8 carotid artery 1 intervention - springerextras.springer.com › 2007 › 978-1-84628-188-4 ›...

1741

Carotid Artery Intervention

Christopher J. White

Key Points

• The pathophysiology of stroke secondary to carotid artery atherosclerotic disease is most commonly atheroembolic in nature.

• Carotid artery dissection is the second most common cause of stroke in the young and middle-aged populations.

• The most consistent single risk factor for perioperative cerebrovascular complications is a past history of stroke.

• In patients with both coronary and carotid artery disease and in whom one lesion is symptomatic and one lesion is asymptomatic, the symptomatic lesion should be treated fi rst as a staged procedure.

• Because the perioperative stroke risk is so low in a patient undergoing general surgery with an asymptom-atic carotid stenosis, prophylactic revascularization is not recommended.

• A recent trial suggested that while ultrasound is an excel-lent screening tool for carotid disease, its accuracy in a community hospital setting was not suffi cient to replace angiography.

• The cost-to-benefi t profi le for carotid duplex imaging makes it the imaging modality of choice for detection of carotid in-stent stenosis with acceptable sensitivity, patient accessibility, no ionizing radiation exposure, and no need for radiographic contrast.

• Computed tomography angiography (CTA) appears to be superior to magnetic resonance angiography (MRA) for in-stent stenosis detection for both nitinol and stainless steel stents.

• The CAPRIE trial did not show a reduction in stroke risk with clopidogrel compared to aspirin alone.

• The MATCH trial showed no stroke reduction benefi t for aspirin and clopidogrel compared to clopidogrel alone, although there was increased bleeding risk with the com-bination therapy.

• The preponderance of evidence is that the addition of dipyridamole to aspirin for primary or secondary stroke prevention is of marginal benefi t.

• Despite the absence of epidemiologic data to link elevated cholesterol levels with stroke, large studies of several statins have demonstrated stroke reduction with this class of drugs.

• Carotid endarterectomy (CEA) is the established surgical procedure for stroke prevention in patients with extracra-nial carotid artery disease and is superior to medical therapy for symptomatic lesions of ≥50% stenosis and asymptomatic lesions of ≥60% stenosis.

• Carotid artery stent (CAS) placement is as good as or better than carotid surgery for stroke prevention in symptomatic (≥50% narrowing) and asymptomatic (≥80% narrowing) patients at increased risk of surgical complications.

• The use of emboli protection devices appears to reduce the risk of embolic stroke during the procedure, but ran-domized trials have not yet proven their benefi t.

• Guidelines for training and credentialing physicians via the training pathway or the clinical pathway have been developed and endorsed by multiple medical societies.

• The Medicare reimbursement strategy for carotid stents is not consistent with the published trial data and limits carotid stenting to Food and Drug Administration (FDA)-approved preclinical trials, postmarket surveillance trials, and symptomatic patients with a ≥70% carotid stenosis who are at high risk of complications during carotid surgery.

Background/History

The era of percutaneous revascularization techniques was ushered in by Charles Dotter1 in 1964, and then pushed forward by Gruntzig2 with the invention of the balloon dila-tion catheter. The technique of percutaneous transluminal angioplasty (PTA) has been used in both peripheral and coro-nary vessels to great success, and in many circumstances has largely replaced surgical therapy as the fi rst treatment choice. The use of PTA in the extracranial carotid circulation began in Europe with a multispecialty interest including

81

Background/History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1741Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1742Recognition of the Clinical Problem . . . . . . . . . . . . . . . 1743Diagnostic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1744Evidence-Based Medicine: Stroke Prevention . . . . . . . . 1745

Comparative Clinical Trials: Stroke Prevention. . . . . . 1747Carotid Stent Guidelines. . . . . . . . . . . . . . . . . . . . . . . . . 1750The Author's Use of This Information in Clinical

Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1751Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1751

CAR081.indd 1741CAR081.indd 1741 11/24/2006 12:12:26 PM11/24/2006 12:12:26 PM

174 2 c h a p t e r 81

cardiology, radiology, vascular surgery, and neurology.3,4 Interestingly, in a worldwide survey of carotid intervention published in 1998, the specialty of cardiology was dominant, responsible for more than 60% of all the reported cases.5 Cardiologists have continued to lead this fi eld with the devel-opment of embolic protection devices (EPDs), initially proven in saphenous vein graft intervention; cardiologists are already comfortable with using this technology.6–9

Pathophysiology

Atherosclerosis

The underlying cause of the majority of cerebral ischemic events in the United States and Europe and of cerebral isch-emia is a focal manifestation of a systemic disease—athero-sclerosis. Extracranial atherosclerotic carotid artery disease accounts for slightly more than half of the 731,000 strokes per year in the United States. Stroke is the third leading cause of death after coronary artery disease and cancer in the United States and it is the leading cause of disability. In the Framingham study, 70% of the stroke patients had hyper-tension, 70% had coronary artery disease, and 30% had peripheral vascular disease.

There are two main types of stroke: ischemic and hemor-rhagic. Ischemic stroke results from a reduction or occlusion of blood fl ow due to emboli, thrombosis, or hypoperfusion. Hemorrhagic stroke includes primary cerebral hemorrhages or hemorrhage secondary to an ischemic event. Atheroscle-rotic carotid artery stenoses most often cause symptoms due to emboli events (Fig. 81.1). A minority of ischemic strokes are caused by thrombotic occlusion, which is in contrast to acute coronary syndromes, which are usually due to throm-botic vessel occlusion.

