Management of Carotid Artery Disease

Endarterectomy Versus Stenting

Carol Mackenzie Jackson, PhD, PA-C

Carotid artery stenosis (CAS) may cause 20% of ischemic strokes. Which patients are at risk, which should be screened—and what treatment option is most suitable for your patient with CAS?

Carotid artery disease is a treatable cause of ischemic stroke, a potentially devastating event that affects approximately 700,000 Americans each year and results in more than 160,000 deaths.^1,2 Stroke-related medical costs, including associated disability, now approach $60 billion per year. Despite advances in treatment, stroke remains the third leading cause of death in the United States.³

As the population ages, stroke prevention has become an increasing challenge for primary care providers. Guiding patients at risk toward the appropriate testing and treatment can offer lifelong benefits. This article will summarize current practice recommendations for screening asymptomatic individuals and for treatment of carotid artery disease using carotid endarterectomy or carotid angioplasty with stenting.

Scope and Screening
Carotid artery stenosis (CAS) is defined as atherosclerotic narrowing of the extracranial carotid arteries. Possibly 20% of ischemic strokes (which represent more than 85% of all strokes) result from CAS, a condition that may or may not be symptomatic.⁴ Symptomatic CAS may be represented by a cerebrovascular accident, a transient ischemic attack, or one of an array of more subtle but enduring neurologic deficits.

The prime risk factor for CAS is prior history of cerebrovascular disease.⁴ Cardiovascular disease or cigarette smoking doubles a patient’s risk for developing CAS. Other risk factors include age greater than 65, male gender, hypertension, atrial fibrillation, and clotting disorders.

Population studies based on carotid ultrasonography estimate the prevalence of CAS at 0.5% to 8.0% in the general population.^4-6 Clinically significant CAS (60% or higher) has been estimated at 1% in those older than 65.⁴

The degree of carotid occlusion correlates directly with the risk of ipsilateral stroke. The rate of stroke among asymptomatic patients with CAS of at least 80% is 3.5% to 5.0% per year.⁷ To date, there is no clinically useful risk model to identify those who have CAS or will develop it.

Screening the general population for asymptomatic CAS is not currently recommended.^4,8 Guidelines published in 2007 by the Society for Vascular Surgery (SVS)³ advise ultrasound screening only for persons 55 and older who have cardiovascular risk factors, including diabetes, hypertension, hypercholesterolemia, a history of smoking, or known cerebrovascular disease. That same year, the American Society of Neuroimaging⁹ recommended screening of adults 65 or older who have three or more cardiovascular risk factors.

Ultrasound screening is approximately 94% sensitive and 92% specific for moderate to severe CAS (ie, 60% to 90% occlusion).⁴ Patients with positive ultrasound findings may next undergo computerized axial angiography, magnetic resonance angiography, or digital subtraction angiography.

Angiography can detect with good precision the degree and location of carotid occlusion, which in turn helps to select treatment options, in consideration of their inherent risks and benefits. These options are medical therapy alone, or medical therapy combined with carotid endarterectomy (CEA), or carotid angioplasty with stenting.

The Research
Stroke prevention, long since a medical priority, is most commonly sought by way of pharmacotherapy combined with lifestyle modification. Surgery, in the form of CEA, also plays an enduring and proven role. Randomized trials, including three landmark studies,^10-12 have established CEA as standard treatment for symptomatic and high-grade occlusive carotid disease. The North American Symptomatic Carotid Endarterectomy Trial (NASCET)¹⁰ and the European Carotid Surgery Trial (ECST)¹¹ provided the basis for stratifying symptomatic patients and determining whether surgery will produce a reasonable benefit. The Asymptomatic Carotid Atherosclerosis Study (ACAS)¹² extended the research to asymptomatic patients with high-grade stenosis.^8,13 The benefits of CEA for elderly patients (75 and older) with significant comorbidities were supported in the 2009 New York Carotid Artery Surgery Study (NYCAS).¹⁴

Researchers for ACAS,¹² which compared medical therapy alone with CEA plus medical therapy in asymptomatic patients with CAS, reported a relative risk (RR) reduction of 0.53 in patients undergoing CEA, with a 5.1% five-year rate of stroke or death in the CEA group versus 11.0% among patients receiving medical therapy alone. The Asymptomatic Carotid Surgery Trial¹⁵ (ACST) yielded similar event rates (CEA, 6.4%; medical therapy alone, 11.8%). In both trials, the perioperative (30-day) risk of stroke or death associated with CEA ranged from 2.7% to 3.1%. In the long term (five to 10 years and beyond), RR reduction remains uncertain.

