Carotid Artery Stenting

INTRODUCTION

A guideline update on the management of patients with extracranial carotid artery disease was recently published.¹ The updated guidelines are based on the compilation of several randomized studies examining methods of revascularization in patients with extracranial carotid artery stenoses. This guideline statement is unique because it represents a true multidisciplinary consensus across several specialties in medicine. The document is endorsed by multiple professional societies including the American Heart Association, American College of Cardiology, American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society of Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery.

BACKGROUND

Stroke is an important cause of morbidity and mortality in the United States.² When considered separately from other cardiovascular diseases, stroke is ranked as the third most common cause of death in the country (heart disease ranks first; cancer ranks second). Stroke accounted for approximately 1 of every 17 deaths occurring in the United States in 2005. For patients who survive stroke, it can cause devastating disabilities.

Each year, approximately 795,000 Americans experience a stroke. Approximately 610,000 are initial attacks; and 185,000 are recurrent attacks. On average, every 40 seconds, someone in the United States suffers a stroke. Locally, stroke is a much more disturbing problem than it is nationally. Recent statistics rank the state of Oklahoma’s stroke death rate to be the forty-ninth worst in the country.²

Of all strokes, 87% are ischemic in etiology, and 13% are hemorrhagic in etiology.² Carotid artery disease is an important cause of ischemic stroke. The majority of ischemic strokes (59%) that occur in patients aged 45 to 70 years old are attributed to large artery atherosclerosis.³

LANDMARK CLINICAL TRIALS

The updated 2011 guidelines on the management of patients with extracranial carotid artery disease are inspired by several randomized studies examining the role of carotid artery revascularization.¹ Landmark clinical trials that have examined the role of carotid artery revascularization include the North American Symptomatic Carotid Endarterectomy Trial (NASCET),⁴ the Asymptomatic Carotid Atherosclerosis Study (ACAS),⁵ the Asymptomatic Carotid Surgery Trial (ACST),⁶ the Stenting and Angioplasty with Protection in Patients at HIgh Risk for Endarterectomy trial (SAPPHIRE)⁷ and the Carotid Revascularization Endarterectomy versus Stent Trial (CREST).⁸ These landmark clinical trials are briefly summarized here to familiarize the reader with their important findings.

NASCET⁴ was a multi-center, randomized, controlled trial of 2226 patients at 106 centers. The inclusion criteria included hemispheric or retinal transient ischemic attack or a nondisabling stroke within 120 days of entry. Patients were divided into two predetermined categories based on the severity of carotid stenosis: 30-69% and 70-99%. Patients were then randomly assigned to receive carotid endarterectomy or medical care alone. All patients received optimal medical care, including antiplatelet therapy. The risk of ipsilateral stroke was reduced significantly (p=0.045) in patients with carotid stenosis of 50-69% who received carotid endarterectomy. Patients with stenosis of 70-99% showed the most significant reduction (p < 0.001) in the rate of ipsilateral stroke while patients with stenosis of <50% did not show a significantly lower rate of ipsilateral stroke. NASCET validates the use of carotid endarterectomy in patients with symptomatic carotid artery disease to reduce the risk of stroke.

ACAS⁵ was a prospective, randomized, multicenter trial of 1662 patients at 39 centers. The inclusion criteria included asymptomatic carotid artery stenosis of 60% or greater reduction in diameter. Daily aspirin administration and medical risk factor management was required for all patients. Carotid endarterectomy was performed for patients randomized to receive surgery. Aggregate risk for ipsilateral stroke and any perioperative stroke or death was found to be 5.1% for surgical patients and 11.0% for patients treated medically.

ACST⁶ was an international, multi-center, prospective, randomized trial involving 3120 patients. Inclusion criteria included patients with unilateral or bilateral carotid stenosis considered appropriate for surgery who have experienced no ipsilateral transient ischemic attack, amaurosis fugax, or stroke within the past 6 months, and who have no history of ipsilateral disabling stroke or severe contralateral stroke. Eligible patients were randomized to receive either best medical therapy or best medical therapy combined with carotid endarterectomy. Comparing all patients randomized to immediate carotid endarterectomy versus all patients randomized to deferral (combining the perioperative events and non-perioperative strokes), the net 5 year stroke risks were 6.4% vs 11.8% for all strokes (net gain 5.4% [3.0-7.8], p < 0.0001) and 3.5% vs 6.1% for fatal or disabling strokes (net gain 2.5% [0.8-4.3], p < 0.004) and 2.1% vs 4.2% for only fatal strokes (net gain 2.1% [0.6-3.6], p=0.006).

