy over optimal medical therapy.⁵ It is important to emphasize that in this trial some 80% of patients were on optimal medical therapy (aspirin plus statin agents) in the later years of the trial.

These long-term data indicate that while the protective effect of endarterectomy was more pronounced in those not on appropriate lipid-lowering therapy (the 10-year advantage of endarterectomy over medical therapy in the prevention of stroke was 5.8% in patients taking a statin and 6.2% in those who were not)  the protective effect of endarterectomy over optimal medical therapy was statistically significant (P=0.002).⁵

This is of course relevant because clinicians in the modern era have typically used data from ACST to counsel patients about the stroke risk of asymptomatic high-grade carotid stenosis.

Finally, we followed at a cohort of 115 patients with severe (>70%) ACS who did not undergo CEA for a variety of reasons.

The average follow-up was 27 months and 86% of patients were on statin therapy. 

The 5-year ipsilateral ischemic event rate was 30%, and 48% of these were strokes.  When stratified by degree of stenosis, the patients with a 90%-99% stenosis had an ipsilateral neurologic event rate of 55%. This is a single center experience but the stroke rate of 3% per year is consistent with contemporary series and reiterates the reality of this risk for medically treated patients.

The question remains. When the efficacy of a CEA for the prevention of stroke in patients with ACS is supported by level 1 evidence from multiple prospective, randomized trials, why would anyone who treats patients with carotid disease allow a meta-analysis of natural history studies (that redefines a severe stenosis as >50%) convince them otherwise?

We believe that the answer lies in the unsubstantiated conclusion that “current medical intervention was estimated at least 3 to 8 times more cost effective” than CEA.⁷ 

As health care in the United States continues to evolve, we are faced with the issue of how best to spend limited resource dollars.

Is it practical or cost efficient to perform preventative surgery?

In England, an annual stroke rate of 2%-3% in a small subset of the population may be acceptable but we are not ready to concede that in the United States.  
For now, we will follow the SVS practice guidelines for the management of ACS as they are evidenced based and definitive.

CEA in conjunction with medical therapy remains the best way to prevent stroke in patients with severe  (>70%) ACS.

Dr. Conrad is  an assistant professor of surgery, Harvard Medical School, Boston. Dr. Cambria is The Robert R. Linton MD Professor of Vascular and Endovascular Surgery, Harvard Medical School, Boston.

References

1.Neurology. 2006;67:1390-1395
2.Circulation. 2012;125:188-197
3.N Engl J of Med. 1986;315:860-865
4.JAMA. 1995;273:1421-1428
5.Lancet. 2010;376:1074-1084
6.Journal of Vascular Surgery. 2011;54:e1-31
7.Stroke. 2009;40:e573-583
8.N Engl J Med. 2000;342:1693-1700
9. Eur J Vasc Endovasc Surg. 2005;30:275-284
10.Stroke. 2005;36:1128-1133
11. Stroke. 2007;38:1470-1475
12. Lancet. 2004;363:1491-1502

The presence of competing risks and overall lower levels of provider proficiency appeared to limit the benefits of carotid artery stenting in Medicare beneficiaries, according to the results of a large retrospective cohort study of the Centers for Medicare & Medicaid Services CAS database (2005-2009).

Periprocedural mortality was more than twice the rate in this patient population than in those earlier patients those involved in the pivotal CREST and SAPPHIRE clinical trials, according to a report published online Jan. 12 in JAMA Neurology [doi:10.1001/jamaneurol.2014.3638].

“The higher risk of periprocedural complications and the burden of competing risks owing to age and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries,” according to Jessica J. Jalbert, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues.

Over 22,000 patients were assessed in the study. The mean patient age was just over 76 years, 60.5% were men, and 94% were white. Approximately half were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%.

Almost 80% of the patients undergoing carotid artery stenting (CAS) met the SAPPHIRE trial indications and about half met at least one of the SAPPHIRE criteria for high surgical risk.

In the mean follow-up of approximately 2 years, mortality risks exceeded one-third for patients who were 80 years of age or older (41.5% mortality risk), symptomatic (37.3% risk), at high surgical risk with symptomatic carotid stenosis of at least 50% (37.3% risk), or admitted nonelectively (36.2% risk). In addition, among asymptomatic patients, mortality after the periprocedural period exceeded one-third for patients at least 80 years old.

Of particular concern, few of these Medicare beneficiaries undergoing CAS as per the National Coverage Determinations were treated by providers with proficiency levels similar to those required in the clinical trials. This is a potential problem because lower annual volume and early operator experience are associated with increased periprocedural mortality, the authors wrote.

CAS was performed primarily by male physicians (98.4%), specializing in cardiology (52.9%), practicing within a group (79.4%), and residing in the South (42.5%). The mean number of past-year CAS procedures performed was only 13.9 for physicians and 29.8 for hospitals. This translated to more than 80% of the physicians not meeting the minimum CAS volume requirements and/or minimum complication rates of the SAPPHIRE trial, and more than 90% not meeting the requirements of the CREST trial.

“Our results may support concerns about the limited generalizability of [randomized clinical trial] findings,” the researchers stated.

“Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries,” Dr. Jalbert and her colleagues concluded.

The authors reported no relevant disclosures. The study was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services.

[email protected]

The presence of competing risks and overall lower levels of provider proficiency appeared to limit the benefits of carotid artery stenting in Medicare beneficiaries, according to the results of a large retrospective cohort study of the Centers for Medicare & Medicaid Services CAS database (2005-2009).

Periprocedural mortality was more than twice the rate in this patient population than in those earlier patients those involved in the pivotal CREST and SAPPHIRE clinical trials, according to a report published online Jan. 12 in JAMA Neurology [doi:10.1001/jamaneurol.2014.3638].

“The higher risk of periprocedural complications and the burden of competing risks owing to age and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries,” according to Jessica J. Jalbert, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues.

Over 22,000 patients were assessed in the study. The mean patient age was just over 76 years, 60.5% were men, and 94% were white. Approximately half were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%.

Almost 80% of the patients undergoing carotid artery stenting (CAS) met the SAPPHIRE trial indications and about half met at least one of the SAPPHIRE criteria for high surgical risk.

In the mean follow-up of approximately 2 years, mortality risks exceeded one-third for patients who were 80 years of age or older (41.5% mortality risk), symptomatic (37.3% risk), at high surgical risk with symptomatic carotid stenosis of at least 50% (37.3% risk), or admitted nonelectively (36.2% risk). In addition, among asymptomatic patients, mortality after the periprocedural period exceeded one-third for patients at least 80 years old.

Of particular concern, few of these Medicare beneficiaries undergoing CAS as per the National Coverage Determinations were treated by providers with proficiency levels similar to those required in the clinical trials. This is a potential problem because lower annual volume and early operator experience are associated with increased periprocedural mortality, the authors wrote.

CAS was performed primarily by male physicians (98.4%), specializing in cardiology (52.9%), practicing within a group (79.4%), and residing in the South (42.5%). The mean number of past-year CAS procedures performed was only 13.9 for physicians and 29.8 for hospitals. This translated to more than 80% of the physicians not meeting the minimum CAS volume requirements and/or minimum complication rates of the SAPPHIRE trial, and more than 90% not meeting the requirements of the CREST trial.