However, CEA remains the gold standard for the treatment of severe carotid artery disease. Currently, about 75% of patients who undergo CEA for significant CAS are asymptomatic.¹³

Complications associated with CEA occur at an ascending rate, commensurate with the patient’s preoperative stroke history. Researchers for the NYCAS¹⁴ reported a 30-day post-CEA rate of stroke or death of nearly 3% among asymptomatic patients with no history of stroke or TIA; nearly 8% among patients with previous stroke; and more than 13% in patients with crescendo TIA or evolving stroke. A significant increase in complications (including stroke or death) was reported among patients with coronary artery disease or with diabetes requiring insulin therapy.

The Case for Carotid Angioplasty with Stenting
Though broadly accepted and practiced, CEA carries significant risk for symptomatic patients and for those who face higher surgical risks, such as diabetes or cardiovascular disease, or anatomic issues such as contralateral occlusions (see Table 1).

Carotid angioplasty with stenting emerged in the 1990s as a less invasive alternative to CEA that could be performed under local anesthesia and with little or no sedation. In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS),¹⁷ no significant difference was found in three-year stroke risk between patients assigned randomly to CEA or to carotid stenting.

The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial,^7,16,18 an industry-sponsored study, was the first multicenter study to compare CEA with stenting in patients considered at high surgical risk. All stenting procedures were performed using an intraoperative embolic protection device. Patients with stents had a 4.8% risk of stroke, MI, or death in the 30-day postoperative period, compared with 9.8% among patients who underwent CEA. Despite their potential clinical relevance, these results were not found to be statistically significant.

The risk of ipsilateral stroke at one year was similar between treatment groups. Follow-up data published in 2008 and 2009 showed comparable outcomes and no differences in repeat revascularization rates between CEA and stent groups.^7,16 SAPPHIRE is now conducting a worldwide registry study in an effort to extend its results to a broader population. The Center for Medicare Services has approved carotid artery stenting with embolic protection for patients who meet the SAPPHIRE high-risk criteria.

Research on the effectiveness of distal protection devices in preventing intraoperative stroke is ongoing.¹⁹ In the interim, the SVS recommends embolic protection during all carotid stenting procedures.¹³ Perioperative medical management remains critical to the success of carotid stenting. This includes intraoperative heparin and clopidogrel for at least two to four weeks postoperatively.^7,16

In elderly patients (80 and older), carotid artery stenting may present a particularly high risk.^20,21 Investigators for the ongoing Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) have found a periprocedural risk of death or stroke at 12.1% among older CAS patients, compared with 4.0% among their younger counterparts.^21,22 This discrepancy has been attributed to age-related changes in vasculature that create a more hostile environment for endovascular devices.

Patients younger than 80 with significant but asymptomatic unilateral stenosis who are at average surgical risk are presently the focus of other trials. Now under way, the Carotid Angioplasty and Stenting versus Endarterectomy in Asymptomatic Subjects with Significant Extracranial Carotid Occlusive Disease Trial (ACT I) is the first major trial involving asymptomatic patients, and so far has shown a lower postintervention event rate than reported in smaller previous studies.²³ However, these patients are less likely to experience postoperative events than their symptomatic counterparts. Thus, the role of stenting in asymptomatic patients will require long-term follow-up.

To date, CEA retains its gold standard status as the optimum surgical treatment for preventing stroke-associated morbidity and mortality. At the same time, carotid stenting is emerging as an effective and less invasive alternative, especially for patients younger than 80 who are at high perioperative risk for CEA.

Treatment Guidelines
In 2008, the SVS¹³ issued clinical practice guidelines based on an empirical analysis of the currently available research on carotid stenosis. These guidelines address both medical and anatomic risk and acknowledge the limitations of comparing massive data obtained from robust but independent clinical trials. The SVS authors acknowledge that some terms (eg, high perioperative risk) remain somewhat difficult to define and are subject to practitioners’ interpretation.

In an effort to achieve consensus, the SVS investigators employed the British-based GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system²⁴ to stratify the strength of its recommendations. This system takes into account factors other than the quality of the data, including the reviewers’ values and preferences, and their evaluation of the data as presented (see Table 2¹³).

As the SVS authors note, there is no significant difference to date between outcomes for stenting versus CEA, including death or stroke within 30 days postprocedure and the need for revascularization within three years.¹³ They conclude, nevertheless, that CEA remains the treatment of choice for asymptomatic patients with moderate to severe stenosis. Symptomatic patients can be stratified based on age and medical and surgical risk when a choice is being made between CEA and stenting. In patients at high risk, lifelong pharmacologic therapy may be safer than either surgical or endovascular treatment.

The Role of Medical Management
Whether or not CEA or stenting is performed, medical therapy plays a crucial role in the management of carotid artery disease. Most patients are placed on aspirin therapy indefinitely unless its use is contraindicated (eg, by risk for gastrointestinal bleeding). The SVS practice guidelines¹³ incorporate medical therapy, citing joint recommendations issued in 2006 by the American Heart Association and the American Stroke Association (AHA/ASA)^1,25 for tight control of hypertension, blood glucose, and elevated cholesterol.