Anatomically, the two internal carotid arteries and two vertebral arteries come together at the base of the skull to form the circle of Willis, which is the most ideal anastomotic network in the body (Fig. 81.2). In theory, a single vessel could supply the circulatory needs of the entire brain. However, while the circle of Willis is present in every brain, there is a huge amount of individual variability, and fewer than half are complete.

Fibromuscular Dysplasia

Fibromuscular dysplasia (FMD) is classifi ed based on the arterial layer involved: intimal, medial, and adventitial.10 Medial fi broplasia is the most common form and is charac-terized angiographically by its “string of beads” appearance (Fig. 81.3). Typically the dilated segments (beads) are larger than the normal artery and are located in the middle or distal segment of the artery. Fibromuscular dysplasia has a predilection for females and whites, and is usually bilateral. Carotid artery FMD is usually discovered in patients in the fi fth decade of life.11 When FMD is found in the cervical carotid artery, intracranial aneurysms are commonly noted. The natural history of cerebrovascular FMD of the medial type is generally benign.12 For symptomatic lesions that have failed antiplatelet therapy, percutaneous therapy is preferred over surgery, although there are no controlled trials to support this recommendation.13 Typically, balloon angioplasty is performed with stent placement reserved for “bailout” situations.

FIGURE 81.1. Carotid artery angiogram showing a critical stenosis at the origin of the internal carotid artery and a stenosis at the origin of the external carotid artery.

FIGURE 81.2. Schematic diagram of the circle of Willis. ACA, anterior cerebral artery; MCA, middle cerebral artery; PCA, poste-rior cerebral artery; P Com, posterior communicating artery; AICA, anterior inferior cerebellar artery; PICA, posterior inferior cerebel-lar artery.


c a ro t i d a rt e ry i n t e rv e n t ion 174 3

Carotid Artery Dissection

Spontaneous dissections of the carotid or vertebral arteries account for only 2% of all strokes, but are the second most common cause of stroke in young and middle-aged patients.14 There is a peak in the fi fth decade of life without a sex pre-dilection. Typically the patient presents with pain on one side of the head, accompanied by a partial Horner’s syndrome (miosis and ptosis), which is usually accompanied by cerebral or retinal ischemia. Anatomically, the dissection typically starts a short distance distal to the carotid bulb (Fig. 81.4). Magnetic resonance angiography (MRA) and computed tomo-graphic angiography (CTA) are replacing angiography as the imaging studies of choice in carotid dissection. Doppler ultrasound of the neck may also be helpful, although it is limited to viewing the cervical portion of the artery.

The prognosis for carotid dissections is related to the severity of the cerebral ischemia and the ability of the circle of Willis to provide collateral fl ow. Dissections are dynamic processes with eventual resolution of the stenoses in 90% of cases, recanalization of occlusions in 67%, and shrinking of aneurysms in 33%.14 There is no difference in the risk of stroke, which is low, in patients with a transient or perma-nent residual severe stenosis or occlusion.15

The conventional treatment of carotid dissection is anti-coagulation (heparin and coumadin) or antiplatelet therapy

for 3 to 6 months. A recent meta-analysis was unable to dem-onstrate superiority of one regimen over the other.16 Revascu-larization with surgery, angioplasty, or stents should be reserved for those patients with persistent or recurrent symp-toms of ischemia, despite therapeutic anticoagulation.14

Recognition of the Clinical Problem

Cerebrovascular Symptoms

Symptomatic cerebrovascular events are classifi ed as tran-sient ischemic attacks (TIAs) if they completely resolve within 24 hours, or strokes if they leave a permanent defi cit. Approximately 5% of patients suffering a TIA will have a stroke within 30 days, and almost one fourth of TIA patients will have a recurrent event within a year. Symptoms may be “hemispheric,” meaning they are related to a single carotid distribution, causing contralateral hemiparesis or hemipar-esthesia, aphasia, or ipsilateral monocular blindness (amau-rosis fugax), or they may be nonhemispheric, with symptoms

FIGURE 81.3. Computed tomography angiography (CTA) image of fi bromuscular disease with a classic “string of beads” appearance of the internal carotid artery.

FIGURE 81.4. Carotid dissection showing abrupt cutoff (arrow) of the proximal internal carotid artery.


174 4 c h a p t e r 81

of vertebrobasilar insuffi ciency (VBI) such as dysarthria, dip-lopia, vertigo, syncope, or transient confusion.

Preoperative Assessment

As the population ages, increasing numbers of elderly patients will be considered for a variety of surgical procedures. There is a direct relationship between age and cerebrovascular disease that needs to be considered when assessing a patient’s operative cardiovascular and stroke risk.17 Potential intraop-erative and perioperative stroke mechanisms include (1) sys-temic hypotension, causing cerebral hypoperfusion, which results in a “watershed” stroke; (2) atheroembolism from carotid or aortic wall plaque; (3) thromboembolism from the left atrium or perhaps via patent foramen ovale; and (4) hema-tologic factors related to a hypercoagulable state. Most authorities consider the risks of cardiac and noncardiac sur-geries separately because of the more generalized atheroscle-rosis present in cardiac surgery patients, which increases the risk of stroke. The most consistent single risk factor for peri-operative cerebrovascular complications is a past history of stroke. For patients undergoing coronary artery bypass graft (CABG) surgery, a past history of stroke or TIA increases the risk of stroke by a factor of four.18

Patients with an asymptomatic bruit, found prior to non-cardiac surgery, should undergo a detailed neurologic evalu-ation. If no symptoms or signs of focal cerebral ischemia are found, general surgery may be performed without further evaluation of the carotid arteries. Because the stroke risk is so low in a patient undergoing general surgery with an asymptomatic carotid stenosis, prophylactic revasculariza-tion is not recommended. Patients being considered for cardiac surgery and found to have an asymptomatic carotid bruit on physical examination should undergo a noninvasive imaging study to determine the severity of the lesion. Patients with severe stenoses, >80%, may be considered candidates for revascularization with carotid artery stent (CAS) or carotid endarterectomy (CEA).