“Our results may support concerns about the limited generalizability of [randomized clinical trial] findings,” the researchers stated.

“Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries,” Dr. Jalbert and her colleagues concluded.

The authors reported no relevant disclosures. The study was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services.

[email protected]

The presence of competing risks and overall lower levels of provider proficiency appeared to limit the benefits of carotid artery stenting in Medicare beneficiaries, according to the results of a large retrospective cohort study of the Centers for Medicare & Medicaid Services CAS database (2005-2009).

Periprocedural mortality was more than twice the rate in this patient population than in those earlier patients those involved in the pivotal CREST and SAPPHIRE clinical trials, according to a report published online Jan. 12 in JAMA Neurology [doi:10.1001/jamaneurol.2014.3638].

“The higher risk of periprocedural complications and the burden of competing risks owing to age and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries,” according to Jessica J. Jalbert, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues.

Over 22,000 patients were assessed in the study. The mean patient age was just over 76 years, 60.5% were men, and 94% were white. Approximately half were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%.

Almost 80% of the patients undergoing carotid artery stenting (CAS) met the SAPPHIRE trial indications and about half met at least one of the SAPPHIRE criteria for high surgical risk.

In the mean follow-up of approximately 2 years, mortality risks exceeded one-third for patients who were 80 years of age or older (41.5% mortality risk), symptomatic (37.3% risk), at high surgical risk with symptomatic carotid stenosis of at least 50% (37.3% risk), or admitted nonelectively (36.2% risk). In addition, among asymptomatic patients, mortality after the periprocedural period exceeded one-third for patients at least 80 years old.

Of particular concern, few of these Medicare beneficiaries undergoing CAS as per the National Coverage Determinations were treated by providers with proficiency levels similar to those required in the clinical trials. This is a potential problem because lower annual volume and early operator experience are associated with increased periprocedural mortality, the authors wrote.

CAS was performed primarily by male physicians (98.4%), specializing in cardiology (52.9%), practicing within a group (79.4%), and residing in the South (42.5%). The mean number of past-year CAS procedures performed was only 13.9 for physicians and 29.8 for hospitals. This translated to more than 80% of the physicians not meeting the minimum CAS volume requirements and/or minimum complication rates of the SAPPHIRE trial, and more than 90% not meeting the requirements of the CREST trial.

“Our results may support concerns about the limited generalizability of [randomized clinical trial] findings,” the researchers stated.

“Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries,” Dr. Jalbert and her colleagues concluded.

The authors reported no relevant disclosures. The study was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services.

[email protected]

SAN FRANCISCO – Patients undergoing carotid endarterectomy and open abdominal aortic aneurysm repair are less likely to have complications and die if their surgeon is a vascular specialist, according to a study reported at the annual clinical congress of the American College of Surgeons.

“We feel that carotid endarterectomy and open triple-A repair performed by a vascular surgeon is an independent predictor of improved morbidity and mortality. Hospitals should consider utilizing this specialty-specific information to identify potential quality improvement initiatives,” recommended lead investigator Dr. Carla C. Moreira, a surgeon in the division of vascular and endovascular surgery, Boston Medical Center.

She and her colleagues analyzed data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), assessing outcomes for 94,029 patients who underwent open vascular procedures between 2006 and 2012. Some 8% had abdominal aneurysm repairs, 57% had carotid endarterectomies, and 35% had lower-extremity bypasses.

Overall, 94% of the procedures were performed by vascular surgeons, while the rest were performed by other types of surgeons (including cardiac surgeons because their numbers were too small to tease out, according to Dr. Moreira).

Results showed that for patients undergoing abdominal aneurysm repair, the unadjusted rate of 30-day mortality did not differ significantly by surgeon specialty. However, in multivariate, propensity-matched analysis, the odds of complications were reduced by half when the repair was done by a vascular surgeon as compared with some other type of surgeon (odds ratio, 0.50).

Patients undergoing carotid endarterectomy had a lower unadjusted mortality if the operation was performed by a vascular surgeon (0.7% vs. 1.0%), although the difference was no longer significant after multivariate adjustment. However, they had significantly lower adjusted odds of complications (odds ratio, 0.62).

For patients undergoing lower-extremity bypass, neither the rate of mortality nor the odds of complications differed significantly by surgeon specialty.

An analysis of temporal trends showed that the proportions of all eligible patients undergoing open abdominal aneurysm repair and lower-extremity bypass during the study period fell, regardless of surgeon type, whereas the proportion of eligible patients undergoing carotid endarterectomies remained stable. “I think this is reflective likely of the penetration of endovascular procedures when it comes to the treatment of abdominal aneurysm and lower-extremity peripheral arterial disease, as compared to carotid disease,” speculated Dr. Moreira, who disclosed that she had no relevant conflicts of interest.

Session moderator Dr. Peter K. Henke, associate chair of research, department of surgery, and Leland Ira Doan Professor of Vascular Surgery at the University of Michigan in Ann Arbor, asked whether the findings have implications for surgeon training.

“Our results were different from what has been previously published for open aneurysm repair. I think that open aneurysm repair is probably becoming more and more specialized in terms that more and more, you are going to see just vascular surgeons performing it as compared to other specialties, especially as I have shown that there is a decreasing number of general surgeons being exposed to open vascular procedures,” Dr. Moreira replied. “So I think this [speaks] to individual surgeons and their individual experience with triple-A repair. Our data does show that general surgeons who are performing these procedures are doing a good job because there is not a difference in outcome at least in terms of mortality. But as the easy triple-A repairs go away, I think it’s going to push the procedure to be done more by specialized surgeons.”

In an interview, Dr. Henke commented, “I think it has been alluded to in other studies and other reports in the literature, but this study brings to the forefront the fact that overall numbers of open vascular procedures are less and less, so the surgeons performing those procedures need to be specialists. And I’d say within the U.S. anyway, most practitioners who do vascular procedures are vascular surgeons or cardiovascularly trained, as compared with general surgeons. I suspect that some of the general surgeons who are still doing these procedures may be at a place where they are the only ones who can do it or there are no vascular specialists there.

“The other issue that this study may impact, as more of these reports come out, is hospital credentialing, because hospital credentialing of surgeons really determines what they can and cannot do at that hospital,” he added. “So as more hospital credentialing boards see this type of data, I think they will limit open vascular procedures to vascular specialists who have had training in vascular disease.”

SAN FRANCISCO – Patients undergoing carotid endarterectomy and open abdominal aortic aneurysm repair are less likely to have complications and die if their surgeon is a vascular specialist, according to a study reported at the annual clinical congress of the American College of Surgeons.

“We feel that carotid endarterectomy and open triple-A repair performed by a vascular surgeon is an independent predictor of improved morbidity and mortality. Hospitals should consider utilizing this specialty-specific information to identify potential quality improvement initiatives,” recommended lead investigator Dr. Carla C. Moreira, a surgeon in the division of vascular and endovascular surgery, Boston Medical Center.