The AHA/ASA researchers also recommend antiplatelet agents (aspirin, clopidogrel, and/or dipyridamole) for patients with a history of TIA or noncardioembolic ischemic stroke. The guidelines advise moderate alcohol consumption, weight reduction for obese patients, and increased physical activity. Smoking cessation remains the sine qua non of vascular disease management.^1,25

Conclusion
Primary care providers play a pivotal role in identifying patients at risk for carotid artery disease and educating them about current treatment options. They have an opportunity to take a proactive role in screening patients (age 55 and over) who smoke or who have diabetes, high blood pressure, high cholesterol, or coronary artery disease.

Detection of moderate to severe CAS can lead to timely surgical intervention in asymptomatic individuals who may not realize they are at risk. Attentive medical and lifestyle management enhances the treatment of carotid disease and reduces the risk of stroke, its most devastating consequence.

References
1. Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37(6):1583–1633.

2. American Heart Association. Heart Disease and Stroke Statistics—2004 Update. www.americanheart.org/downloadable/heart/1079736729696HDSStats2004UpdateREV3-19-04.pdf. Accessed December 28, 2009.

3. Society for Vascular Surgery. SVS position statement on vascular screenings. www.vascularweb.org/patients/screenings/SVS_Position_Statement_on_Vascular_Screenings.html. Accessed December 28, 2009.

4. Wolff T, Guirguis-Blake J, Miller T, et al. Screening for carotid artery stenosis: an update of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2007;147(12):860- 870.

5. Colgan MP, Strode GR, Sommer JD, et al. Prevalence of asymptomatic carotid disease: results of duplex scanning in 348 unselected volunteers. J Vasc Surg. 1988;8(6):674-678.

6. Pujia A, Rubba P, Spencer MP. Prevalence of extracranial carotid artery disease detectable by echo-Doppler in an elderly population. Stroke. 1992;23(6):818-822.

7. Gurm HS, Yadav JS, Fayad P, et al; SAPPHIRE Investigators. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med. 2008;358(15):1572-1579.

8. US Preventive Services Task Force. Screening for carotid artery stenosis: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2007;147(12):854-859.

9. Qureshi AI, Alexandrov AV, Tegeler CH, et al. Guidelines for screening of extracranial carotid artery disease: a statement for healthcare professionals from the multidisciplinary practice guidelines committee of the American Society of Neuroimaging; cosponsored by the Society of Vascular and Interventional Neurology. J Neuroimaging. 2007;17(1):19-47.

10. Ferguson GG, Eliasziw M, Barr HWK, et al. The North American Symptomatic Carotid Endarterectomy Trial. Stroke. 1999;30(9):1751-1758.

11. Rothwell PM, Gutnikov SA, Warlow CP; European Carotid Surgery Trial. Reanalysis of the final results of the European Carotid Surgery Trial. Stroke. 2003;34(2):514-23.

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

13. Hobson RW 2nd, Mackey WC, Ascher E, et al; Society for Vascular Surgery. Management of atherosclerotic carotid artery disease: clinical practice guidelines of the Society for Vascular Surgery. J Vasc Surg. 2008;48(2):480-486.

14. Halm EA, Tuhrim S, Wang JJ, et al. Risk factors for perioperative death and stroke after carotid endarterectomy: results of the New York Carotid Artery Surgery Study. Stroke. 2009;40(1):221-229.

15. Halliday A, Mansfield A, Marro J, et al; MRC Asymptomatic Carotid Surgery Trial (ACST). Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363(9420):1491-1502.

16. Yadav JS, Wholey MH, Kuntz RE, et al; Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy Investigators (SAPPHIRE). Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med. 2004;351(15):1493-1501.

17. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet. 2001;357: 1729–1737.

18. Massop D, Dave R, Metzger C, et al. Stenting and angioplasty with protection in patients at high-risk for endarterectomy: SAPPHIRE Worldwide Registry first 2,001 patients. Catheter Cardiovasc Interv. 2009;73(2):129-136.

19. Barbato JE, Dillavou E, Horowitz MB, et al. A randomized trial of carotid artery stenting with and without cerebral protection. J Vasc Surg. 2008;47(4):760-765.

20. Suliman A, Greenberg J, Chandra A, et al. Carotid endarterectomy as the criterion standard in high-risk elderly patients. Arch Surg. 2008; 143(8):736-742.

21. Hobson RW 2nd, Howard VJ, Roubin GS, et al. Carotid artery stenting is associated with increased complications in octogenarians: 30-day stroke and death rates in the CREST lead-in phase. J Vasc Surg. 2004;40(6):1106-1111.

22. Lal BK, Brott TG. The Carotid Revascularization Endarterectomy vs. Stenting Trial completes randomization: lessons learned and anticipated results. J Vasc Surg. 2009;50(5):1224-1231.

23. Derdeyn CP. Carotid stenting for asymptomatic carotid stenosis: trial it. Stroke. 2007;38(2 suppl):715-720.

24. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926.

25. Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37(2):577-617.