Patients with symptomatic carotid stenoses should be evaluated with noninvasive imaging studies as part of their preoperative assessment. A patient with a symptomatic mod-erate to severe (>50%) carotid stenosis should be revascular-ized by CAS or CEA prior to elective cardiac or general surgery. But a patient who sustained a moderately large stroke should wait at least 1 month before undergoing elec-tive surgery.

It is important to remember that a successful CEA or CAS procedure for a severe carotid stenosis will not entirely remove the perioperative risk of stroke. For semi-urgent CABG patients with critical (>80% diameter) asymptomatic carotid stenoses, a staged procedure with CAS as the fi rst choice is preferred to combined CEA and CABG. In these patients several weeks of aspirin and clopidogrel are desirable after carotid stent placement. In patients with both coronary and carotid artery disease in whom one lesion is symptomatic and one lesion is asymptomatic, the symptomatic lesion should be treated fi rst as a staged procedure. Combined CEA and CABG procedures generally result in higher rates of stroke or death than staged procedures. In patients with both cardiac and carotid symptomatic lesions, a staged procedure with CAS fi rst is preferred over combined CEA and CABG.19

Diagnostic Testing

Noninvasive Imaging

Doppler ultrasound or Duplex imaging of the extracranial carotid arteries is cost-effective, accurate, and reproducible. Duplex imaging of the carotids provides information about the location, extent, and severity of disease. Blood fl ow veloc-ity measurements are translated into categories that have clinical relevance. There is controversy regarding the ability of ultrasound imaging to serve as the sole imaging criteria for carotid revascularization.20,21 A recent trial suggested that while ultrasound is an excellent screening tool, its accuracy in a community setting was not suffi cient to replace angiog-raphy.22 As the resolution and speed of MRA and CTA are rapidly improving, they are being used to image the extra-cranial carotid arteries and intracerebral vessels (Fig. 81.5).23,24 The images can be reconstructed into noninvasive angio-grams that have the advantage of imaging the Circle of Willis with excellent resolution and clarity.25,26

FIGURE 81.5. Computed tomography angiography of the aortic arch and left carotid artery.



Invasive Angiography

All of the revascularization trials on which carotid artery treatment decisions have been based have used angiographic criteria for patient selection.27 Invasive angiography is the gold standard for the diagnosis of vascular pathology of the aortic arch, cervical, and cerebral vessels. The major draw-back for invasive angiography has been the risk of adverse events associated with the procedure. In the Asymptomatic Carotid Artery Surgery (ACAS) trial, there was a 1.2% risk of stroke related to angiography performed by radiologists.28 More recently, we have reported a much lower (0.5%) stroke rate for experienced interventional cardiologists performing carotid angiography.29 Clearly, clinical volume, technical skills, and patient selection are important elements in mini-mizing the risk for diagnostic angiography.

Follow-Up Carotid Stent Surveillance

Despite a very low restenosis rate, carotid stent patency should be followed noninvasively.30,31 Carotid Duplex imaging may be hampered by other technical diffi culties such as dense calcifi cation causing acoustic shadowing, a problem not infrequent in patients with severe carotid stenosis. In addition, the presence of excessive tortuosity, a high bifurca-tion, or a short neck may interfere with obtaining the appro-priate ultrasound window and velocity measurement.25 Finally, in patients with high-grade stenosis, blood fl ow in residual lumen may not be detected because of sonographic absorption by the atheroma.32

The cost-to-benefi t profi le for carotid Duplex imaging makes it the imaging modality of choice for detection of carotid in-stent stenosis with acceptable sensitivity, patient accessibility, no ionizing radiation exposure, and no need for radiographic contrast.33 In subjects with appropriate anatomy and a lack of heavy calcifi cation, a normal duplex study will obviate the need for further investigation.

Computed tomography angiography has the ability to examine the carotid stent lumen even in the face of dense calcifi cation of carotid plaque. In subjects with a tortuous carotid, short neck, or high bifurcation, CTA is the imaging modality of choice for surveillance imaging, even with the capability of diagnosing mild intimal hyperplasia after stent-ing (Fig. 81.6).25 In a comparison study of CTA, duplex, and invasive angiography, a better correlation was demonstrated between CTA and invasive angiography than between duplex and invasive angiography.26

The disadvantages of CTA include the need for ionizing radiation and the use of iodinated contrast material. This is of concern in patients at risk for renal insuffi ciency, that is, patients with diabetes mellitus, and the aging population is at increased risk for extracranial carotid artery disease. In these situations, CTA should be reserved for cases with an indeterminate duplex examination.