She and her colleagues analyzed data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), assessing outcomes for 94,029 patients who underwent open vascular procedures between 2006 and 2012. Some 8% had abdominal aneurysm repairs, 57% had carotid endarterectomies, and 35% had lower-extremity bypasses.

Overall, 94% of the procedures were performed by vascular surgeons, while the rest were performed by other types of surgeons (including cardiac surgeons because their numbers were too small to tease out, according to Dr. Moreira).

Results showed that for patients undergoing abdominal aneurysm repair, the unadjusted rate of 30-day mortality did not differ significantly by surgeon specialty. However, in multivariate, propensity-matched analysis, the odds of complications were reduced by half when the repair was done by a vascular surgeon as compared with some other type of surgeon (odds ratio, 0.50).

Patients undergoing carotid endarterectomy had a lower unadjusted mortality if the operation was performed by a vascular surgeon (0.7% vs. 1.0%), although the difference was no longer significant after multivariate adjustment. However, they had significantly lower adjusted odds of complications (odds ratio, 0.62).

For patients undergoing lower-extremity bypass, neither the rate of mortality nor the odds of complications differed significantly by surgeon specialty.

An analysis of temporal trends showed that the proportions of all eligible patients undergoing open abdominal aneurysm repair and lower-extremity bypass during the study period fell, regardless of surgeon type, whereas the proportion of eligible patients undergoing carotid endarterectomies remained stable. “I think this is reflective likely of the penetration of endovascular procedures when it comes to the treatment of abdominal aneurysm and lower-extremity peripheral arterial disease, as compared to carotid disease,” speculated Dr. Moreira, who disclosed that she had no relevant conflicts of interest.

Session moderator Dr. Peter K. Henke, associate chair of research, department of surgery, and Leland Ira Doan Professor of Vascular Surgery at the University of Michigan in Ann Arbor, asked whether the findings have implications for surgeon training.

“Our results were different from what has been previously published for open aneurysm repair. I think that open aneurysm repair is probably becoming more and more specialized in terms that more and more, you are going to see just vascular surgeons performing it as compared to other specialties, especially as I have shown that there is a decreasing number of general surgeons being exposed to open vascular procedures,” Dr. Moreira replied. “So I think this [speaks] to individual surgeons and their individual experience with triple-A repair. Our data does show that general surgeons who are performing these procedures are doing a good job because there is not a difference in outcome at least in terms of mortality. But as the easy triple-A repairs go away, I think it’s going to push the procedure to be done more by specialized surgeons.”

In an interview, Dr. Henke commented, “I think it has been alluded to in other studies and other reports in the literature, but this study brings to the forefront the fact that overall numbers of open vascular procedures are less and less, so the surgeons performing those procedures need to be specialists. And I’d say within the U.S. anyway, most practitioners who do vascular procedures are vascular surgeons or cardiovascularly trained, as compared with general surgeons. I suspect that some of the general surgeons who are still doing these procedures may be at a place where they are the only ones who can do it or there are no vascular specialists there.

“The other issue that this study may impact, as more of these reports come out, is hospital credentialing, because hospital credentialing of surgeons really determines what they can and cannot do at that hospital,” he added. “So as more hospital credentialing boards see this type of data, I think they will limit open vascular procedures to vascular specialists who have had training in vascular disease.”

SAN FRANCISCO – Patients undergoing carotid endarterectomy and open abdominal aortic aneurysm repair are less likely to have complications and die if their surgeon is a vascular specialist, according to a study reported at the annual clinical congress of the American College of Surgeons.

“We feel that carotid endarterectomy and open triple-A repair performed by a vascular surgeon is an independent predictor of improved morbidity and mortality. Hospitals should consider utilizing this specialty-specific information to identify potential quality improvement initiatives,” recommended lead investigator Dr. Carla C. Moreira, a surgeon in the division of vascular and endovascular surgery, Boston Medical Center.

She and her colleagues analyzed data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), assessing outcomes for 94,029 patients who underwent open vascular procedures between 2006 and 2012. Some 8% had abdominal aneurysm repairs, 57% had carotid endarterectomies, and 35% had lower-extremity bypasses.

Overall, 94% of the procedures were performed by vascular surgeons, while the rest were performed by other types of surgeons (including cardiac surgeons because their numbers were too small to tease out, according to Dr. Moreira).

Results showed that for patients undergoing abdominal aneurysm repair, the unadjusted rate of 30-day mortality did not differ significantly by surgeon specialty. However, in multivariate, propensity-matched analysis, the odds of complications were reduced by half when the repair was done by a vascular surgeon as compared with some other type of surgeon (odds ratio, 0.50).

Patients undergoing carotid endarterectomy had a lower unadjusted mortality if the operation was performed by a vascular surgeon (0.7% vs. 1.0%), although the difference was no longer significant after multivariate adjustment. However, they had significantly lower adjusted odds of complications (odds ratio, 0.62).

For patients undergoing lower-extremity bypass, neither the rate of mortality nor the odds of complications differed significantly by surgeon specialty.

An analysis of temporal trends showed that the proportions of all eligible patients undergoing open abdominal aneurysm repair and lower-extremity bypass during the study period fell, regardless of surgeon type, whereas the proportion of eligible patients undergoing carotid endarterectomies remained stable. “I think this is reflective likely of the penetration of endovascular procedures when it comes to the treatment of abdominal aneurysm and lower-extremity peripheral arterial disease, as compared to carotid disease,” speculated Dr. Moreira, who disclosed that she had no relevant conflicts of interest.

Session moderator Dr. Peter K. Henke, associate chair of research, department of surgery, and Leland Ira Doan Professor of Vascular Surgery at the University of Michigan in Ann Arbor, asked whether the findings have implications for surgeon training.

“Our results were different from what has been previously published for open aneurysm repair. I think that open aneurysm repair is probably becoming more and more specialized in terms that more and more, you are going to see just vascular surgeons performing it as compared to other specialties, especially as I have shown that there is a decreasing number of general surgeons being exposed to open vascular procedures,” Dr. Moreira replied. “So I think this [speaks] to individual surgeons and their individual experience with triple-A repair. Our data does show that general surgeons who are performing these procedures are doing a good job because there is not a difference in outcome at least in terms of mortality. But as the easy triple-A repairs go away, I think it’s going to push the procedure to be done more by specialized surgeons.”

In an interview, Dr. Henke commented, “I think it has been alluded to in other studies and other reports in the literature, but this study brings to the forefront the fact that overall numbers of open vascular procedures are less and less, so the surgeons performing those procedures need to be specialists. And I’d say within the U.S. anyway, most practitioners who do vascular procedures are vascular surgeons or cardiovascularly trained, as compared with general surgeons. I suspect that some of the general surgeons who are still doing these procedures may be at a place where they are the only ones who can do it or there are no vascular specialists there.

“The other issue that this study may impact, as more of these reports come out, is hospital credentialing, because hospital credentialing of surgeons really determines what they can and cannot do at that hospital,” he added. “So as more hospital credentialing boards see this type of data, I think they will limit open vascular procedures to vascular specialists who have had training in vascular disease.”

