In Western countries, stroke is the third leading cause of death, after heart disease and cancer, and is the most common cause of permanent disability.1 This neurological condition affects &0.2% of the population each year, and the incidence of stroke-related death is expected to double over the next 30 years. The estimated direct and indirect costs of stroke in the United States for the year 2006 are estimated to be $58 billion.1 A stenosis of the internal carotid artery may be responsible for 10% to 20% of all strokes or transient ischemic attacks. Carotid artery stenting (CAS) has emerged as a potential alternative revascularization strategy to carotid endarterectomy (CEA) for patients with carotid stenosis.
A 75-year-old man known to have an asymptomatic occlusion of the left internal carotid artery presented with transient left arm weakness. His cardiovascular risk factors included smoking and hyperlipidemia. Because of poor compliance, the patient was on no medication at the time of admission. Urgent computed tomography scan of the brain showed no bleeding or ischemic lesions. Same-day carotid Duplex ultrasound demonstrated a ≥70% stenosis of the right and the previously diagnosed chronic occlusion of the left internal carotid arteries. Aspirin and a statin were administered, and revascularization options were discussed with the patient.
Large-scale randomized clinical trials have established the superiority of CEA over medical management in preventing neurological events in patients with high-grade carotid stenosis. A pooled analysis of the randomized data showed that surgery was highly beneficial for individuals with symptomatic stenosis ≥70% and of some benefit for those with 50% to 69% stenosis.2 In asymptomatic patients, surgery has been associated with a small but definite reduction in the risk of stroke in the presence of a stenosis ≥60%.3 The American Heart Association guidelines support CEA for all symptomatic patients with ≥50% internal carotid artery stenosis and for asymptomatic patients with stenosis ≥60%, as long as the estimated perioperative death or stroke rate is <3% and life expectancy is ≥5 years.4 For individuals with surgical risk up to 5%, CEA is considered an acceptable but not proven therapy for stenosis ≥75%.
The excellent surgical outcomes achieved in randomized trials are frequently considered the benchmark for CAS. These results, however, were obtained by high-volume surgeons treating low-risk patients and may not be reproduced in clinical practice. Accordingly, an analysis on >110 000 Medicare beneficiaries showed that although within randomized trials, the perioperative mortality rate for CEA was as low as 0.6% for symptomatic and 0.1% for asymptomatic patients, the overall perioperative mortality rate in the hospitals participating in the trials was 1.4%.5 In addition, the study detected a perioperative mortality rate of 2.5% in low-volume hospitals. Although low operator and hospital volumes are factors that have been repeatedly associated with poor outcomes after CEA, most surgeries are performed in the United States by low-volume surgeons. An analysis that included >136 000 CEAs documented a mean volume per operator of 15 procedures per year, whereas one third of the patients were operated on by surgeons with a mean CEA volume of 5 per year.6 With respect to patient selection, the impact of comorbidities on the outcomes of CEA is recognized. High-risk features, according to the Centers for Medicare and Medicaid Services (CMS), are listed in Table 1, and the advantages and disadvantages of CEA are reported in Table 2.
Percutaneous carotid revascularization with balloon angioplasty was pioneered in the early 1980s. The advent of stent technology in the mid 1990s allowed protection against dissections and a restenosis rate in the single-digit range. Although prospective comparative studies are lacking, stenting has been virtually uniformly embraced as superior to angioplasty in this setting. The introduction of embolic protection devices (EPDs) in the year 2000 made CAS a safer procedure (Figure 1). The need for EPDs came from transcranial Doppler observations that embolization, although in most cases clinically silent, occurred in virtually all cases of both surgical and endovascular carotid revascularization. A broadly shared opinion, although not unanimous, supports the use of EPDs during CAS, despite the lack of randomized data. A systematic review of 2357 patients who underwent CAS without EPD and 839 protected procedures documented 30-day death and stroke rates of 5.5% and 1.8% (P<0.001), respectively.7 Similarly, in a worldwide registry of >10 000 CAS procedures, the use of EPDs halved the event rates.8 As a possible confounding factor, the use of an EPD likely occurred at a later stage of the operator’s learning curve. Advantages and disadvantages of CAS are listed in Table 2.
