Carotid Artery Disease

From Carotid Artery Disease: Diagnosis and Management for the Prevention of Stroke,Thirteenth Annual Max R. Gaspar Vascular Disease Symposium, sponsored by Keck School of Medicine,University of Southern California, Los Angeles

Educational Objectives

The goal of this program is to improve management of symptomatic and asymptomatic carotid artery disease. After hear­ing and assimilating this program, the clinician will be better able to:

1.   Identify patients at highest risk for stroke due to a carotid artery lesion.

2.   Describe the evidence favoring early carotid endarterectomy (CEA) for patients with symptomatic carotid ar­tery disease.

3.   Discuss the basic principles of management of asymptomatic carotid artery disease.

4.   Explain how evidence from the North American Symptomatic Carotid Endarterectomy Trial and the Asymp­tomatic Carotid Atherosclerosis Study should influence the surgical management of patients with carotid ar­tery disease.

5.   List the major complications of CEA.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and the planning committee re­ported nothing to disclose.

Acknowledgements

Drs. Comerota and Lee were recorded at Carotid Artery Disease: Diagnosis and Management for the Prevention of Stroke, Thirteenth Annual Max R. Gaspar Vascular Disease Symposium, held September 24, 2009, in Los Angeles, CA, and spon­sored by the Keck School of Medicine at the University of Southern California. The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.

Current Management of Symptomatic and Asymptomatic Carotid Disease

Anthony J. Comerota, MD, Adjunct Professor of Surgery, University of Michigan School of Medicine, Ann Ar­bor, and Director, Jobst Vascular Center, Toledo Hospital, Toledo, OH

Purpose of carotid endarterectomy (CEA): to prevent stroke; patients at highest risk  —  individuals with symptom­atic lesions, especially if those have already caused stroke; shortly after first stroke or transient ischemic attack (TIA) time of greatest risk; asymptomatic carotid disease indicates reassessment of stroke risk; however, even if all patients with asymptomatic carotid stenosis of 60% to 99% identified and treated with CEA or angioplasty and stent, 97% of strokes would still occur; in large registries, eg, Oxford Vascular Study, presence of carotid dis­ease most important identifier of risk for stroke after cerebrovascular events; »70% of strokes occurred within 4 wk after initial symptomatic event (probably underestimates problem); 70% of strokes after symptomatic event occur within 14 days (80% of those strokes within 4 days); Randall et al  —  study of 49 patients with TIA or stroke; median time to CEA 63 days; 25% had interim ischemic complication, including 5 strokes in those who had previous stroke; rate of stroke recurrence 30% within 60 days

Why vascular surgeons delay intervention: fear of hemorrhagic conversion; fear that procedure may cause stroke; fears not supported by data (stroke rate after CEA very low; early CEA not associated with increased morbidity); delaying surgery may expose patients to unnecessary risk (no additional risk associated with early CEA)

Data from North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST): strokes prevented at 5 yr per 1000 CEAs  —  among patients with 50% to 99% symptomatic steno­sis, CEA within 2 wk prevents 185 strokes, while CEA after 4 wk prevents 55 strokes (effectiveness of CEA re­duced by 70%); among patients with 70% to 99% stenosis, CEA within 2 wk prevents 230 strokes for every 1,000 patients, while CEA after ³4 wk prevents 79 strokes (effectiveness of CEA reduced 65%-70%); findings similar among patients with 50% to 69% stenosis; pooled data show that waiting 6 wk rather than 2 wk results in “enormous loss of effectiveness”; no sign of additional hemorrhagic conversion associated with early CEA, com­pared to medically treated patients; in speaker’s opinion, “symptomatic carotid artery disease should be treated as a vascular emergency”

Treatment of symptomatic carotid disease at Jobst Vascular Center: goal to care for patients within 48 hr of pre­sentation; patients with nondisabling stroke or TIA undergo carotid duplex ultrasonography and diffusion-weighted magnetic resonance imaging (MRI); patients with >50% carotid stenosis and less than two-thirds infarct in region of middle cerebral artery referred for urgent CEA protocol; all patients with symptomatic carotid disease (eg, am­aurosis fugax, recent TIA or stroke) placed on low-dose aspirin and clopidogrel; also placed on atorvastatin (80 mg/day), glucose control, and blood pressure control; goal to operate within 48 hr

Management of asymptomatic carotid disease: principles  —any procedure offered should reduce risk for stroke more than best medical care; do not perform procedure if procedure-related risk for stroke or death no better than with best medical care; if procedural risk 2.3%, performing CEA on 1000 patients will prevent 59 ipsilateral strokes within 5 yr (based on medical risk patients faced 15 to 20 yr ago); if all asymptomatic (60%-99%) steno­ses with procedural risk of 2.3% identified and underwent CEA, fewer than 5% of all strokes would be prevented