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

Patients started on less costly generic statin drugs have significantly better adherence than those started on brand name statins, as well as improved cardiovascular outcomes, according to results from a study that looked at records from more than 90,000 Medicare patients aged 65 and older (mean age 75.6, 61% female) over a 2-year period.

The study, led by Joshua J. Gagne, Pharm.D., Sc.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, and published online Sept. 15 in Annals of Internal Medicine (doi:10.7326/M13-2942), found that the average portion of days covered under prescribed statin therapy was 77% for patients started on generic lovastatin, pravastatin, or simvastatin, and 71% for patients started on name brands of these medications (P < .001). Researchers pinpointed cost as the likeliest reason for the differences in adherence; mean copay in the study was $10 for generics and $48 for brand-name drugs.

©PhotoDisk

Dr. Gagne and colleagues also reported that patients on generics saw an 8% reduction in cardiovascular events (as measured by a composite outcome of hospitalization for an acute coronary syndrome, stroke, or all-cause mortality), compared with those on brand-name medications (hazard ratio, 0.92; 95% confidence interval, 0.86-0.99).

Dr. Gagne and colleagues called the difference in cardiovascular outcomes “commensurate with the expected effect” based on differences in adherence, while noting that theirs was the first study to demonstrate differences in health outcomes related to the dispensing of generic or brand-name statins. Most patients in the study (n = 83,731) were started on generics. Generic drug recipients were more likely to be women (62% vs. 54%), and brand-name statin recipients were more likely to be white (66% vs. 48%).

“In the setting of tiered copayments in typical pharmacy benefit designs, initiating a generic versus a brand-name statin seems to be associated with lower out-of-pocket costs, improved adherence to therapy, and improved clinical outcomes,” the researchers concluded (Ann. Int. Med. 2014;161:400-7. [doi:10.7326/M13-2942]).

Dr. Gagne and colleagues noted among the limitations of their study its nonrandomized design, the use of only three statins, and the fact that they could not determine who decided whether patients initiated a generic or brand-name drug, noting that many states require pharmacists to dispense generics unless a prescriber or patient requests otherwise. The results may not apply to patients with types of insurance other than Medicare, they noted.

Teva pharmaceuticals, a manufacturer of generic medications, sponsored the study; Dr. Gagne and a coauthor, Niteesh K. Choudhry, M.D., Ph.D., disclosed grant support from Teva, while three coauthors disclosed being employees of CVS Caremark, a major pharmacy benefits administrator.

Patients started on less costly generic statin drugs have significantly better adherence than those started on brand name statins, as well as improved cardiovascular outcomes, according to results from a study that looked at records from more than 90,000 Medicare patients aged 65 and older (mean age 75.6, 61% female) over a 2-year period.

The study, led by Joshua J. Gagne, Pharm.D., Sc.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, and published online Sept. 15 in Annals of Internal Medicine (doi:10.7326/M13-2942), found that the average portion of days covered under prescribed statin therapy was 77% for patients started on generic lovastatin, pravastatin, or simvastatin, and 71% for patients started on name brands of these medications (P < .001). Researchers pinpointed cost as the likeliest reason for the differences in adherence; mean copay in the study was $10 for generics and $48 for brand-name drugs.

©PhotoDisk

Dr. Gagne and colleagues also reported that patients on generics saw an 8% reduction in cardiovascular events (as measured by a composite outcome of hospitalization for an acute coronary syndrome, stroke, or all-cause mortality), compared with those on brand-name medications (hazard ratio, 0.92; 95% confidence interval, 0.86-0.99).

Dr. Gagne and colleagues called the difference in cardiovascular outcomes “commensurate with the expected effect” based on differences in adherence, while noting that theirs was the first study to demonstrate differences in health outcomes related to the dispensing of generic or brand-name statins. Most patients in the study (n = 83,731) were started on generics. Generic drug recipients were more likely to be women (62% vs. 54%), and brand-name statin recipients were more likely to be white (66% vs. 48%).

“In the setting of tiered copayments in typical pharmacy benefit designs, initiating a generic versus a brand-name statin seems to be associated with lower out-of-pocket costs, improved adherence to therapy, and improved clinical outcomes,” the researchers concluded (Ann. Int. Med. 2014;161:400-7. [doi:10.7326/M13-2942]).

Dr. Gagne and colleagues noted among the limitations of their study its nonrandomized design, the use of only three statins, and the fact that they could not determine who decided whether patients initiated a generic or brand-name drug, noting that many states require pharmacists to dispense generics unless a prescriber or patient requests otherwise. The results may not apply to patients with types of insurance other than Medicare, they noted.

Teva pharmaceuticals, a manufacturer of generic medications, sponsored the study; Dr. Gagne and a coauthor, Niteesh K. Choudhry, M.D., Ph.D., disclosed grant support from Teva, while three coauthors disclosed being employees of CVS Caremark, a major pharmacy benefits administrator.

Patients started on less costly generic statin drugs have significantly better adherence than those started on brand name statins, as well as improved cardiovascular outcomes, according to results from a study that looked at records from more than 90,000 Medicare patients aged 65 and older (mean age 75.6, 61% female) over a 2-year period.

The study, led by Joshua J. Gagne, Pharm.D., Sc.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, and published online Sept. 15 in Annals of Internal Medicine (doi:10.7326/M13-2942), found that the average portion of days covered under prescribed statin therapy was 77% for patients started on generic lovastatin, pravastatin, or simvastatin, and 71% for patients started on name brands of these medications (P < .001). Researchers pinpointed cost as the likeliest reason for the differences in adherence; mean copay in the study was $10 for generics and $48 for brand-name drugs.

©PhotoDisk

Dr. Gagne and colleagues also reported that patients on generics saw an 8% reduction in cardiovascular events (as measured by a composite outcome of hospitalization for an acute coronary syndrome, stroke, or all-cause mortality), compared with those on brand-name medications (hazard ratio, 0.92; 95% confidence interval, 0.86-0.99).

Dr. Gagne and colleagues called the difference in cardiovascular outcomes “commensurate with the expected effect” based on differences in adherence, while noting that theirs was the first study to demonstrate differences in health outcomes related to the dispensing of generic or brand-name statins. Most patients in the study (n = 83,731) were started on generics. Generic drug recipients were more likely to be women (62% vs. 54%), and brand-name statin recipients were more likely to be white (66% vs. 48%).

“In the setting of tiered copayments in typical pharmacy benefit designs, initiating a generic versus a brand-name statin seems to be associated with lower out-of-pocket costs, improved adherence to therapy, and improved clinical outcomes,” the researchers concluded (Ann. Int. Med. 2014;161:400-7. [doi:10.7326/M13-2942]).

Dr. Gagne and colleagues noted among the limitations of their study its nonrandomized design, the use of only three statins, and the fact that they could not determine who decided whether patients initiated a generic or brand-name drug, noting that many states require pharmacists to dispense generics unless a prescriber or patient requests otherwise. The results may not apply to patients with types of insurance other than Medicare, they noted.

Teva pharmaceuticals, a manufacturer of generic medications, sponsored the study; Dr. Gagne and a coauthor, Niteesh K. Choudhry, M.D., Ph.D., disclosed grant support from Teva, while three coauthors disclosed being employees of CVS Caremark, a major pharmacy benefits administrator.

