Vol. 17, Issue 4 Jul 2017

Case Management: Carotid Artery Stenosis

Contributing Author: Raghu Motaganahallli, MD, MS

ACCREDITATION STATEMENT
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Indiana University School of Medicine (IUSM) and IU Health Physicians. IUSM is accredited by the ACCME to provide continuing medical education for physicians.

DESIGNATION STATEMENT
IUSM designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

FACULTY DISCLOSURE STATEMENT
In accordance with the ACCME Standards for Commercial Support, educational programs sponsored by IUSM must demonstrate balance, independence, objectivity, and scientific rigor. All faculty, authors, editors, and planning committee members participating in an IUSM-sponsored activity are required to disclose any relevant financial interest or other relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services that are discussed in an educational activity.

Dr. Raghu Motaganahalli has disclosed that he received consulting fees for teaching from Silk Road Medical. Any potential conflict of interest has been resolved.

OBJECTIVES
After reading this article, the reader should be able to:
• Recognize the impact of carotid artery stenosis (CAS) as a cause of stroke and stroke-related deaths.
• Identify the common denominator linking carotid, coronary, and peripheral artery disease.
• Summarize the roles for medical therapy and revascularization in CAS. 
• Compare and contrast patient outcomes for carotid endarterectomy and carotid stenting.
• Discuss the potential for transcarotid stenting as another option for carotid artery revascularization.

Activity Launch Date: July 2017

Expiration Date: July 2018

COMMERCIAL SUPPORT
This CME activity does not have any commercial support.

A 70-year-old female presents at a local hospital with right upper extremity weakness and associated speech deficits. Computed tomography (CT) and magnetic resonance imaging (MRI) are performed and indicate a left frontotemporal infarct, and she is diagnosed with a left hemispheric stroke.

The patient is evaluated at Indiana University Health Methodist Hospital one week later. She reports living independently, stopping smoking 10 years ago (after a 30-pack year history), and undergoing radical neck dissection and neck irradiation for tonsillar cancer in 2005. Current medications are aspirin, clopidogrel, and atrovastatin. Physical examination demonstrates complete motor recovery but persistent dysarthria. Duplex ultrasonography* and CT angiography (CTA) of the neck show an approximately 80 percent stenosis of the left extracranial internal carotid artery (Figure 1 see page 2).


Overview of Carotid Artery Stenosis

Carotid artery stenosis (CAS), which most frequently occurs at the carotid bifurcation,2 is responsible for up to 20 percent of the nearly 800,000 strokes and 170,000 stroke-related deaths that occur annually in the United States.3 Reduction of blood flow caused by the build-up of atheromatous plaque results in symptoms referable to brain regions at the border zones between the anterior, middle, and posterior cerebral arteries, where perfusion pressure is the lowest and most vulnerable to further reduction by proximal stenosis.4 Such lesions often cause transient ischemic attacks (TIAs), which are characterized by weakness of the upper or lower extremities, hemiplegia, difficulty speaking, and/or vision deficits (amarosis fugax).

“The prevalence of carotid artery disease increases with age, and prognosis is most closely linked to the degree of stenosis and symptoms,” explains Raghu Motaganahalli, MD, associate professor of surgery at Indiana University School of Medicine and vascular surgeon at IU Health. “A 2.0 mm residual luminal diameter or a 60 to 70 percent reduction in diameter is linked to a marked increased risk for ischemic stroke.”5,

Because atherosclerosis is the common denominator for carotid, coronary, and peripheral artery disease, two or all three conditions commonly coexist. Thus, Dr. Motaganahalli recommends a comprehensive vascular examination for every patient diagnosed with CAS.


CAS Evaluation and Management

In patients without symptoms, CAS is typically detected as a carotid bruit during routine physical examination. This nonspecific finding is present in 70 to 89 percent of individuals with a 2.0 mm luminal opening.2 CAS may also be diagnosed incidentally during screening ultrasonography performed to assess coronary artery or peripheral artery disease. Carotid duplex ultrasonography, CTA, and MRI angiography are widely used to evaluate the extent of CAS and guide clinical decision-making.

“Low-risk patients with asymptomatic carotid artery stenosis can usually be effectively managed with aggressive medical therapy, which includes adopting a healthy lifestyle, antiplatelet and statin therapy, and control of hypertension and diabetes (Table 1),” Dr. Motaganahalli says. “High-risk asymptomatic patients (stenosis >70 percent6-9)* and those with symptomatic disease, defined as focal neurologic symptoms of sudden onset and referable to the appropriate carotid artery distribution, require both medical management and carotid artery revascularization to reduce their risk for stroke.”6,10,11


“High-risk asymptomatic patients (stenosis ≥70 percent) and those with symptomatic disease, defined as focal neurologic symptoms of sudden onset and referable to the appropriate carotid artery distribution, require both medical management and carotid artery revascularization to reduce their risk for stroke.”