ACAS and ACST validate the use of carotid endarterectomy in patients with significant asymptomatic carotid artery disease to reduce their risk of stroke.

SAPPHIRE⁷ was a multicenter trial which randomized 334 high risk patients to receive either carotid endarterectomy or the protective stenting procedure. The inclusion criteria included patients with symptomatic carotid-artery disease with >= 50% stenosis and patients with asymptomatic carotid-artery disease with >= 80 %, determined by color duplex ultrasonography. All patients were required to have at least one co-existing condition that potentially increased the risk posed by carotid endarterectomy (e.g., severe cardiac or pulmonary disease; age > 80, etc), but were judged potentially suitable for either endarterectomy or stenting. Treatment with aspirin at a dose of 81 or 325 mg per day was begun at least 72 hours before stenting or endarterectomy and was continued indefinitely in both study groups. Both groups received intraprocedural heparin to maintain a therapeutic activated partial-thromboplastin time of 250 to 300 seconds. Patients undergoing stenting received clopidogrel (75 mg per day) starting 24 hours before the procedure and continuing for two to four weeks thereafter. Patients undergoing endarterectomy did not receive clopidogrel. The primary end point (cumulative incidence of a major cardiovascular event at one year: a composite of death, stroke or myocardial infarction within 30 days of intervention or ipsilateral stroke between 31 days and 1 year) occurred in 20 patients randomly assigned to undergo carotid-artery stenting with an emboli-protection device (cumulative incidence, 12.2%) and in 32 patients randomly assigned to undergo carotid endarterectomy (cumulative incidence, 20.1%, absolute difference, 7.9%; 95 percent confidence interval, 16.4 to 0.7 %; P=0.004 for noninferiority, and P=0.053 for superiority). SAPPHIRE validates the use of carotid artery stenting instead of carotid endarterectomy in patients who have significant carotid artery disease but are at increased risk for carotid endarterectomy surgery.

CREST⁸ was a prospective, randomized, parallel, two-arm, multi-center clinical trial with blinded endpoint evaluation involving 2522 patients. The inclusion criteria included patients who have experienced a transient ischemic attack, amaurosis fugax, or non-disabling stroke within the past 180 days, and who have an ipsilateral carotid stenosis >=50% by angiography or >=70% by ultrasound or >= 70% by CTA or MRA are eligible for this study. Asymptomatic patients who have carotid stenosis >=60% by angiography or >=70% by ultrasound or >= 80% by CTA or MRA were eligible for this study. (Subjects with symptoms beyond 180 days are considered asymptomatic). Eligible patients were randomized to undergo either carotid artery stenting or carotid artery endarterectomy. All patients received aspirin antiplatelet therapy, treatment for hypertension, and management of other stroke risk factors. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization. For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). An interesting observation in the CREST trial is that younger patients actually did best with carotid artery stenting. CREST validates the expanded role of carotid artery stenting as an option to carotid endarterectomy in both symptomatic and asymptomatic patients with carotid artery disease who are not necessarily considered high risk for carotid surgery. Younger patients under the age of 70 may actually fare better with carotid artery stenting.

INTRODUCTION TO THE CAROTID ARTERY STENTING TECHNIQUE

Physicians at the Oklahoma Heart Institute have many years of experience with the technique of carotid artery stenting. By participating in some of the early multicenter registries studying the role of carotid artery stenting in both symptomatic and asymptomatic patients considered high risk for carotid endarterectomy, Oklahoma Heart Institute has contributed to the scientific body of knowledge that exists in this rapidly advancing field of medicine.

The carotid artery stent procedure requires that a small tube be placed in the femoral artery. The size of the tube is the same as the tube that is used during most cardiac catheterizations. Using x-ray guidance the tube is carefully advanced up through the aorta into the carotid artery of interest. Angiograms are performed by injecting contrast dye through the tube to quantitate the degree of narrowing in the carotid artery. After performing the angiogram, a thin wire is carefully advanced through the blockage in the carotid artery and ultimately placed several centimeters above the blockage. The wire is used a railroad track to take different pieces of equipment in and out of the vessel. Next, a small filter can be deployed past the blockage near the tip of the wire. This filter is called a distal protection device. It is designed to catch any plaque that might break off from the blockage before it travels up to the brain and causes a stroke. After deploying the distal protection device, a balloon tipped catheter is advanced over the wire and inflated to stretch open the blockage in the carotid artery. Then, a mesh tube called a stent is deployed across the blockage to create a scaffold which helps to keep the carotid artery open. After deploying the stent it is usually fully expanded by inflating a balloon inside of it again. Final angiograms are performed after the distal protection device and the wire are retrieved. The video link above demonstrates a carotid stent procedure performed by Dr. Raj Chandwaney.