Introduction

The U.S. Preventive Services Task Force has just published its latest guidance on carotid screening for asymptomatic disease, basically stating that it should not be done (see story page 1). In this Point-Counterpoint Dr. Zierler and Dr. Berland provide their views on this controversial issue. From my perspective the debate must revolve around the following questions: The gist of the USPSTF statement seems to be that screening is being performed only to detect patients with critical carotid stenosis so that an intervention (CEA or CAS) can be performed. However, shouldn’t screening also be used to identify atherosclerotic burden in order to prevent cardiovascular morbidity? Whatever the reasons for screening, should national health systems pay for screening? If not, what about individual physicians charging for screenings on selected/nonselected patients? What about free screenings? And as Dr. Zierler and Dr. Berland suggest, is screening getting a bad rap just because screening and subsequent CEA or CAS are being poorly performed? Finally, I wouldn\'t be surprised if some of the task force members have had their own carotids screened despite their negative recommendation. We would be interested in your viewpoint, so please take our online, interactive poll on our home page (bottom right) to weigh in on this important issue.

Dr. Russell Samson is the Medical Editor of Vascular Specialist.

YES: Screen, but screen well.

By Todd Berland, M.D.

Every patient with symptomatic carotid artery stenosis was asymptomatic the day before. The impact of stroke can be devastating, with a 20% mortality from the acute event and 40%-50% survival over the next 5 years. Of those surviving the initial event, a significant percentage of patients are unable to return to work, and up to 25% over the age of 65 require long-term institutional care.¹ There is no doubt that the emotional, financial, and societal burden of caring for stroke patients is significant. The Asymptomatic Carotid Atherosclerosis Study and the Asymptomatic Carotid Surgery Trial demonstrated a significant reduction in stroke in asymptomatic, high-grade carotid artery stenosis patients treated with carotid endarterectomy compared to medical management alone.^2,3 So wouldn’t it seem as if carotid artery screening would be beneficial?

The U.S. Preventive Services Task Force recommended against routine carotid screening because of its "high risk" and low reward. I believe that when a certified lab screens the appropriate population such as individuals over 55 with cardiovascular risk factors that include hypertension, diabetes, smoking, and hypercholesterolemia, and combines this with an intervention that has a low stroke and morbidity rate, then the balance is tipped and carotid screening becomes both low risk and high reward.

One of the problems with carotid ultrasound is that too many entrepreneurs have made a business of it. Suboptimal equipment is being used by uncertified technicians in medical offices and church parking lots all across this country. It’s no surprise that the false positives are going to be high in these situations. Also, when one combines all of the above with the screening of those who aren’t at risk, where the general prevalence of disease is low, it can be a recipe for disaster. This is going to lead to additional studies such as CT angiograms or possibly even cerebral angiograms, both of which have inherent risks.

Even though it’s possible to understand why the USPSTF may have concluded against routine screening, I believe that at-risk patients should be screened by a certified lab, and that physicians performing the interventions should be able to do so with low morbidity and mortality. Vascular surgeons have been marginalized over recent years as many others have become interested in finding and treating carotid disease. Most of us are either registered vascular technologists or registered physicians in vascular interpretation, and our labs are certified by the Intersocietal Accreditation Commission. We go through hours of continuing medical education in regard to vascular ultrasound, and our labs’ results are tested and certified for accuracy.

We need to convince insurance companies and the Centers for Medicare & Medicaid Services that these studies should be permitted only in certified labs and the results interpreted by certified physicians such as vascular surgeons.

Moreover, when indicated, the interventions should be carried out by vascular surgeons who are trained to perform both carotid endarter- ectomy and carotid artery stenting to be able to offer the patient the best individualized treatment.

Dr. Berland is director of outpatient vascular interventions at NYU Langone Medical Center.

References

1. Circulation 2012;125:188.

2. JAMA 1995:273:1421-8.

3. Lancet 2004;363:1491-502.

NO: General screening is not appropriate.

By R. Eugene Zierler, M.D.

To most vascular specialists, the concept of detecting asymptomatic carotid stenosis and intervening to prevent stroke makes intuitive sense, but is it consistent with the evidence? In 2007, the USPSTF concluded that the general asymptomatic adult population should not be screened for carotid stenosis, and this recommendation has been reiterated in a 2014 draft recommendation statement.^1,2 Other groups, including our own Society for Vascular Surgery, have published similar recommendations.^3,4

Arguments in favor of screening for asymptomatic carotid stenosis are often based on the results of randomized controlled trials such as the Asymptomatic Carotid Atherosclerosis Study, which was reported in 1995.⁵ However, while these trials are historically important, they are no longer clinically relevant. Surgical and catheter-based interventions for carotid atherosclerosis have evolved significantly in the last 2 decades, but the outcomes associated with modern intensive medical therapy have also improved dramatically.^6,7 It is not clear that carotid endarterectomy or stenting is superior to current medical management for asymptomatic carotid stenosis, and new trials such as the recently announced CREST-2 are designed to answer these important questions.

The relatively poor reliability and accuracy of duplex ultrasound as a screening test for carotid stenosis is a major theme in the USPSTF draft recommendations, but in spite of this criticism, carotid duplex scanning has served as a clinically valuable method for classifying the severity of carotid stenosis for more than 30 years.⁸ As pointed out by others, the best way to ensure quality in the vascular laboratory is to recognize the importance of certified vascular sonographers, accredited vascular laboratories, and qualified medical staff. But despite high-quality ultrasound testing, relying on carotid stenosis as a marker of stroke risk has significant limitations. While there is an association between the degree of carotid stenosis and risk of stroke, many patients with severe carotid stenosis do not have strokes and some with moderate stenosis do have strokes. For example, it was reported that 61% of the symptomatic patients in the North American Symptomatic Carotid Endarterectomy Trial had less than 50% carotid stenosis.⁹ This suggests that stenosis severity alone does not identify those patients who are at the highest risk for stroke. Fortunately, the concept of the "vulnerable plaque" is promising as a means for more accurate risk stratification, and features such as intraplaque hemorrhage and thin or ruptured fibrous caps do correlate with a high risk for stroke.¹⁰ Experience has shown that these features can be characterized by ultrasound.¹¹

So although screening of the general population for asymptomatic carotid stenosis is not justified, there still may be subgroups of patients with specific risk factors and plaque features that could benefit from early intervention, and future clinical trials will establish whether or not this hypothesis has merit. Until more data are available the issue of screening for asymptomatic carotid stenosis will continue to provoke debate on multiple levels. Carotid disease screening is not covered by insurance, so cost and ability to pay are key factors to consider. In these discussions, the health of the patient and the population must always be the first priority, and clinical decision-making should be evidence based.

Dr. Zierler is professor of surgery at the University of Washington and medical director of the D.E. Strandness Jr. Vascular Laboratory at the university’s medical center and Harborview Medical Center, Seattle. He is also an associate medical editor of Vascular Specialist.

References

1. Ann. Intern. Med. 2007;147:860-70.

2. uspreventiveservicestaskforce.org/.htm.