Carotid Artery Revascularization

Two options are available for revascularizing the carotid artery: carotid endarterectomy (CEA) and carotid artery stenting.

Carotid Endarterectomy

In the United States, CEA remains the primary revascularization procedure for CAS.12 Randomized controlled trials have established the safety and effectiveness of CEA in reducing ipsilateral stroke risk,6,10,11 and it is the preferred intervention for: 1) symptomatic disease; 2) patients with a heavy thrombus burden, heavily calcified lesions, and/or a hostile aortic arch; and 3) persons older than 80 years. A meta-analysis of the major CEA trials found the greatest benefit was obtained when patients underwent the procedure within two weeks after a TIA or stroke.<13

CEA is performed under local/regional or general anesthesia through a neck incision bordering the sternocleidomastoid muscle or at the level of the carotid bulb. The carotid artery is repaired primarily or patched using a saphenous vein or synthetic or animal-derived material (e.g., Dacron, polytetrafluoroethylene, bovine pericardium). Patients are generally hospitalized one day, during which time their neurologic status and blood pressure are carefully monitored. Perioperative complications include stroke; MI; hyperperfusion syndrome; cranial nerve injury; parotitis; and bleeding, which can result in neck hematoma and require reoperation. When CEA is performed at high-volume tertiary care centers, perioperative mortality ranges from <0.5 to 3.0 percent.



Carotid Artery Stenting

Transfemoral stenting. Carotid artery stenting was developed in the 1990s as an alternative to CEA, particularly for patients at high risk for surgical complications. The procedure is traditionally performed via a transfemoral percutaneous approach and involves balloon angioplasty and placement of a bare metal stent. Drug-eluting stents, widely used for coronary artery disease, are rarely used in this setting because of the larger diameter of the carotid arteries and the low rate of restenosis. A neuroprotective device, either filter or flow reversal, is inserted before stent deployment to collect dislodged embolic debris and prevent antegrade dissemination to the brain during revascularization.

Multiple randomized clinical trials have shown equivalent ipsilateral stroke prevention with CEA and carotid artery stenting.3,14-16 Moreover, 10-year follow-up of 2,502 patients enrolled in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) found no significant difference between the two procedures with respect to the risk for periprocedural stroke, MI, or death.16 A meta-analysis of five clinical trials involving 6,526 patients found that while long-term overall stroke risk was significantly higher with carotid artery stenting, this was mostly attributable to periprocedural minor (non-disabling) stroke. Conversely, stenting was associated with lower periprocedural rates of MI and cranial nerve palsy.17

Transcarotid stenting. Transcervical carotid artery revascularization (TCAR) (Figure 2) is the most recent option for transcarotid stenting. The procedure, performed under general or local anesthesia, employs direct carotid access for less invasive stent delivery and lower risk for cranial nerve injury. An external filter circuit is used to capture embolic debris and create an arteriovenous shunt for flow reversal (Figure 3).

“The ROADSTER multicenter trial evaluated transcarotid stenting with dynamic flow reversal in 208 symptomatic (>50 percent stenosis) and asymptomatic patients (>70 percent stenosis),”12 Dr. Motaganahalli describes. “The per protocol overall stroke rate was 0.7 percent in patients at high surgical risk—the lowest reported to date for any clinical trial of carotid artery stenting and comparable to the carotid endarterectomy limb of CREST in standard-risk patients.”

IU Health is one of only two centers in Indiana that offers TCAR. To date, vascular surgeons at IU Health Methodist Hospital have performed more than 100 such procedures, with results comparable to the ROADSTER trial.

Because of the patient’s history of neck surgery and irradiation, recent neurologic symptoms, and identification of high-grade internal carotid artery stenosis, she is offered and agrees to undergo TCAR with dynamic flow reversal. The procedure is performed under general anesthesia with intraoperative electroencephalographic monitoring. She is closely observed in the intensive care unit overnight and discharged the following day on a daily regimen of dual antiplatelet therapy (aspirin and clopidogrel) and atorvastatin.

At follow-ups one month and one year post-procedure, the patient reports no recurrent neurologic symptoms and complete recovery of motor function. Duplex ultrasonography demonstrates patency of the carotid stent. She will continue to be monitored long-term for stenosis recurrence at IU Health Methodist Hospital.

The ROADSTER 2 post-approval study of transcarotid artery revascularization in patients with significant CAS (NCT02536378)* is currently recruiting patients and expected to be completed by June 2018. IU Health is participating in this clinical trial, which has as its primary outcome measure the rate of procedural success during the first 30 days after stent placement.

“If the results from ROADSTER 2 are consistent with those from the first study, I believe transcarotid stenting will truly be a gamechanger for patients with carotid artery stenosis, supplanting endarterectomy as the standard of care within the next decade,” Dr. Motaganahalli predicts. “Currently, we offer all patients requiring revascularization of the carotid artery the option of transcarotid stenting unless the stenosis is located in the proximal carotid artery, the site of catheter insertion. This location is very uncommon, however, and we have encountered it in only one or two of our patients.