Another imaging alternative is MRA, which is noninva-sive, dose not require any radiation or iodinated contrast, and offers high-resolution imaging. The use of MRA for evalua-tion of in-stent restenosis has been hampered by radiofre-quency shielding artifact related to the metallic composition of the stent.34 Nonferromagnetic stents of nitinol and tanta-lum cause less artifact than cobalt and stainless steel stents.

Computed tomography angiography appears to be superior to MRA for in-stent stenosis detection for nitinol and stainless steel stents.35

Invasive angiography remains the gold standard for assessment or carotid artery stent patency, and any patients with evidence of in-stent restenosis by other modalities will require angiography for further evaluation. We suggest duplex as the fi rst surveillance test to evaluate patency of a carotid artery stent. If the results of the duplex are inconclusive, proceed with CTA (based on the superiority of CTA over MRA for nitinol stents). An abnormal result in either of these modalities should be confi rmed by invasive angiography.

Evidence-Based Medicine: Stroke Prevention

Pharmacologic Therapy

Both primary and secondary stroke prevention require aggressive risk factor modifi cation, specifi cally blood pres-sure control and smoking cessation. Aspirin therapy (75 to 325 mg) daily, results in a 25% relative risk reduction com-pared to placebo.36,37 There is consensus that doses of aspirin >325 mg per day are not more effective for stroke preven-tion.38 The Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial demonstrated a signifi cant benefi t for clopidogrel for the combined end point of ischemic stroke, myocardial infarction, or vascular death, but it did not show a reduction in stroke risk with clopidogrel com-pared to aspirin alone.39 The Management of ATherothrom-bosis with Clopidogrel in High-risk patients (MATCH) trial showed no stroke reduction benefi t for aspirin and clopido-grel compared to clopidogrel alone, although there was increased bleeding risk with the combination therapy.37 Despite isolated data from a single trial regarding secondary prevention, the preponderance of evidence is that the addi-

FIGURE 81.6. Computed tomography angiography of in-stent restenosis.


174 6 c h a p t e r 81

tion of dipyridamole to aspirin alone for primary or second-ary stroke prevention is of marginal benefi t.36,37,40 There are no data to support the role of anticoagulation with warfarin to reduce the risk of stroke in patients without atrial fi brillation.41

Despite the absence of epidemiologic data to link elevated cholesterol levels with stroke, large studies of several statins have demonstrated stroke reduction with this class of drugs.42 Both the Scandinavian Simvastatin Survival Study (4S) trial with simvastatin and the Cholesterol and Recurrent Events (CARE) trial with pravastatin demonstrated a 30% relative risk reduction for stroke compared to placebo.43,44 Of interest, the stroke benefi t did not appear in these trials until after 3 years of therapy.

Surgical Treatment

Carotid endarterectomy (CEA) is the established surgical procedure for stroke prevention in patients with extracranial carotid artery disease (Tables 81.1 and 81.2). Some procedural technical issues continue to be debated, such as the benefi ts of an intraoperative shunt or of a patch closure versus primary

repair. Variability in the reporting of surgical results con-tinue to make interpretation and comparison of studies dif-fi cult. In a meta-analysis of CEA in symptomatic patients (n = 51 studies), the strongest predictor of stroke or death was the type of specialist (neurologist or surgeon) who performed the postoperative assessment.45 When a neurologist evalu-ated postoperative patients, the risk of stroke and death was 7.7% [95% confi dence interval (CI) 5–10.2]; however, when a single-author surgeon performed the evaluation, the risk was reported as 2.3% (95% CI, 1.8–7). The American Heart Asso-ciation (AHA) expert consensus panel suggested that the perioperative risk of stroke and death should not exceed 3% for asymptomatic patients, 6% for symptomatic patients, or 10% for repeat CEA.46

Percutaneous Therapy

Extracranial carotid artery angioplasty and stent placement has evolved over the past 20 years to become an accepted method for treating patients with selected carotid lesions.4,47–49 (Fig. 81.7). Because the extracranial carotid artery is subject to external compression and rotation, self-expanding stents are used to avoid stent deformation. Concern over the potential release of cerebral emboli led to

TABLE 81.1. Symptomatic carotid endarterectomy (CEA) trials: risk of stroke at 3 years

Number Medical CEA needed to Perioperative risk of risk of treat to 30-day stroke stroke prevent 1 stroke andTrial (%) (%) stroke death (%)

NASCET 70–99%62 25.1 8.9 6 5.8NASCET 50–69%63 16.2 11.3 20 7.1ECST 70–99%61 16.8 10.3 15 7.5

NASCET, North American Symptomatic Carotid Endarterectomy Trial; ECST, European Carotid Surgery Trial.

TABLE 81.2. Asymptomatic CEA trials: risk of stroke at 5 years

Number needed to Perioperative Medical CEA risk treat to 30-day risk of of stroke prevent 1 stroke andTrial stroke (%) (%) stroke death (%)

ACAS 60–99%28 11 5.1 67 2.3ACST 60–99%64 11 3.8 NA 3.1

ACAS, Asymptomatic Carotid Atherosclerosis Study; ACST, Asymptomatic Carotid Surgery Trial.

FIGURE 81.7. Left panel: Tight internal carotid stenosis. Right panel: After stent placement.


c a ro t i d a rt e ry i n t e rv e n t ion 1747

were male, 10% were older than 80 years, and 56% were symptomatic. The CAS was technically successful in 98%, with an EPD used in 64%. The combined end point of mor-tality and/or a severe neurologic defi cit occurred in 2.8% of the patients, and was 2.4% in asymptomatic and 3.1% in symptomatic patients. Interestingly, there did not appear to be any difference in outcomes for those treated with or without EPDs (2.2% with EPD and 2.1% without EPD). These data indicate that excellent outcomes can be obtained from carotid stent placement when the procedure moves away from investigational centers and into community hospitals.