Decision Making in Carotid Revascularization
The Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) compared CEA and carotid angioplasty in patients at low to moderate risk for surgery.9 A total of 504 patients with symptomatic carotid stenosis were randomized to CEA or angioplasty.9 The incidence of death or stroke at 30 days was 10% in the endovascular group and 9.9% in the surgical group. The outcomes among the 2 groups remained comparable at 3 years. The study was criticized by the interventionalist community for the low stenting rate (26%) and by surgeons for the high event rates in the surgical arm. Currently, several randomized trials are underway that compare CAS and CEA in low-risk patients, including the US National Institutes of Health–sponsored Carotid Revascularization Endarterectomy Versus Stent Trial (CREST). Until these results become available, low-risk patients should be treated with CAS only within studies.
The Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial is the first and currently only randomized trial comparing CEA and CAS with EPD.10 The study focused on patients at high risk for surgery with ≥50% symptomatic or ≥80% asymptomatic carotid stenosis. Among the 334 patients randomized, major adverse events occurred in 12.2% in the stent group and in 20.1% in the CEA group (P=0.053) at 1 year (Figure 2). In addition, the need for repeat carotid revascularization was lower in the CAS group than in the CEA group (0.6% versus 4.3%; P=0.04). For the first time, nonfatal cardiac events were included in the outcome analysis of a carotid revascularization trial. Patients who underwent CAS had significantly fewer myocardial infarctions at 30 days compared with those who were randomized to CEA (1.9% versus 6.6%; P=0.04). Prospective registries including almost 4000 protected CAS procedures, performed mainly in high-risk patients, resulted in 30-day death, myocardial infarction, or stroke rates ranging between 3.4% and 7.8%.11 On the basis of the current evidence, CAS with EPD in the hands of experienced operators should be considered equal if not superior to CEA in this patient population.
Current CMS Guidelines
In the United States, the CMS has concluded that CAS with EPD is reasonable and appropriate for symptomatic patients with carotid stenosis ≥70% at high risk for surgery (Table 1).12 If performed within clinical trials or CAS postapproval studies, the procedure may be performed in high-risk symptomatic patients with 50% to 70% stenosis and in high-risk asymptomatic individuals with stenosis ≥80%. Carotid stenting is considered appropriate if performed in facilities and by operators complying with the set standards.12 A suggested management strategy for patients with carotid stenosis is illustrated in Figure 3.
CAS has emerged as alternative treatment to CEA in patients with carotid stenosis. Current evidence suggests that using an EPD markedly reduces the number of neurological events. In patients at high risk for surgery, the SAPPHIRE trial has shown that protected CAS is equal if not superior to surgery in the hands of experienced operators. Ongoing randomized trials, including CREST, are investigating the role of CAS in low-risk patients. In the United States, CMS guidelines currently support protected CAS for patients at high risk for surgery with symptomatic carotid stenosis ≥70%. Because of the presence of a contralateral carotid occlusion, the patient discussed earlier was considered at high risk for surgery. He was offered both CEA and CAS but preferred the endovascular approach. After clopidogrel loading, he underwent uneventful protected CAS of the right internal carotid artery. At the 1-year follow-up, he was free of recurrent neurological events and restenosis.
Heart Disease and Stroke Statistics–2006 Update. Dallas, Tex: American Heart Association; 2006.
Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: asymptomatic carotid surgery trial. Stroke. 2004; 35: 2425–2427.
Biller J, Feinberg WM, Castaldo JE, Whittemore AD, Harbaugh RE, Dempsey RJ, Caplan LR, Kresowik TF, Matchar DB, Toole JF, Easton JD, Adams HP Jr, Brass LM, Hobson RW 2nd, Brott TG, Sternau L. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association. Circulation. 1998; 97: 501–509.
Kastrup A, Groschel K, Krapf H, Brehm BR, Dichgans J, Schulz JB. Early outcome of carotid angioplasty and stenting with and without cerebral protection devices: a systematic review of the literature. Stroke. 2003; 34: 813–819.
CMS decision memo for carotid artery stenting (CAG-00085R). Available at: http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=157. Accessed December 12, 2005.