CAROTID ENDARTERECTOMY

Stroke is a major public health burden worldwide. It is the third leading cause of death and the leading cause of serious, long-term disability in the United States.^[528] Stroke is also a major contributor to health care costs. The direct and indirect costs of stroke in the United States in 2003 are estimated at $51.2 billion.^[528] Almost 700,000 people experience a new (approximately 500,000) or recurrent (approximately 200,000) stroke each year in the United States.^[528] Annually, there are more than 950,000 hospitalizations and 165,000 deaths caused by stroke.^[528] Approximately 83% of strokes are ischemic (i.e., cerebral thrombosis or embolism) in nature, and 7.6% of ischemic strokes result in death within 30 days of presentation.^[529]

Although treatment options to reverse the effect of acute ischemic stroke are limited, outcomes may be improved with appropriate therapy.^[530] The only approved therapy is intravenous tissue plasminogen activator (tPA).^[531] The American Heart Association/American Stroke Association published revised guidelines for the early management of patients with ischemic stroke.^[532] There are well-defined risk factors for patients with stroke, the most important of which is hypertension. Despite a well-documented decline in stroke mortality, the annual incidence rate of stroke may be increasing.^[533] This increase probably results from the growth in high-risk populations. If recent trends continue, increases in stroke deaths will outpace overall population growth, with a doubling in deaths over the next 30 years.^[534]

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The strong association between stroke and carotid artery occlusive disease is well known. The principal cause of occlusive disease is atherosclerosis, which most commonly involves the bifurcation of the common carotid artery, with frequent extension into the internal and the external carotid arteries.^[535] Cerebrovascular sequelae of carotid atherosclerosis may result from embolization of thrombus or atheromatous debris or from a reduction in flow (i.e., hypoperfusion) secondary to stenosis. The latter probably accounts for less than 10% of the cerebrovascular sequelae of carotid atherosclerosis.^[536] Although much is known about the genesis and evolution of atherosclerosis, significantly less is known about the circumstances that lead to plaque instability and rupture. Regardless of the mechanism, the degree of cerebral injury depends on such factors as plaque morphology, characteristics of the embolus, duration of hypoperfusion, cerebrovascular vasoreactivity, integrity of the circle of Willis, and cerebral collateral circulation. Clinical manifestations of carotid disease represent a spectrum of conditions, with fatal or debilitating stroke secondary to cerebral infarction at one end of the spectrum, ranging successively through nondebilitating stroke, transient ischemic attack, and amaurosis fugax (i.e., transient attack of monocular blindness) to an asymptomatic bruit. The incidence of perioperative stroke in unselected patients,^[537] patients with asymptomatic carotid bruit,^[538] and patients with at least 50% carotid stenosis^[539] undergoing general anesthesia and surgery is approximately 0.1%, 1.0%, and 3.6%, respectively.

Indications

Endarterectomy of the carotid bifurcation has been used to reduce symptoms and prevent stroke for more than 40 years. The efficacy of carotid endarterectomy for prevention of ipsilateral stroke in patients with and without symptoms has been demonstrated in randomized clinical trials.^{[540] [541]} In centers of excellence, it is a low-risk procedure with excellent long-term durability.^[542] The first successful carotid endarterectomy was performed by DeBakey in 1953 and later reported with a 19-year follow-up.^[543] Carotid endarterectomy is the most common peripheral vascular surgical procedure performed in the United States, with an estimated 130,000 procedures performed annually.^[544] The American Heart Association^[545] and others ^[546] have published guidelines for carotid endarterectomy. The rate and number of carotid endarterectomies have fluctuated significantly since the early 1970s. With marked growth in the specialty of vascular surgery and an expanding list of surgical indications, the number of carotid endarterectomies performed in nonfederal hospitals increased from 15,000 in 1971 to 107,000 in 1985^[547] but then declined substantially over the next 5 to 6 years.^[548] The decline probably resulted from publications questioning the indications for the procedures and isolated reports citing excessively high rates of operative morbidity and mortality.^{[549] [550]}

In 1992, a marked increase in the number of carotid endarterectomies occurred after the results of two large-scale, prospective, randomized trials were published.^[548] The North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial reported definitive results for symptomatic patients with high-grade carotid stenosis (70–99%). ^{[540] [551]} In the North American Symptomatic Carotid Endarterectomy Trial, at 2 years' follow-up the stroke rate for surgical patients was 9%, compared with 26% for medical patients. ^[540] This benefit of carotid endarterectomy has persisted at 8 years of follow-up.^[552] In the European Carotid Surgery Trial, the long-term stroke rate was 2.8% for surgical patients, excluding a perioperative stroke and death rate of 7.5%, and 16.8% for medically managed patients.^[551]

The efficacy of carotid endarterectomy in asymptomatic patients with carotid stenosis has been evaluated in four randomized trials.^{[541] [553] [554] [555]} A fifth, the European Asymptomatic Carotid Surgery Trial, is ongoing and expected to conclude recruitment of its 3200 patients in 2004.^[556] The Carotid Artery Surgery Asymptomatic Narrowing Operation Versus Aspirin trial, the first to publish its results, concluded that carotid endarterectomy was not indicated for asymptomatic patients with 50% to 90% carotid stenosis.^[553] Unfortunately, this study was seriously flawed and the results questioned. The Mayo Asymptomatic Carotid Endarterectomy trial was terminated early because of a significantly increased number of MIs and transient cerebral ischemic events in the surgical group.^[554] Most of these events were not related to surgery itself but rather to the absence of aspirin in the surgical group. The Department of Veterans Affairs trial was designed to compare the effects of carotid endarterectomy plus aspirin with medical treatment (i.e., aspirin) in asymptomatic male patients with 50% or greater carotid stenosis.^[555] This trial demonstrated a significant reduction in ipsilateral neurologic events in the surgical group (8%) compared with the medical group (20.6%). However, the combined incidence of stroke and death was not different between study groups. The Asymptomatic Carotid Atherosclerosis Study, the largest of the completed trials, demonstrated that patients with asymptomatic carotid stenosis (≥60%) who were treated with carotid endarterectomy and aspirin have a reduced 5-year risk of ipsilateral stroke compared with patients treated with aspirin alone (5.1% versus 11.0%).^[541] These results reflect only a 5.9% absolute risk reduction in 5 years, which is just above 1% per year. Improvement in outcome for patients randomized to endarterectomy in this trial did not reach significance until 3 years after surgery.

Although the North American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid Artery Study have clearly defined those individuals who are likely to benefit from carotid endarterectomy, it has been suggested that the significant increase in the number of carotid endarterectomies performed over the past decade may be caused in part by the extrapolation of trial results to patients and settings not directly supported by the trials.^{[544] [557]} For example, both trials restricted enrollment to patients younger than 80 years, and both trials carefully selected institutions and surgeons to optimize the results of surgery. The Asymptomatic Carotid Artery Study, in subgroup analysis, could not demonstrate a significant benefit for women. ^[541] With the advent of a second interventional treatment modality, percutaneous

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