Comparative Clinical Trials: Stroke Prevention

Surgery Versus Medical Therapy

The initial surgery versus medical therapy trials compared best medical therapy, aspirin, versus CEA for prevention of stroke and death in symptomatic patients. Both the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) demonstrated that with selected surgeons and patients with carotid stenoses (70–99%) causing hemispheric or ocular symptoms, there was an unequivocal benefi t for CEA over medical therapy for the prevention of stroke (Fig. 81.9).61,62 This benefi t was realized despite a 6% incidence of periopera-tive stroke and death. With more modest severity carotid stenoses (50–69%), the number of patients needed to treat with CEA to prevent one stroke increased to 15.63 In these moderately severe carotid lesions, male patients demon-strated benefi t, while female patients did not.

For asymptomatic carotid lesions, there is good evidence that with appropriate perioperative risk, patients with 60% to 99% lesions will benefi t from CEA compared to medical therapy. In the Asymptomatic Carotid Surgery Trial (ACST), 3120 patients were randomized to medical therapy or CEA with a perioperative stroke and death risk of 3.1%.64 The 5-year risk of stroke was reduced from 11% in the medical group to 3.8% in the CEA group (p < .001) (Fig. 81.10). This slightly exceeded the benefi t seen with the Asymptomatic

TABLE 81.3. Conditions conferring increased risk for carotid artery surgery

Anatomic criteria High cervical or intrathoracic lesion Prior neck surgery or radiation therapy Contralateral carotid artery occlusion Prior ipsilateral CEA Contralateral laryngeal nerve palsy TracheostomaMedical comorbidity Age >80 years Class III/IV congestive heart failure Class III/IV angina pectoris Left main coronary disease Two- or three-vessel coronary artery disease Need for open heart surgery Ejection fraction ≤30% Recent myocardial infarction Severe chronic obstructive lung disease

TABLE 81.4. Increased risk for carotid stent

Tortuous aortic archPlatelet of clotting disorderDiffi cult vascular accessLesion calcifi cationVisible thrombus

the development of emboli protection systems.50 These pro-tection systems fall into three categories: (1) distal balloon occlusion with aspiration,51 (2) proximal occlusion with aspi-ration,52 and (3) distal fi lter systems.53 Currently the fi lter systems are the most user-friendly and appear to be effective. Carotid artery angioplasty with stenting using an emboli protection device has been approved as an alternative to high surgical risk CEA (Tables 81.3 and 81.4),27 but is also being investigated as an alternative for routine CEA patients.54

Several large, nonrandomized, prospective registry studies [e.g., Boston Scientifi c EPI: A Carotid Stenting Trial for High-Risk Surgical Patients (BEACH), ACCULINK for Revascularization of Carotids in High-Risk patients (ARCHeR), and Study to Examine the Cerebral Protection System and X-Act Stent in patients at high risk for Carotid Endarterectomy (SECuRITY)] investigating the safety and effi cacy of CAS with emboli protection in symptomatic and asymptomatic patients at increased risk for surgical treat-ment have recently been completed.55–59 All of these trials have met their targets for safety and effi cacy (Fig. 81.8). A result of the Food and Drug Administration’s (FDA) concern over postapproval safety and widespread distribution of carotid stent therapy is the requirement that patients be enrolled in an industry sponsored, postmarket surveillance (PMS) trial to qualify for Medicare reimbursement.

Germany has approached this issue in a similar way, by establishing a registry open to any investigator in Germany, Austria, or Switzerland who performs CAS.60 A total of 38 centers are participating and have enrolled 3853 cases. Par-ticipants are evenly distributed among interventional angi-ology, cardiology, and radiology. To avoid selection bias, all patients had to be registered prior to the procedure and fol-lowed until hospital discharge or demise. Carotid stent placement was attempted in 3267 patients, of whom 70%

10

8

6

4

2

0

Beach Sapphire ARCHeR-2 SECuRITY

7.8

5.7

7.87.2

Per

cent

FIGURE 81.8. Bar graph of high surgical risk carotid artery stent trials with emboli protection devices showing 30-day stroke and death.56


174 8 c h a p t e r 81

Carotid Atherosclerosis Study (ACAS) in which asymptom-atic patients with 60% to 99% carotid stenoses were random-ized to medical therapy or surgery with an estimated 5-year risk of ipsilateral stroke of 11% compared to only 5.1% in the CEA group.28 This was accomplished with a 30-day stroke and death risk of 2.3%.

Controversy exists over the actual risk of carotid surgery, which may not be refl ected in the highly selected population of patients and surgeons participating in the randomized trials. Wennberg and colleagues65 analyzed mortality results for all Medicare patients (n = 113,300) undergoing carotid endarterectomy during the same period that the randomized surgical versus medical therapy trials were being conducted. They found that the 30-day mortality rate in the Medicare population was three times higher than reported in the ran-domized trials. There was also a strong relationship between increasing age and perioperative mortality, with patients older than 85 being three times more likely to die than those younger than 70. Given the higher mortality results in the Medicare population, which represent a disproportionate number of patients receiving carotid surgery, the authors

argued that the results of carotid surgery in the highly selected patients represented by the randomized trials and performed by highly selected surgeons were not representa-tive of everyday carotid surgery practice.