3. JACC 2011;57:e16-94.

4. J. Vasc. Surg. 2011;54:e1-31.

5. JAMA 1995:273:1421-8.

6. Circulation 2013;127:739-42.

7. Stroke 2009;40:e573-83.

8. Vasc. Endovascular Surg. 2012;46:466-74.

9. N. Engl. J. Med. 1998;339:1415-25.

10. Imaging Med. 2010;2:63-75.

11. J. Vasc. Surg. 2010;52:1486-96.

Introduction

The U.S. Preventive Services Task Force has just published its latest guidance on carotid screening for asymptomatic disease, basically stating that it should not be done (see story page 1). In this Point-Counterpoint Dr. Zierler and Dr. Berland provide their views on this controversial issue. From my perspective the debate must revolve around the following questions: The gist of the USPSTF statement seems to be that screening is being performed only to detect patients with critical carotid stenosis so that an intervention (CEA or CAS) can be performed. However, shouldn’t screening also be used to identify atherosclerotic burden in order to prevent cardiovascular morbidity? Whatever the reasons for screening, should national health systems pay for screening? If not, what about individual physicians charging for screenings on selected/nonselected patients? What about free screenings? And as Dr. Zierler and Dr. Berland suggest, is screening getting a bad rap just because screening and subsequent CEA or CAS are being poorly performed? Finally, I wouldn\'t be surprised if some of the task force members have had their own carotids screened despite their negative recommendation. We would be interested in your viewpoint, so please take our online, interactive poll on our home page (bottom right) to weigh in on this important issue.

Dr. Russell Samson is the Medical Editor of Vascular Specialist.

YES: Screen, but screen well.

By Todd Berland, M.D.

Every patient with symptomatic carotid artery stenosis was asymptomatic the day before. The impact of stroke can be devastating, with a 20% mortality from the acute event and 40%-50% survival over the next 5 years. Of those surviving the initial event, a significant percentage of patients are unable to return to work, and up to 25% over the age of 65 require long-term institutional care.¹ There is no doubt that the emotional, financial, and societal burden of caring for stroke patients is significant. The Asymptomatic Carotid Atherosclerosis Study and the Asymptomatic Carotid Surgery Trial demonstrated a significant reduction in stroke in asymptomatic, high-grade carotid artery stenosis patients treated with carotid endarterectomy compared to medical management alone.^2,3 So wouldn’t it seem as if carotid artery screening would be beneficial?

The U.S. Preventive Services Task Force recommended against routine carotid screening because of its "high risk" and low reward. I believe that when a certified lab screens the appropriate population such as individuals over 55 with cardiovascular risk factors that include hypertension, diabetes, smoking, and hypercholesterolemia, and combines this with an intervention that has a low stroke and morbidity rate, then the balance is tipped and carotid screening becomes both low risk and high reward.

One of the problems with carotid ultrasound is that too many entrepreneurs have made a business of it. Suboptimal equipment is being used by uncertified technicians in medical offices and church parking lots all across this country. It’s no surprise that the false positives are going to be high in these situations. Also, when one combines all of the above with the screening of those who aren’t at risk, where the general prevalence of disease is low, it can be a recipe for disaster. This is going to lead to additional studies such as CT angiograms or possibly even cerebral angiograms, both of which have inherent risks.

Even though it’s possible to understand why the USPSTF may have concluded against routine screening, I believe that at-risk patients should be screened by a certified lab, and that physicians performing the interventions should be able to do so with low morbidity and mortality. Vascular surgeons have been marginalized over recent years as many others have become interested in finding and treating carotid disease. Most of us are either registered vascular technologists or registered physicians in vascular interpretation, and our labs are certified by the Intersocietal Accreditation Commission. We go through hours of continuing medical education in regard to vascular ultrasound, and our labs’ results are tested and certified for accuracy.

We need to convince insurance companies and the Centers for Medicare & Medicaid Services that these studies should be permitted only in certified labs and the results interpreted by certified physicians such as vascular surgeons.

Moreover, when indicated, the interventions should be carried out by vascular surgeons who are trained to perform both carotid endarter- ectomy and carotid artery stenting to be able to offer the patient the best individualized treatment.

Dr. Berland is director of outpatient vascular interventions at NYU Langone Medical Center.

References

1. Circulation 2012;125:188.

2. JAMA 1995:273:1421-8.

3. Lancet 2004;363:1491-502.

NO: General screening is not appropriate.

By R. Eugene Zierler, M.D.

To most vascular specialists, the concept of detecting asymptomatic carotid stenosis and intervening to prevent stroke makes intuitive sense, but is it consistent with the evidence? In 2007, the USPSTF concluded that the general asymptomatic adult population should not be screened for carotid stenosis, and this recommendation has been reiterated in a 2014 draft recommendation statement.^1,2 Other groups, including our own Society for Vascular Surgery, have published similar recommendations.^3,4

Arguments in favor of screening for asymptomatic carotid stenosis are often based on the results of randomized controlled trials such as the Asymptomatic Carotid Atherosclerosis Study, which was reported in 1995.⁵ However, while these trials are historically important, they are no longer clinically relevant. Surgical and catheter-based interventions for carotid atherosclerosis have evolved significantly in the last 2 decades, but the outcomes associated with modern intensive medical therapy have also improved dramatically.^6,7 It is not clear that carotid endarterectomy or stenting is superior to current medical management for asymptomatic carotid stenosis, and new trials such as the recently announced CREST-2 are designed to answer these important questions.

The relatively poor reliability and accuracy of duplex ultrasound as a screening test for carotid stenosis is a major theme in the USPSTF draft recommendations, but in spite of this criticism, carotid duplex scanning has served as a clinically valuable method for classifying the severity of carotid stenosis for more than 30 years.⁸ As pointed out by others, the best way to ensure quality in the vascular laboratory is to recognize the importance of certified vascular sonographers, accredited vascular laboratories, and qualified medical staff. But despite high-quality ultrasound testing, relying on carotid stenosis as a marker of stroke risk has significant limitations. While there is an association between the degree of carotid stenosis and risk of stroke, many patients with severe carotid stenosis do not have strokes and some with moderate stenosis do have strokes. For example, it was reported that 61% of the symptomatic patients in the North American Symptomatic Carotid Endarterectomy Trial had less than 50% carotid stenosis.⁹ This suggests that stenosis severity alone does not identify those patients who are at the highest risk for stroke. Fortunately, the concept of the "vulnerable plaque" is promising as a means for more accurate risk stratification, and features such as intraplaque hemorrhage and thin or ruptured fibrous caps do correlate with a high risk for stroke.¹⁰ Experience has shown that these features can be characterized by ultrasound.¹¹

So although screening of the general population for asymptomatic carotid stenosis is not justified, there still may be subgroups of patients with specific risk factors and plaque features that could benefit from early intervention, and future clinical trials will establish whether or not this hypothesis has merit. Until more data are available the issue of screening for asymptomatic carotid stenosis will continue to provoke debate on multiple levels. Carotid disease screening is not covered by insurance, so cost and ability to pay are key factors to consider. In these discussions, the health of the patient and the population must always be the first priority, and clinical decision-making should be evidence based.

