Management of Asymptomatic Extracranial Carotid Artery Disease

Introduction

The stroke risk and management principles for symptomatic internal carotid artery (ICA) stenosis are relatively well established and have a wide consensus among practicing clinicians, discussed in Chapter 80 . The same, however, cannot be said for management of asymptomatic carotid stenosis (ACS), which is a more complex and challenging issue. An extensive in-depth analysis exceeds the scope of this chapter, but we will present the salient points of our understanding of ACS, as it has evolved over the years.

Epidemiology

Extracranial ICA atherosclerosis is an important potentially treatable cause of ischemic stroke. Its prevalence in the population increases with age: in men younger than 50 years the prevalence of moderate stenosis is 0.2% and of severe stenosis is 0.1%, whereas in women of the same age the prevalence is very close to 0% . In contrast, moderate stenosis (50–74%) was found in ∼7% of men and ∼5% of women older than 65 years . The percentages for severe stenosis (75–100%) were 2.3% and 1.1%, respectively . In population-wide scale, approximately 7–10% of all first ischemic strokes is associated with extracranial carotid stenosis of > 60% . Its relative contribution to ischemic stroke is considerably higher in the black people (attributable incidence of 17 in 100,000) than in the Hispanic population (9 in 100,000) and the white people (5 in 100,000) .

Revascularization

In cases of recently symptomatic hemodynamically significant ICA stenosis, the risk of recurrent stroke increases in proportion to the degree of vessel stenosis, and in general, CEA is recommended for patients with stenosis of 70% or more. The role of revascularization in ACS is less straightforward.

Carotid Endarterectomy

The first evidence of the benefit of using carotid endarterectomy (CEA) in addition to medical management in ACS was provided by a clinical trial of 444 patients recruited from 10 US Veterans Affairs medical centers , and it was followed by two large-scale studies in the United States and Europe:

The Asymptomatic Carotid Atherosclerosis Study (ACAS) was conducted between 1987 and 1993 in the United States and Canada. A total of 1662 patients with 60–99% carotid stenosis and no clinical symptoms suggestive of TIA or stroke were randomized to receive maximum medical management versus maximal medical management plus CEA. The study reached the significance boundary after 2.7 years of median follow-up when only 9% of the patients had completed the 5-year follow-up. The imputed 5-year risk of ipsilateral stroke or death in the medical arm was 11% versus 5.1% in the CEA arm [relative risk reduction (RRR), 53%; p = .004; confidence interval (CI), 22–72%]. The 30-day perioperative risk rate of death and stroke in those who underwent CEA was 2.3%.

The international Asymptomatic Carotid Surgery Trial (ACST) was conducted between 1993 and 2003. The investigators randomized 3120 patients with ACS of 60–90% to either immediate CEA or deferral of any CEA in a 1:1 ratio. The results essentially mirrored those of the ACAS study: the 5-year risk rate of any type of stroke or perioperative mortality was 6.4% in the CEA group compared to 11.8% in the CEA deferral group ( p < 0.0001; 95% CI, 2.96–7.75). An increase in early mortality in the CEA group caused by perioperative risk was counterbalanced and eventually overturned by a higher, but more evenly distributed, number of endpoint events in the medical arm. This statistically significant net reduction of stroke and death of ∼5% was maintained in the 10-year follow-up which suggests that the benefit from CEA was achieved in the early to mid-term follow-up period as the rate of endpoint events remained comparable in the 5- to 10-year follow-up period. The 30-day risk rate of stroke or death was 3.1%.

Carotid Artery Stenting

No study has specifically explored the efficacy of carotid artery stenting (CAS) versus medical management in carotid stenosis, and no study with published results was devoted to asymptomatic patients only. However, patients with ACS were included in most CAS trials. The early carotid angioplasty and stenting trials were discouraging, with relatively high periprocedural risk rates of stroke and mortality. In the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) , the 4-year risk rate of stroke among patients with ACS undergoing CEA was 2.7% versus 4.5% with a periprocedural risk rate of 1.4% versus 2.5%. Therefore CAS is used as an alternative to CEA in select cases, especially in cases with challenging anatomy and vasculature.

Ongoing Trials

A large phase 3 multicenter trial in Europe, Africa, Asia, and North America is currently underway (ACST-2, ISRCTN 21144362), comparing CEA and CAS for long-term stroke prevention in patients with ACS of ≥ 70%. The study aims to recruit 3600 patients by 2019 and follow them for 5–10 years.

The CREST-2 trial (NCT02089217) consists of two parallel multicenter randomized trials conducted in the United States and Canada with an enrolment target of 2480 patients. One trial is comparing intensive medical management alone with intensive medical management plus CEA, whereas the parallel arm is comparing medical management alone with CAS plus medical management.

Official Guidelines and Current Status of Practice

Based on the ACAS and ACST findings, revascularization has been recommended for moderate and severe ACS in select cases and this has led to practice changes, especially in the United States . A caveat is that selection criteria are not specified, which has allowed a rather loose interpretation and implementation of the guidelines. As a result, a large number of CEAs have been and continue to be performed on the basis of angiographic findings only, without further stratification of stroke risk.

However, as we will see, a closer look at the specific details of these trials, along with other factors, challenges a simplistic, “one-size-fits-all,” mass intervention stance.

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