SUMMARY OF THE NEW GUIDELINE RECOMMENDATIONS

Based on the compiled scientific evidence the following recommendations for selection of patients for carotid revascularization have been proposed in the 2011 update on the management of patients with extracranial carotid artery disease.¹ Like other published guidelines, the document states Class I recommendations should be performed, Class IIA recommendations are reasonable to perform, Class IIB recommendations may be reasonable to perform, and Class III recommendations are not beneficial and potentially harmful. The new guidelines for carotid artery revascularization are summarized below and shown in Table 1.

• Class I

– Symptomatic patients should undergo carotid endarterectomy (CEA) if they are documented to have significant ipsilateral internal carotid artery stenosis (70% by doppler, 50% by angiography) and the anticipated rate of perioperative stroke or mortality is less than 6%.

– Carotid artery stenting (CAS) is indicated as an alternative to CEA for symptomatic patients with significant ipsilateral internal carotid artery stenosis and the anticipated rate of periprocedural stroke or mortality is less than 6%.

• Class IIa

– It is reasonable to perform CEA in asymptomatic patients who have more than 70% stenosis of the internal carotid artery if the risk of perioperative stroke, MI, and death is low.

– It is reasonable to choose CEA over CAS when revascularization is indicated in older patients, particularly when arterial pathoanatomy is unfavorable for endovascular intervention.

– It is reasonable to choose CAS over CEA when revascularization is indicated in patients with neck anatomy unfavorable for arterial surgery.

• Class IIb

– Prophylactic CAS may be considered in selected patients with significant asymptomatic carotid artery stenosis.

– In symptomatic or asymptomatic patients at high risk of complications for carotid revascularization by either CEA or CAS because of comorbidities, the effectiveness of revascularization versus medical therapy alone is not well established.

• Class III (No Benefit)

– Carotid revascularization by either CEA or CAS is not recommended when atherosclerosis narrows the lumen by less than 50%.

– Carotid revascularization is not recommended for patients with chronic total occlusions of the targeted carotid artery.

– Carotid revascularization is not recommended for patients with severe disability caused by cerebral infarction that precludes preservation of useful function.

CONCLUSIONS

Stroke is an important cause of morbidity and mortality. Carotid artery disease is a common cause of ischemic stroke. Carotid endarterectomy surgery has been scientifically proven to reduce the risk of stroke in both symptomatic and asymptomatic patients with significant carotid artery disease. Additionally, years of real-world experience with carotid endarterectomy surgery have established carotid artery revascularization as the standard of care to be offered to patients with significant carotid artery stenosis. More recent studies confirm that carotid artery stenting is a viable less invasive option to be considered as an alternative to carotid endarterectomy surgery. The recently published 2011 guidelines on the management of patients with extracranial carotid artery disease support broadening the use of carotid artery stenting to treat patients with carotid artery disease and reduce their risk of stroke.

The reader should be advised that at the time of this publication, Medicare still limits payment for carotid artery stenting only for patients who have symptomatic carotid artery disease and are declared to be high risk for carotid endarterectomy surgery. This limitation in coverage exists despite the fact that the FDA has approved carotid artery stenting for symptomatic and asymptomatic patients who are at low risk for carotid endarterectomy surgery. Representatives from many of the professional societies that have endorsed the 2011 guideline update are actively engaging in dialogues with representatives from Medicare advising them to expand the coverage for carotid artery stenting. Many experts in the field (including this author) are concerned that Medicare’s slow response to expand coverage for carotid artery stenting is driven more by the current pressures to contain costs rather than weighing the merits of this innovative medical technology. Fortunately, medical directors at many private insurance companies are quickly responding to this evolving area of medicine by expanding the coverage for carotid artery stenting to a broader patient population. The physicians at Oklahoma Heart Institute will continue to closely follow this exciting area of medicine so we may offer our patients the most progressive treatment options available.

REFERENCES

1. Circulation, May 2011; doi:10.1161/CIR.0b013e31820d8c98

2. Heart Disease and Stroke Statistics Update. Circulation 2010; 121: e21-e170.

3. Stroke. 2001;32:2559-2566.

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5. JAMA 1995 May 10; 273(18):1421-8.

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7. New England Journal of Medicine. 2004; 351:1493-1501.

8. New England Journal of Medicine. 2010 Jul 1;363(1):11-23.