Dr. Zierler is professor of surgery at the University of Washington and medical director of the D.E. Strandness Jr. Vascular Laboratory at the university’s medical center and Harborview Medical Center, Seattle. He is also an associate medical editor of Vascular Specialist.

References

1. Ann. Intern. Med. 2007;147:860-70.

2. uspreventiveservicestaskforce.org/.htm.

3. JACC 2011;57:e16-94.

4. J. Vasc. Surg. 2011;54:e1-31.

5. JAMA 1995:273:1421-8.

6. Circulation 2013;127:739-42.

7. Stroke 2009;40:e573-83.

8. Vasc. Endovascular Surg. 2012;46:466-74.

9. N. Engl. J. Med. 1998;339:1415-25.

10. Imaging Med. 2010;2:63-75.

11. J. Vasc. Surg. 2010;52:1486-96.

Introduction

The U.S. Preventive Services Task Force has just published its latest guidance on carotid screening for asymptomatic disease, basically stating that it should not be done (see story page 1). In this Point-Counterpoint Dr. Zierler and Dr. Berland provide their views on this controversial issue. From my perspective the debate must revolve around the following questions: The gist of the USPSTF statement seems to be that screening is being performed only to detect patients with critical carotid stenosis so that an intervention (CEA or CAS) can be performed. However, shouldn’t screening also be used to identify atherosclerotic burden in order to prevent cardiovascular morbidity? Whatever the reasons for screening, should national health systems pay for screening? If not, what about individual physicians charging for screenings on selected/nonselected patients? What about free screenings? And as Dr. Zierler and Dr. Berland suggest, is screening getting a bad rap just because screening and subsequent CEA or CAS are being poorly performed? Finally, I wouldn\'t be surprised if some of the task force members have had their own carotids screened despite their negative recommendation. We would be interested in your viewpoint, so please take our online, interactive poll on our home page (bottom right) to weigh in on this important issue.

Dr. Russell Samson is the Medical Editor of Vascular Specialist.

YES: Screen, but screen well.

By Todd Berland, M.D.

Every patient with symptomatic carotid artery stenosis was asymptomatic the day before. The impact of stroke can be devastating, with a 20% mortality from the acute event and 40%-50% survival over the next 5 years. Of those surviving the initial event, a significant percentage of patients are unable to return to work, and up to 25% over the age of 65 require long-term institutional care.¹ There is no doubt that the emotional, financial, and societal burden of caring for stroke patients is significant. The Asymptomatic Carotid Atherosclerosis Study and the Asymptomatic Carotid Surgery Trial demonstrated a significant reduction in stroke in asymptomatic, high-grade carotid artery stenosis patients treated with carotid endarterectomy compared to medical management alone.^2,3 So wouldn’t it seem as if carotid artery screening would be beneficial?

The U.S. Preventive Services Task Force recommended against routine carotid screening because of its "high risk" and low reward. I believe that when a certified lab screens the appropriate population such as individuals over 55 with cardiovascular risk factors that include hypertension, diabetes, smoking, and hypercholesterolemia, and combines this with an intervention that has a low stroke and morbidity rate, then the balance is tipped and carotid screening becomes both low risk and high reward.

One of the problems with carotid ultrasound is that too many entrepreneurs have made a business of it. Suboptimal equipment is being used by uncertified technicians in medical offices and church parking lots all across this country. It’s no surprise that the false positives are going to be high in these situations. Also, when one combines all of the above with the screening of those who aren’t at risk, where the general prevalence of disease is low, it can be a recipe for disaster. This is going to lead to additional studies such as CT angiograms or possibly even cerebral angiograms, both of which have inherent risks.

Even though it’s possible to understand why the USPSTF may have concluded against routine screening, I believe that at-risk patients should be screened by a certified lab, and that physicians performing the interventions should be able to do so with low morbidity and mortality. Vascular surgeons have been marginalized over recent years as many others have become interested in finding and treating carotid disease. Most of us are either registered vascular technologists or registered physicians in vascular interpretation, and our labs are certified by the Intersocietal Accreditation Commission. We go through hours of continuing medical education in regard to vascular ultrasound, and our labs’ results are tested and certified for accuracy.

We need to convince insurance companies and the Centers for Medicare & Medicaid Services that these studies should be permitted only in certified labs and the results interpreted by certified physicians such as vascular surgeons.

Moreover, when indicated, the interventions should be carried out by vascular surgeons who are trained to perform both carotid endarter- ectomy and carotid artery stenting to be able to offer the patient the best individualized treatment.

Dr. Berland is director of outpatient vascular interventions at NYU Langone Medical Center.

References

1. Circulation 2012;125:188.

2. JAMA 1995:273:1421-8.

3. Lancet 2004;363:1491-502.

NO: General screening is not appropriate.

By R. Eugene Zierler, M.D.

To most vascular specialists, the concept of detecting asymptomatic carotid stenosis and intervening to prevent stroke makes intuitive sense, but is it consistent with the evidence? In 2007, the USPSTF concluded that the general asymptomatic adult population should not be screened for carotid stenosis, and this recommendation has been reiterated in a 2014 draft recommendation statement.^1,2 Other groups, including our own Society for Vascular Surgery, have published similar recommendations.^3,4

Arguments in favor of screening for asymptomatic carotid stenosis are often based on the results of randomized controlled trials such as the Asymptomatic Carotid Atherosclerosis Study, which was reported in 1995.⁵ However, while these trials are historically important, they are no longer clinically relevant. Surgical and catheter-based interventions for carotid atherosclerosis have evolved significantly in the last 2 decades, but the outcomes associated with modern intensive medical therapy have also improved dramatically.^6,7 It is not clear that carotid endarterectomy or stenting is superior to current medical management for asymptomatic carotid stenosis, and new trials such as the recently announced CREST-2 are designed to answer these important questions.

The relatively poor reliability and accuracy of duplex ultrasound as a screening test for carotid stenosis is a major theme in the USPSTF draft recommendations, but in spite of this criticism, carotid duplex scanning has served as a clinically valuable method for classifying the severity of carotid stenosis for more than 30 years.⁸ As pointed out by others, the best way to ensure quality in the vascular laboratory is to recognize the importance of certified vascular sonographers, accredited vascular laboratories, and qualified medical staff. But despite high-quality ultrasound testing, relying on carotid stenosis as a marker of stroke risk has significant limitations. While there is an association between the degree of carotid stenosis and risk of stroke, many patients with severe carotid stenosis do not have strokes and some with moderate stenosis do have strokes. For example, it was reported that 61% of the symptomatic patients in the North American Symptomatic Carotid Endarterectomy Trial had less than 50% carotid stenosis.⁹ This suggests that stenosis severity alone does not identify those patients who are at the highest risk for stroke. Fortunately, the concept of the "vulnerable plaque" is promising as a means for more accurate risk stratification, and features such as intraplaque hemorrhage and thin or ruptured fibrous caps do correlate with a high risk for stroke.¹⁰ Experience has shown that these features can be characterized by ultrasound.¹¹

So although screening of the general population for asymptomatic carotid stenosis is not justified, there still may be subgroups of patients with specific risk factors and plaque features that could benefit from early intervention, and future clinical trials will establish whether or not this hypothesis has merit. Until more data are available the issue of screening for asymptomatic carotid stenosis will continue to provoke debate on multiple levels. Carotid disease screening is not covered by insurance, so cost and ability to pay are key factors to consider. In these discussions, the health of the patient and the population must always be the first priority, and clinical decision-making should be evidence based.