Relationship of carotid stenosis to stroke in asymptomatic lesions: 2 large, randomized trials showed no relation­ship; also showed no benefit with CEA performed on asymptomatic lesions in women (unless procedure-related events excluded); trials included no definition of best medical care, did not describe pharmacotherapy, and did not define treatment targets; impossible to determine if patients received best medical care or even good medical care; inappropriate to compare procedures done today with medical treatment given 20 yr ago; result is current controversy over management of asymptomatic carotid artery disease ; 2004 analysis  —  actual rate of procedure-related strokes 3.8% (number of ipsilateral strokes prevented reduced to 44 in 1000 patients over 5 yr); cost to prevent 1 stroke $428,000, based on risk for stroke in patients receiving medical care 20 yr ago; current medical care includes aspirin, dual platelet inhibition, high-dose statins, angiotensin converting enzyme (ACE) inhibitors, and aggressive lifestyle modification

Data from Asymptomatic Carotid Surgery Trial (ACST): showed significant decrease in rate of ipsilateral strokes with improved medical therapy, including increased use of statins; most recent paper from ACST reported stroke rate of 3.6% amortized over 5 yr

Current best medical care: includes platelet inhibition, statins, ACE inhibitors, angiotensin receptor blockers (ARBs), glucose control, aggressive hypertension control, exercise, and smoking cessation; platelet inhibition with low-dose (75 mg-150 mg daily) aspirin alone associated with 32% reduction in risk for stroke in randomized trials; addition of dipyridamole significantly reduced risk further; aspirin plus clopidogrel associated with significantly greater reduction of stroke in high-risk populations, compared to aspirin alone; statins  —  associated with signifi­cant risk reduction in high-risk patients; at Jobst Vascular Center, every patient scheduled for vascular surgery placed on statin preoperatively and receives statin prescription upon discharge; blood pressure control  —  benefit “enormous”, especially if target systolic pressure <130 mm Hg (results in significant reduction of risk, compared to target systolic blood pressure <140 mm Hg)

Summary of data on stroke from ipsilateral carotid disease since 1985: “remarkable” decrease in risk with best medical care; in Second Manifestations of Arterial Disease (SMART; 2007) study, investigators followed 221 pa­tients with >50% stenosis for >5 yr; patients with carotid disease had significantly more cardiovascular events than those without carotid disease, but only patients with occluded carotid artery had higher stroke rate; stroke rate among patients with 50% to 99% stenosis equal to that of patients with no carotid disease; annual stroke risk among those with 50% to 99% carotid stenosis <1%; probably cannot improve with procedure

Implications: future trials of procedures for asymptomatic carotid disease must be compared to best medical ther­apy; in future, surgeons will probably select only high-risk asymptomatic patients, based on imaging studies, bio­markers, and plaque composition; transcranial Doppler ultrasonography will be used to identify patients with embolic signals (contralateral occlusions place patients at high risk)

Conclusions: consider patients with symptomatic carotid artery disease (history of recent stroke or TIA with less than two-thirds infarct on ipsilateral cerebral hemisphere) as urgent if not emergency cases; treat asymptomatic pa­tients with aggressive medical therapy; place all patients on maximal doses of statins (benefits, but not complica­tions, dose-related); be selective in choosing patients for CEA

Carotid Endarterectomy And Stroke Prevention

William M. Lee, MD, Assistant Professor of Surgery, Division of Vascular Surgery, Keck School of Medicine, University of Southern California, Los Angeles

Background: manifestation of pathology  —  anatomic (intimal dissection, kinks, coils, redundancies, or fibromuscu­lar dysplasia); neoplastic processes (carotid body tumor); inflammatory processes (primary vasculitis); aneurysmal disease (infectious or acquired)

Epidemiology of stroke: stroke third leading cause of death in United States; causes »750,000 deaths per year; hem­orrhagic factors (eg, ruptured aneurysm) contribute to 10% to 20% of strokes; cause never identified in some cases, but majority of stroke-related deaths due to ischemia; usually sudden, associated with thromboembolic disease

Development of thromboembolic disease: consists of lipid deposition, inflammation, formation of fibrous cap, and potential rupture; ruptured plaque or ulceration provides nidus for further lipid deposition (ongoing source of em­bolism)

Four questions to address in surgical disease management: whether patient needs surgery; timing of surgery (if needed); type of incision; most likely findings 

Patient presentation: astute primary care physician may detect asymptomatic carotid disease by hearing cervical bruit during routine examination and ordering imaging studies; most patients present to surgeons with symptoms (hemiparesis, aphasia, or amaurosis fugax); TIA  —neurologic deficit lasting <24 hr, or reversible ischemic neuro­logic deficit lasting from 24 hr to several days; stroke (cerebrovascular accident)  —  associated with permanent deficit, although some recovery may occur

