Carotid Artery Stenosis

Current and Emerging Treatments

Seemant Chaturvedi, Peter M. Rothwell

• Publisher: CRC Press
• Year: 2005
• ISBN:
  9781135534745
• Edition: 1
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

Providing a thorough overview of rapid developments in medical therapy, surgery, and angioplasty, this reference provides a complete review of carotid artery stenosis treatment, as well as a clear overview of carotid surgery and stenting. Offering chapters by seasoned authorities on epidemiology, imaging with ultrasound and angiography, cholesterol

1
Introduction

Peter M.Rothwell

Stroke Prevention Research Unit, University Department of Neurology, University of Oxford, Radcliffe Infirmary, Oxford, U.K.

Seemant Chaturvedi

Department of Neurology, Detroit Medical Center, Wayne State University, Detroit, Michigan, U.S.A.

Somewhere between 15 and 20% of patients presenting with transient ischemic attack (TIA) or non-disabling ischemic stroke have a significant stenosis at or around the bifurcation of the ipsilateral carotid artery and about 5–10% of asymptomatic elderly individuals have significant stenosis of at least one carotid artery. The purpose of this book is to summarize current knowledge about the natural history and optimal treatment of patients with carotid disease and to consider future directions for research and therapy. However, it is appropriate to first briefly review how our current understanding and practice have developed. The recent history of the development of medical treatments for vascular disease is well known and so we have confined ourselves to a brief review of the history of our understanding of the role of carotid stenosis in causing TIA and stroke, and of the development of surgical and endovascular treatment.

1. PATHOPHYSIOLOGY

The knowledge of the relationship between atheromatous disease of the extracranial carotid and vertebral arteries and the occurrence of ischemic stroke goes back to the nineteenth century. In 1856, Virchow described carotid thrombosis in a patient with sudden onset ipsilateral visual loss in whom the ophthalmic and retinal arteries were patent (1). In 1888, Penzoldt reported a patient who had developed sudden permanent loss of vision in the right eye and later sustained a left hemiplegia (2). At post-mortem she was found to have had thrombotic occlusion of the right distal common carotid artery and a large area of cerebral softening in the right cerebral hemisphere. In 1905, Chiari performed a number of pathological studies which led him to suggest that emboli could break away from ulcerated carotid plaques in the neck and cause cerebral infarction(3,4). Clinical research on carotid disease was given a major boost by the development of cerebral arteriography by Egas Moniz in 1927 (5), and the subsequent demonstration of stenosis and occlusion of the carotid arteries in life (6,7).

The hypothesis that carotid disease was an important cause of ischemic stroke and that thromboembolism was the predominant mechanism was re-emphasized in the 1950s and 1960s by Miller Fisher (8,9). The work of Fisher and others prompted the development in the 1950s and 1960s of several operative techniques, the aim of which was to restore the flow of blood to the brain in patients with stenosis or occlusion of the extracranial carotid or vertebral circulations (10). The development of extracranial/intracranial (EC/IC) bypass surgery and carotid endarterectomy are described below. Several other surgical techniques have been tried, although unlike endarterectomy and EC/IC bypass, they have not been tested in randomized controlled trials. These include various bypass procedures for occlusion of the proximal neck and aortic arch vessels (11), vertebral artery endarterectomy, reconstruction or bypass (12), and various arterial transpositions involving anastomosis of the subclavian and vertebral arteries into the common carotid artery (13).

Patients with complete occlusion of the internal carotid artery are not suitable for carotid endarterectomy or angioplasty. Patients with symptomatic carotid occlusion have an annual risk of ipsilateral ischemic stroke of around 5% (14,15). Many of these strokes are likely to be caused by embolism from the occluded carotid artery, but there is evidence that cerebral hypoperfusion is also important (16,17). With developments in micro-surgical techniques in the 1960s, it became possible to perform EC/IC bypass surgery in such patients in order to increase cerebral perfusion (18). The most commonly performed procedure involved anastomosis of branches of the superficial temporal artery to the middle cerebral artery. This operation became very popular for symptomatic carotid occlusion in the 1970s and early 1980s. As a consequence of this, a large randomized controlled trial was performed (19). Although EC/IC bypass does appear to be effective in increasing cerebral perfusion in some patients (20), the trial reported no reduction in the risk of stroke. Since the trial was reported in 1985, the use of EC/IC bypass surgery has declined dramatically. However, recent studies have suggested that it is possible to identify a subgroup of patients with carotid occlusion who have severe cerebral hypoperfusion and a particularly high risk of ipsilateral ischemic stroke (21,22). Further randomized trials are ongoing in this subgroup (23).