Surgery Versus Carotid Stent Placement

Percutaneous revascularization with stent placement offers a less invasive alternative to surgery. Stent placement is per-formed without the risk of general anesthesia, offering a lower procedural morbidity and mortality, a shorter hospital stay, and a lower cost. Nonsurgical options become particu-larly attractive in patients with signifi cant medical comor-bidities or other conditions that increase their risk of surgical complications (Table 81.3). However, patient selection for carotid stent placement must also take into account com-plex anatomy that increases the risks for stent placement (Table 81.4).

Two very early randomized trials of CAS (without embolic protection) versus CEA were not encouraging. The fi rst was a stopped trial published by Naylor et al.66 that enrolled only 17 patients. Patients were treated with aspirin only; no emboli protection was used and lesion predilation was not routinely performed. Five of the seven (71%) CAS patients suffered a periprocedural stroke, compared to none of the surgical patients.

The Wallstent trial randomized 290 symptomatic patients with 60% to 99% carotid lesions to either CEA or CAS.67 The stroke and death rate at 1 year was 12.1% for CAS and 3.6% for CEA (p = .022). These trials were both criticized for select-ing inexperienced operators and for not using EPDs. The failure to routinely predilate lesions may have contributed to “snow plowing” across the lesions, thereby releasing emboli, with the relatively large stent catheters and the lack of clopidogrel may have contributed to the increased complications.

The Carotid and Vertebral Artery Transluminal Angio-plasty Study (CAVATAS) was a European multicenter ran-domized trial of carotid balloon angioplasty versus surgery.68 A total of 504 patients (>90% symptomatic) were randomized to CEA (n = 253) or angioplasty (n = 251). Only 26% of the angioplasty patients received a stent for a failed or subopti-mal balloon angioplasty result. The 30-day end point of dis-abling stroke or death showed no difference between the angioplasty arm (10%) or the surgical arm (9.9%). The 95% confi dence intervals for the surgical event rate (6.2–13.6%) overlapped with the complication rates of both the European Carotid Surgery Trial (7.0%, 95% CI 5.8–8.1%) and the North American Symptomatic Carotid Endarterectomy Trial (6.5%, 95% CI 5.2–7.8%) (Fig. 81.11). Complications of cranial nerve injury and myocardial ischemia were seen only in the surgi-cal arm. After 3 years of follow-up, there continues to be no difference for death or disabling stroke, or ipsilateral stroke, between the groups (Fig. 81.12).

The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial compared CAS with distal emboli protection to CEA in patients at increased risk for complications at surgery.27 A total of 747 patients were entered into the trial, with 159 randomized to CAS with distal protection, and 151 randomized to CEA. An additional 406 patients were refused surgery and were treated

MED SURG

30%

25%

20%

15%

10%

5%

0%

26.0%

p <.001 p <.045

p <.001

9.0%

22.2%20.6%

6.8%

15.7%

NASCET ≥70 ECST ≥80NASCET 50–69FIGURE 81.9. Three-year outcome of carotid surgery versus medical therapy.61–63 NASCET, North American Symptomatic Carotid End-arterectomy Trial; ECST, European Carotid Surgery Trial.

Any type of stroke or perioperative death100

95

90

85

0

0 1 2 3 4 5 Years

Difference 5.35% (95% Cl 2.96–7.75)z = 4.38, p <.0001

Eve

nt-f

ree

(%)

Immediate 6.42% (SE 0.70)

Deferred 11.78% (SE 1.00)

FIGURE 81.10. Asymptomatic Carotid Surgery Trial (ACST) results showing benefi t for asymptomatic undergoing immediate versus delayed carotid endarterectomy (CEA).



in a stent registry, while only seven patients were refused CAS and were treated in a surgery registry.

In the randomized patients, the 30-day incidence of stroke/death/myocardial infarction [combined major adverse

event (MAE) end point] was lower for CAS (4.8%) than CEA (9.6%, p = .14). The surgical group also had an excess of cranial nerve injuries (5.3%), which were not seen in the stent group. The 1-year combined end point for the CAS group was 12.2% compared to 20.1% (p = .05) in the CEA group (Table 81.5). This randomized trial provides strong evidence that stent placement with distal protection is the procedure of choice for patients at increased risk for carotid surgery.

Emboli Protection Devices

The Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) trial is an ongoing multicenter, randomized, open-label, assessor-blind, noninferiority study to determine whether CAS (with or without an EPD) is as safe and effective as carotid surgery.69 After 80 patients had been enrolled in the carotid stent arm of the trial, the safety committee recommended stopping “unprotected” CAS due to an excess of strokes (both minor and major) in the relatively small number of patients treated without EPD (Fig. 81.13).

This decision of not allowing CAS without EPD is con-troversial, because (1) the differences between the groups did not reach statistical signifi cance; (2) patients were not ran-domly allocated treatment with an EPD; (3) those without EPD were signifi cantly older (66 vs. 72.7 years, p = .013),

Outcomes for CEA patients (mean, 95% Cl)

6.5 (5.2–7.8)

7.0 (5.8–8.1)

9.9 (6.2–13.6)

NASCET

ECST

CAVATAS

4 5 6 7 8 9 10 11 12 13

Percent

1.00

0.75

0.50

0.25

0

1.00

0.75

0.50

0.25

0

Endovascular treatmentSurgical treatment

0 1 2 3

0 1 2 3

Sur

viva

l pro

babi

lity

Years from randomization

FIGURE 81.11. Comparison of surgical perioperative stroke and death rates for the North American Symptomatic Carotid Endarter-ectomy Trial (NASCET),62 the European Carotid Surgery Trial (ECST),61 and the Carotid and Vertebral Artery Transluminal Angio-plasty Study (CAVATAS).71 The 95% confi dence intervals for the surgical event rate (6.2–13.6%) overlapped with the complication rates of both the ECST (95% CI 5.8–8.1%) and the NASCET (95% CI 5.2–7.8%).