Need for surgery: symptomatic patients - NASCET enrolled >2000 patients with symptomatic carotid artery dis­ease; all had some degree of neurologic deficit and established angiographically confirmed carotid stenosis; ran­domized to medical therapy or surgery and stratified by degree of stenosis; outcomes among patients with 70% to 99% stenosis significantly different from those with 50% to 69% or <50% stenosis; surgery associated with peri­operative stroke and mortality rate of 6.5%; compared to medical therapy, CEA conferred significant benefit in preventing strokes among patients with 50% to 99% stenosis; surgery also showed beneficial trend in patients with <50% stenosis, although difference not statistically significant; asymptomatic patients  —  Asymptomatic Carotid Atherosclerosis Study (ACAS) enrolled 1600 asymptomatic patients with no history of neurologic events; all had established carotid stenosis >60%; randomized to medical or surgical therapy; perioperative stroke and mortality rate 2.3%; among patients in medical treatment arm, projected 5-yr event rate »11%, com­pared to 5.1% among patients in surgical treatment arm (most patients in surgical arm experienced stroke or mor­tality within perioperative period; emphasizes need for excellent perioperative complication rate); CEA more beneficial for men than for women; for all patients, surgery associated with relative risk reduction of 53% for ip­silateral stroke (P=0.004); degree of benefit associated with longevity; among patients not undergoing surgery, longevity associated with increasing risk for neurologic event; absolute risk reduction in ACAS 1% per year; re­inforces need for good surgical outcomes; conclusions  —  NASCET suggests symptomatic patients with >50% ipsilateral carotid stenosis benefit from surgery; ACAS showed asymptomatic patients with >60% stenosis bene­fit; caveats  —  rate of perioperative complications must be low to see benefit from surgery; medical therapy in NASCET and ACAS consisted mostly of aspirin; advent of clopidogrel and statins may improve outcomes; pa­tients may now need more stenosis to show significant benefit from surgery; surgeons must also consider sex and longevity when selecting patients

Timing of surgery: elective for asymptomatic patients; urgent for stable symptomatic patient (risk increases with delay); hasty surgery on patient with history of recent stroke may produce bad outcomes; neurologic symptoms may worsen, possibly due to edema around infarcted or ischemic area; in handful of patients, ischemic stroke may convert to hemorrhagic stroke, with devastating complications; speaker recommends delaying surgery until neurologic symptoms reach plateau and patient stable

Choice of incision: oblique  —  performed just in front of sternocleidomastoid muscle; allows superior and inferior extension and provides wide field of view; transverse cervical collar  —performed over bifurcation; thought to have superior cosmetic results; other surgical considerations  —  routine or selective shunt; choice of anesthetic (local or general); whether to use patch; whether to perform eversion CEA

Most likely findings: atheromatous or atherosclerotic plaque that contributes to patient’s neurologic problems

Possible complications: vagus, hypoglossal, glossopharyngeal, and facial nerves most commonly injured during neck surgery; other injuries include bleeding or hematoma (in neck, large hematoma may compromise airway; sometimes life-threatening); systemic hypotension (may require admitting patient with vasopressor support); cerebral hypertension (may lead to seizures or hemorrhage, with potentially devastating outcomes); infection (may be difficult to control; infected patch or field may require reoperation and placement of vein patch)

Suggested Reading

Bond R et al: Time trends in the published risks of stroke and death due to endarterectomy for symptomatic carotid steno­sis. Cerebrovasc Dis 18:37, 2004; de Donato G et al: Long-term results of carotid artery stenting. J Vasc Surg 48:1431, 2008; Goessens BM et al: Asymptomatic carotid artery stenosis and the risk of new vascular events in patients with mani­fest arterial disease: the SMART study. Stroke 38:1470, 2007; Hallett JW Jr et al: Comparison of North American Symp­tomatic Carotid Endarterectomy Trial and population-based outcomes for carotid endarterectomy. J Vasc Surg 27:845 1998; Long GW et al: Contemporary outcomes for carotid endarterectomy at a large community-based academic health center. Ann Vasc Surg 21:321, 2007; Naylor AR et al: Who benefits most from intervention for asymptomatic carotid stenosis: pa­tients or professionals? Eur J Vasc Endovasc Surg 37:625, 2009; Naylor AR: Is surgery still generally the first choice inter­vention in patients with carotid artery disease? Surgeon 6:6, 2008; Naylor AR: Occam’s razor: Intervene early to prevent more strokes! J Vasc Surg 48:1053, 2008; Randall JK et al: Complications during the waiting period for carotid endarter­ectomy. Ann Vasc Surg 23:436, 2009; Rijbroek A et al: Asymptomatic carotid artery stenosis: past, present and future. How to improve patient selection? Eur Neurol 56:139, 2006; Rothwell PM et al: Population-based study of event-rate, in­cidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 366:1773, 2005; Sbarigia E et al: Early carotid endarterectomy after ischemic stroke: the results of a prospective multi­center Italian study. Eur J Vasc Endovasc Surg 32:229, 2006.