2. EARLY CAROTID SURGERY

Carotid endarterectomy was introduced in the 1950s and became popular in the 1970s and early 1980s, but it was not until 1991 that it was shown to be of value in patients with a recently symptomatic 70–99% carotid stenosis (24,25). However, the history of carotid artery surgery goes back much further. The first operations on the carotid artery were ligation procedures for trauma or hemorrhage. The first report was in Benjamin Bell’s surgery in 1793 (26). However, most early ligations resulted in the death of the patient. The first successful ligation was performed by a British naval surgeon, David Fleming, in 1803 (27). This operation was performed for late carotid rupture following neck trauma in an attempted suicide. The first successful ligation for carotid aneurysm was performed five years later in London by Astley Cooper (28). By 1868, Pilz was able to collect 600 recorded cases of carotid ligation for cervical aneurysm or hemorrhage with an overall mortality of 43% (29). In 1878, an American surgeon named John Wyeth reported a 41% mortality in a collected study of 898 common carotid ligations, and contrasted this with a 4.5% mortality for ligation of the external carotid artery (30).

There were relatively few developments for the next 70 years. However, in 1946, a Portuguese surgeon, Cid Dos Santos, introduced thromboendarterectomy for the restoration of flow in peripheral vessels (31). The first successful reconstruction of the carotid artery was performed by Carrea et al., in Buenos Aires in 1951 (32). However, this was not an endarterectomy. Rather they performed an end-to-end anastomosis of the left external carotid artery and the distal internal carotid artery in a man of 41 with a recently symptomatic severe carotid stenosis.

3. CAROTID ENDARTERECTOMY

There is a debate about who performed the first true carotid endarterectomy. In 1954, Eastcott et al., published a case report detailing a carotid resection performed in May 1954 on a 66-year-old woman with recurrent left carotid TIAs and a severe stenosis on angiography (33). The patient made an uneventful recovery and was relieved of her TIAs. However, in 1975, DeBakey reported that he had performed a carotid endarterectomy on a 53-year-old man in August 1953 (34). However, it was the report by Eastcott et al., which provided the impetus for the further development of carotid surgery. Over the next five years there were numerous other reports of the operation being performed and several technical improvements were suggested. The operation became extremely popular in the 1960s and 1970s. By the early 1980s there were over 100,000 procedures per year in the USA alone (35). However, at this point in time, there was no evidence from randomized controlled trials that the operation was of any value. This prompted several eminent clinicians to question the widespread use of the operation in the early 1980s (36–39) which led to a fall in the number of operations being done and set the scene for a number of large, randomized controlled trials.

There have been five randomized controlled trials of carotid endarterectomy for symptomatic carotid stenosis (24,25,40–42). The first two studies were relatively small and did not produce reliable results (40,41). The larger VA Cooperative Symptomatic Carotid Stenosis Trial (VA #309) reported a non-significant trend in favor of surgery (42), but was stopped in 1991 when the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET) demonstrated a clear reduction in the overall risk of stroke in operated patients with recently symptomatic severe (70–99%) carotid stenosis (24,25). The final report from the NASCET and a subsequent pooled analysis of individual patient data from all trials showed that endarterectomy was also of benefit in patients with recently symptomatic 50–69% stenosis (43,44). However, other research done in parallel has shown that the benefit also depends to a significant extent on other clinical characteristics (45–47).