Dr. Zierler is professor of surgery at the University of Washington and medical director of the D.E. Strandness Jr. Vascular Laboratory at the university’s medical center and Harborview Medical Center, Seattle. He is also an associate medical editor of Vascular Specialist.

References

1. Ann. Intern. Med. 2007;147:860-70.

2. uspreventiveservicestaskforce.org/.htm.

3. JACC 2011;57:e16-94.

4. J. Vasc. Surg. 2011;54:e1-31.

5. JAMA 1995:273:1421-8.

6. Circulation 2013;127:739-42.

7. Stroke 2009;40:e573-83.

8. Vasc. Endovascular Surg. 2012;46:466-74.

9. N. Engl. J. Med. 1998;339:1415-25.

10. Imaging Med. 2010;2:63-75.

11. J. Vasc. Surg. 2010;52:1486-96.

BOSTON – Asymptomatic carotid stenosis is associated with cognitive impairment when compared to patients with similar risk factors but no stenosis, said Dr. Brajesh K. Lal, of the University of Maryland, Baltimore.

Dr. Lal presented results from the Asymptomatic Carotid Stenosis and Cognitive Function (ACCOF) study. "The key finding is that we've identified for the first time unequivocally that an asymptomatic carotid artery plaque in a patient that has never suffered a stroke before can result in cognitive impairment," Dr. Lal said at the Vascular Annual Meeting.

Vascular comorbidities, such as diabetes, hypertension, coronary disease, and hyperlipidemia, are well known to cause vascular cognitive impairment (VCI), and this new research indicates that ACS should be added to that list, according to Dr. Lal and his colleagues.

They assessed 129 patients, 69 with greater than or equal to 50% ACS and 60 controls with vascular co-morbidities without ACS. An overall index of cognitive function and five domain-specific scores were computed. Breath-holding index (BHI), an estimate of cerebrovascular reserve, was measured using transcranial Doppler. Patients were assigned to high vs. low BHI groups using a cut-off score of 0.69. They assessed differences among stenosis vs. control patients and stenosis patients with low vs. high BHIs.

The stenosis and control groups did not differ with respect to vascular risk factors, IQ, educational attainment, and depressive symptoms. The stenosis group performed worse on the overall composite cognitive score and the domain-specific scores for processing speed and learning/memory, all significant differences. Within the stenosis group, those with low BHI performed significantly worse on learning, and trended lower on processing speed and overall composite score.

"The ACCOF study results showed that asymptomatic carotid stenosis is associated with cognitive impairment when compared to patients with similar risk factors but no stenosis. The deficit is driven primarily by reduced processing speed and learning/memory, and is mild to moderate in severity. A likely mechanism for this impairment is reduced cerebrovascular reserve," said Dr. Lal. "These findings have the potential to impact decision making in the management of patients with ACS."

[email protected]

BOSTON – Asymptomatic carotid stenosis is associated with cognitive impairment when compared to patients with similar risk factors but no stenosis, said Dr. Brajesh K. Lal, of the University of Maryland, Baltimore.

Dr. Lal presented results from the Asymptomatic Carotid Stenosis and Cognitive Function (ACCOF) study. "The key finding is that we've identified for the first time unequivocally that an asymptomatic carotid artery plaque in a patient that has never suffered a stroke before can result in cognitive impairment," Dr. Lal said at the Vascular Annual Meeting.

Vascular comorbidities, such as diabetes, hypertension, coronary disease, and hyperlipidemia, are well known to cause vascular cognitive impairment (VCI), and this new research indicates that ACS should be added to that list, according to Dr. Lal and his colleagues.

They assessed 129 patients, 69 with greater than or equal to 50% ACS and 60 controls with vascular co-morbidities without ACS. An overall index of cognitive function and five domain-specific scores were computed. Breath-holding index (BHI), an estimate of cerebrovascular reserve, was measured using transcranial Doppler. Patients were assigned to high vs. low BHI groups using a cut-off score of 0.69. They assessed differences among stenosis vs. control patients and stenosis patients with low vs. high BHIs.

The stenosis and control groups did not differ with respect to vascular risk factors, IQ, educational attainment, and depressive symptoms. The stenosis group performed worse on the overall composite cognitive score and the domain-specific scores for processing speed and learning/memory, all significant differences. Within the stenosis group, those with low BHI performed significantly worse on learning, and trended lower on processing speed and overall composite score.

"The ACCOF study results showed that asymptomatic carotid stenosis is associated with cognitive impairment when compared to patients with similar risk factors but no stenosis. The deficit is driven primarily by reduced processing speed and learning/memory, and is mild to moderate in severity. A likely mechanism for this impairment is reduced cerebrovascular reserve," said Dr. Lal. "These findings have the potential to impact decision making in the management of patients with ACS."

[email protected]

BOSTON – Asymptomatic carotid stenosis is associated with cognitive impairment when compared to patients with similar risk factors but no stenosis, said Dr. Brajesh K. Lal, of the University of Maryland, Baltimore.

Dr. Lal presented results from the Asymptomatic Carotid Stenosis and Cognitive Function (ACCOF) study. "The key finding is that we've identified for the first time unequivocally that an asymptomatic carotid artery plaque in a patient that has never suffered a stroke before can result in cognitive impairment," Dr. Lal said at the Vascular Annual Meeting.

Vascular comorbidities, such as diabetes, hypertension, coronary disease, and hyperlipidemia, are well known to cause vascular cognitive impairment (VCI), and this new research indicates that ACS should be added to that list, according to Dr. Lal and his colleagues.

They assessed 129 patients, 69 with greater than or equal to 50% ACS and 60 controls with vascular co-morbidities without ACS. An overall index of cognitive function and five domain-specific scores were computed. Breath-holding index (BHI), an estimate of cerebrovascular reserve, was measured using transcranial Doppler. Patients were assigned to high vs. low BHI groups using a cut-off score of 0.69. They assessed differences among stenosis vs. control patients and stenosis patients with low vs. high BHIs.

The stenosis and control groups did not differ with respect to vascular risk factors, IQ, educational attainment, and depressive symptoms. The stenosis group performed worse on the overall composite cognitive score and the domain-specific scores for processing speed and learning/memory, all significant differences. Within the stenosis group, those with low BHI performed significantly worse on learning, and trended lower on processing speed and overall composite score.

"The ACCOF study results showed that asymptomatic carotid stenosis is associated with cognitive impairment when compared to patients with similar risk factors but no stenosis. The deficit is driven primarily by reduced processing speed and learning/memory, and is mild to moderate in severity. A likely mechanism for this impairment is reduced cerebrovascular reserve," said Dr. Lal. "These findings have the potential to impact decision making in the management of patients with ACS."

[email protected]