FIGURE 81.12. Kaplan-Meier survival curves from CAVATAS (71). The upper graphic shows death and disabling stroke in any vascular territory, and the lower graph shows ipsilateral stroke lasting more than 7 days.

TABLE 81.5. One-year outcome for the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) (intention to treat)27

Group Death (%) Stroke (%) MI (%) Combined (%)

CAS 7.4 6.2 3.0 12.2CEA 13.5 7.9 7.5 20.2*

CAS, carotid artery stent; CEA, carotid endarterectomy; MI, myocardial infarction.

CAS + EPD CAD – EPD

30

25

20

15

10

5

0

13.3

1.7

10.3Per

cent

Major stroke Stroke and death Procedure stroke

5.2

13.3

p = ns for all26.7

FIGURE 81.13. Comparison of carotid stent placement (CAS) with and without an emboli protection device (EPD) in the Endarterec-tomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) trial. Although there was an excess of adverse events in the group without distal protection, it did not reach statistical signifi cance.69


175 0 c h a p t e r 81

which is a known risk factor for stroke with CAS; and (4) lesion predilation was performed three times more often in the group with EPD, which may have lowered the risk of procedural stroke.70 Remembering that EPDs can only reduce embolic strokes during the procedure, it is interesting to note that only two strokes occurred on the day of the procedure in the group treated without an EPD compared to three strokes in the group treated with an EPD, a difference that may have arisen by chance.

The use of EPDs is likely to decrease cerebral emboli during the procedure, at a potential cost of increasing the complexity of the procedure with an increase in complica-tions directly related to the EPD. In the CAVATAS trial,71 the 30-day stroke rate without EPD was 10%, which is not dif-ferent from the 10.3% reported for EVA-3S.69 There remains no conclusive evidence that the use of EPDs reduces the risk of stroke, and the need for a randomized trial is becoming clear.

Carotid Stent Guidelines

Training and Credentialing

There are two pathways for physician training for this pro-cedure as addressed in a multisocietal consensus document, which specifi es criteria for cardiologists, radiologists, and surgeons achieving competency in noncoronary endovascu-lar procedures.72 The “practice pathway,” which expires 5-years following the publication of the document, is for use by physicians not in training programs, while the “training pathway” is for those in formal Accreditation Council for Graduate Medical Education (ACGME) accredited residency and fellowship training programs.

The document clearly details the method of counting procedures in an attempt to exclude those participating in “outlaw” programs that offer an excessive number of vessels treated per patient during a weekend course. This document is a consensus statement representing multiple stakeholder specialties, recognizing their different training backgrounds, with recommendations for achieving competence in vascu-lar medicine and noncardiac vascular intervention. For car-diologists-in-training, this document cites Core Cardiology Training II (COCATS-II) as the foundation for cardiology fellowship training in peripheral vascular medicine and intervention.73

A more specifi c document related to the performance of carotid intervention was recently published and endorsed by vascular medicine, vascular surgery, and cardiology organizations.74 This document outlines the three major ele-ments of competency: (1) cognitive (Table 81.6), (2) technical (Table 81.7), and (3) clinical skills (Table 81.8). The document recognizes that cardiology, vascular surgery, and radiology should all have an equal opportunity to be involved in this fi eld, but they have very different training backgrounds and different skill sets. For example, a cardiologist who has performed thousands of coronary angiograms and hundreds of coronary angioplasty procedures will quickly gain tech-nical competence, but there is a need for a formal didactic training program to address any gaps in the fund of knowl-edge regarding carotid artery disease. The surgeon, on the

other hand, may possess a very deep understanding of carotid artery disease, but may have little or no experience performing angiography. Clearly, training programs for carotid intervention must recognize these strengths and weaknesses.

TABLE 81.6. Cognitive requirements for performance of carotid stenting74

I. Atherogenesis (including risk factors) II. Pathophysiology of carotid disease III. Natural history of carotid disease IV. Pharmacotherapy (antiplatelet agents, lipid-lowering agents) V. Associated pathology (e.g., coronary and peripheral artery

disease) VI. Diagnosis: a. History and physical examination b. Noninvasive imaging i. Duplex ultrasound ii. MRA iii. CTA VII. Angiographic anatomy (arch, extracranial, intracranial,

basic collateral circulation, common anatomic variants, and non-atherogenic pathologic processes)

VIII. Case selection: a. Knowledge of alternative treatment options for carotid

stenosis b. Indications and contraindications for revascularization

to prevent stroke c. High-risk carotid endarterectomy criteria d. High risk percutaneous interventional criteria