“At the present time, carotid endarterectomy and carotid artery stenting should be considered complementary therapies that are tailored to the patient based on his or her individual anatomic characteristics and preferences,” he concludes.

*Symptomatic: >50 percent stenosis; asymptomatic: >80 percent stenosis.
Dual Antiplatelet Therapy in Symptomatic Carotid Artery Stenosis

Although aspirin is a mainstay of antithrombotic therapy for the secondary prevention stroke, it prevents at best only 20 percent of recurrences.18 DAPT with aspirin and clopidogrel, a thienopyridine that inhibits ADPdependent platelet aggregation, is more effective than aspirin alone in decreasing stroke risk.19 A systematic review and meta-analysis of seven trials that collectively enrolled more than 13,200 patients with a history of TIA or stroke found low-dose aspirin (75-100 mg) plus clopidogrel (75 mg) decreased the relative risk of total stroke (TIA, ischemic stroke, or intracranial hemorrhage) by 24 percent. No additional benefit was obtained by substituting a more potent antiplatelet inhibitor (e.g., prasugrel, ticagrelor) for clopidogrel.

Because of the stroke-protective benefits of DAPT, Dr. Motaganahalli says patients undergoing carotid endarterectomy or carotid artery stenting at IU Health are maintained on aspirin and clopidogrel long-term, with treatment discontinued only if bleeding complications develop.

CME Credit Form

Raghu Motaganahallli, MD, MS

Vascular Surgeon, IU Health
Associate Professor of Surgery, Division of Vascular Surgery, and Program Directory for Residency and Fellowship Programs, IU School of Medicine
rmotagan@iuhealth.org

Dr. Motaganahalli received his medical degree from Bangalore University in India and completed a residency in surgery and a fellowship in vascular surgery at the St. Louis University Hospital in Missouri. His clinical interests focus on complex endovascular surgery; his research interests include the use of endovascular surgery for the treatment of CAS, aortic aneurysm, lower extremity ischemia, and vascular trauma and the use of thermotherapy for intermittent claudication.

A fellow of the American College of Surgeons and president-elect of the Indiana state chapter, Dr. Motaganahalli is a member of the Society for Vascular Surgery and the Vascular and Endovascular Surgery Society, among other professional organizations. He is an investigator for more than 20 drug or device multicenter clinical trials and is collaborating with other US university vascular surgery programs to establish a registry for the long-term follow-up of patients undergoing endovascular aneurysm repair.

Dr. Motaganahalli is the author of numerous peer-reviewed journal articles and textbook chapters and lectures extensively in the United States and internationally.


  1. Zwiebel WJ. Duplex sonography of the cerebral arteries: efficacy, limitations, and indications. AJR Am J Roentgenol. 1992;158(1):29-36.

    2. Grotta JC. Clinical practice. Carotid stenosis. N Engl J Med. 2013;369(12):1143-1150.

    3. Rosenfield K, Matsumura JS, Chaturvedi S, et al. Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis. N Engl J Med. 2016;374(11):1011-1020.

    4. Carpenter DA, Grubb RL, Jr., Powers WJ. Borderzone hemodynamics in cerebrovascular disease. Neurology. 1990;40(10):1587-1592.

    5. Brice JG, Dowsett DJ, Lowe RD. Haemodynamic Effects of Carotid Artery Stenosis. Br Med J. 1964;2(5421):1363-1366.

    6. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Enarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273(18):1421-1428.

    7. Halliday A, Harrison M, Hayter E, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010;376(9746):1074-1084.

    8. Hobson RW, 2nd, Weiss DG, Fields WS, et al. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group. N Engl J Med. 1993;328(4):221-227.

    9. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the 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 for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J A  Coll Cardiol. 2011;57(8):1002-1044.

    10. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325(7):445-453.

    11. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351(9113):1379-1387.

    12. Kwolek CJ, Jaff MR, Leal JI, et al. Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal. J Vasc Surg. 2015;62(5):1227-1234.

    13. Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ, Carotid Endarterectomy Trialists C. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004;363(9413):915-924.

    14. Eckstein HH, Ringleb P, Allenberg JR, et al. Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial. Lancet Neurol. 2008;7(10):893-902.

    15. Brott TG, Hobson RW, 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363(1):11-23.

    16. Brott TG, Howard G, Roubin GS, et al. Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis. N Engl J Med. 2016;374(11):1021-1031.

    17. Sardar P, Chatterjee S, Aronow HD, et al. Carotid Artery Stenting Versus Endarterectomy for Stroke Prevention: A Meta-Analysis of Clinical Trials. J Am Coll Cardiol. 2017;69(18):2266-2275.

    18. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324(7329):71-86.

    19. Gouya G, Arrich J, Wolzt M, et al. Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis. Stroke. 2014;45(2):492-503.

    20. Spence JD, Song H, Cheng G. Appropriate management of asymptomatic carotid stenosis. Stroke and Vascular Neurology. 2016;1(e000016):1-8.