4. CAROTID ANGIOPLASTY

Transluminal angioplasty was first used in the limbs in the 1960s (48), and then subsequently in the renal and coronary arteries. Angioplasty was introduced cautiously in the cerebral circulation because of fears of plaque rupture and embolism causing stroke. Angioplasty of stenoses of the proximal vertebral artery (49), the basilar artery (50), the distal internal carotid artery and proximal middle cerebral artery stenosis (51,52), were performed in the 1980s. During the past 10 years angioplasty and stenting at the carotid bifurcation has increased in popularity and is now under investigation as a potential alternative to endarterectomy. Thus far, there have been five small randomized controlled trials of angioplasty +/- stenting vs. endarterectomy (53–57). Taken together they suggest that angioplasty +/- stenting is associated with a similar procedural risk to endarterectomy but a possibly increased rate of restenosis. However, improvements in cerebral protection devices may reduce the procedural risks (58), and several further trials of angioplasty and stenting with cerebral protection vs. endarterectomy are ongoing.

5. INTERVENTION FOR ASYMPTOMATIC CAROTID STENOSIS

About 5–10% of the general population aged over 60 years have at least one asymptomatic carotid stenosis (59). However, the natural history of asymptomatic carotid stenosis was only reliably defined in large studies in the 1980s when carotid ultrasound became available. Several large studies showed that the prognosis was much more benign than that of recently symptomatic stenosis, with a risk of ipsilateral ischemic stroke of less than 2% per year in patients with severe asymptomatic stenosis (60,61). Despite inconclusive results from some small early randomized trials of endarterectomy for asymptomatic carotid stenosis vs. medical treatment alone (62–65), the number of operations done for asymptomatic stenosis in North America increased dramatically in the 1980s (35). In 1993, the VA trial demonstrated a significant reduction in the risk of the combined outcome of stroke and TIA in the endarterectomy group, but did not have the power to demonstrate a reduction in the risk of stroke alone (66). In 1995, the Asymptomatic Carotid Artery Study (ACAS) (67) demonstrated a clearly significant reduction in the risk of ipsilateral ischemic stroke in patients with 60–99% asymptomatic stenosis: a reduction in the five-year actuarial risk of ipsilateral ischemic stroke or operative death from 11 to 5.1% (p<0.001). Unlike the ECST and NASCET trials, the ACAS trial included the risks of stroke and death due to carotid angiography in the overall outcome. However, the operative risk of stroke and death due to endarterectomy was much lower than in the randomized controlled trials of endarterectomy for symptomatic stenosis, an observation that was confirmed by analyses of case series from routine clinical practice (68). More recently, the much larger Asymptomatic Carotid Surgery Trial (ACST) showed a very similar absolute benefit to that in ACAS, despite a higher operative risk (69). Several questions remain, particularly about the benefit of surgery in specific subgroups, the potential for selection of patients on the basis of an increased risk of stroke without surgery, and the long-term benefits of surgery (70), but there is no doubt that endarterectomy for asymptomatic stenosis is of modest overall benefit. Whether it is a cost effective intervention and whether screening will do more good than harm are less certain (71).

6. CONCLUSIONS

Considerable progress was...

Table of contents

• Cover Page
• Neurological Disease and Therapy
• Title Page
• Copyright Page
• Preface
• Contributors
• 1 Introduction
• 2 Epidemiology of Carotid Artery Stenosis
• 3 Pathophysiology
• 4 Carotid Imaging—Is Angiography Still Needed?
• 5 Carotid Imaging: Use of Ultrasound
• 6 Antithrombotic Therapy for Carotid Artery Stenosis
• 7 Stroke Prevention, Blood Cholesterol, and Statins
• 8 Management of Hypertension in Carotid Stenosis
• 9 Hyperhomocyst(e)inemia and Carotid Atherosclerosis
• 10 Diet in the Management of Patients with Carotid Stenosis
• 11 Angiogenesis and Angiogenic Growth Factors as Future Therapies for Cerebrovascular Disease
• 12 What Are the Current Operative Risks of Carotid Endarterectomy?
• 13 Benefits of Endarterectomy for Recently Symptomatic Carotid Stenosis
• 14 Management of Carotid Artery Disease: Carotid Endarterectomy for Asymptomatic Carotid Stenosis
• 15 Surgical Controversies
• 16 Symptomatic Carotid Artery Occlusion: Extracranial Intracranial Bypass and Other Treatment Options
• 17 Stenting for Symptomatic Stenosis
• 18 Stenting for Asymptomatic Stenosis
• 19 Angioplasty and Stenting for Non-atherosclerotic Diseases of the Carotid Artery
• 20 Controversies in Endovascular Therapy for Carotid Artery Stenosis