TABLE 81.7. Technical requirements for performance of carotid stenting74

I. Antiplatelet therapy and procedural anticoagulation II. Angiographic skills i. Vascular access skills ii. Angiographic catheter selection iii. Knowledge of angiographic anatomy including the circle

of Willis and common variants iv. Familiarity with use of angulated views and appropriate

movement of the x-ray gantry III. Interventional skills i. Guide catheter/sheath placement ii. Deployment and retrieval of embolic protection device iii. Pre- and postdilation iv. Stent positioning and deployment IV. Recognition and management of intraprocedural

complications i. Cerebrovascular events ii. Stroke or cerebrovascular ischemia iii. Embolization iv. Hemorrhage v. Thrombosis vi. Dissection vii. Seizure and loss of consciousness V. Cardiovascular events i. Arrhythmias ii. Hypotension iii. Hypertension iv. Myocardial ischemia VI. Vascular access events i. Bleeding ii. Ischemia iii. ThrombosisVII. Management of vascular access with closure devices


c a ro t i d a rt e ry i n t e rv e n t ion 1751

The Author’s Use of This Information in Clinical Practice

The current approach to carotid artery stenting is limited primarily by a 10-year-old national noncoverage decision by the Center for Medicare and Medicaid Services (CMS) that stipulated that Medicare will not reimburse physicians or hospitals for carotid, vertebral, or cerebral angioplasty (Fig. 81.14). The rationale for this decision, which has no precedent in cardiovascular medicine, is unclear and unjustifi ed. This reimbursement decision meant that if any patient received angioplasty or stent placement of a carotid, vertebral, or cerebral vessel, then the entire hospitalization was a noncov-ered service and would not be reimbursed.

In 2001, CMS revised this decision to allow payment for carotid stents done under the auspices of FDA-approved clini-cal trials. This restricted the availability of carotid stents to patients who were candidates for Investigational Device Exemption (IDE) trials. Patients who desperately required carotid revascularization and were not candidates for surgical therapy still could not be offered carotid stent placement

unless they met enrollment criteria for the trial. Patients with atrial fi brillation, for example, were routinely excluded from the clinical trials, and therefore Medicare would not reim-burse hospitals or physicians for carotid stent placement.

Following FDA approval of a carotid stent system (Guidant, Santa Clara, CA), CMS, in October 2004, revised its payment criteria to include patients enrolled in post–market surveillance trials approved by the FDA. In addition to the published clinical trials, in March 2005, CMS disre-garded published clinical trial evidence supporting a much broader application of this technology, and agreed to reim-burse for carotid stent placement only in symptomatic patients at high risk for CEA who have a 70% or greater stenosis.

Current practice is therefore limited to (1) FDA-approved preclinical trials, (2) FDA-approved post–market surveillance trials, and (3) routine clinical use for symptomatic high sur-gical risk patients with ≥70% stenoses. Unfortunately, this strategy will minimize costs to the government at the expense of preventing dissemination of this technology to clinicians.

The evidence from the single randomized trial and mul-tiple registry trials is that CAS with emboli protection is preferred over CEA in high surgical risk symptomatic and asymptomatic patients with suitable aortic arch anatomy. Currently, patients who do not meet high surgical risk crite-ria should be offered surgery.75 Trials are continuing for low-surgical risk patients, and very likely will show that CAS is at least equivalent to CEA without the surgical morbidity.

Summary

Atherosclerotic carotid artery disease is a major contributor to the incidence of stroke, particularly in the elderly. Athero-sclerosis is a systemic illness and patients often present with multisystem involvement of several vascular beds including coronary, cerebral, and peripheral vascular territories. The majority of strokes related to carotid artery disease are embolic in nature, not occlusive. Noninvasive screening tests including ultrasound, CTA, and MRA are helpful in identify-ing pathology. However, the gold standard for diagnosis and treatment allocation remains invasive angiography.

Medical therapy to reduce the risk of stroke includes antiplatelet agents, primarily aspirin in doses of 81 to 325 mg per day. Control of blood pressure and the use of statin therapy is effective in reducing the incidence of stroke. Carotid endarterectomy is more effective than aspirin therapy for preventing stroke in symptomatic (TIA or stroke) patients with ≥50% diameter stenosis and asymptomatic patients with ≥60% diameter stenosis. In patients at increased risk for surgical complications during stroke prevention surgery (carotid endarterectomy), carotid stents have been shown to be as good as or better than surgery at improving outcomes.75

References

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TABLE 81.8. Clinical requirements for performance of carotid stenting74

I. Determine the patient’s risk/benefi t for the procedure II. Outpatient responsibilities a. Preprocedure medications b. Patient and family counseling III. Inpatient responsibilities a. Admitting privileges and order writing. b. Obtain informed consent for procedures. c. Provide pre and post-procedure hospital care i. Neurologic evaluation pre and post procedure ii. Postprocedure pharmacotherapy iii. Monitoring of hemodynamic and cardiac rhythm status IV. Participate in poststent surveillance and clinical outpatient

follow-up visits

Patient at highrisk for CEA

Suitableanatomyfor CAS

Eligible for FDAtrials

(IDE or PMS)

Enroll in trialCMS reimbursed

CAS

CEA

Enroll in lowsurgical risk

CAS vs CEA trial

Candidate for carotidrevascularization for stroke prevention

1. High-risk CEA2. Medical therapy

1. Self-pay for CAS procedure2. Third-party payer for CAS3. High-risk CEA4. Medical therapy

Symptomatic≥70%

stenosis

CMS reimbursedCAS

YesYes

Yes

Yes

NoNo

No

No

FIGURE 81.14. Algorithm for carotid stent use.


1752 c h a p t e r 81

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