A Multispecialty Consensus-Based Approach to Carotid Artery Revascularization is Feasible in Routine Clinical Practice and Results in Excellent Clinical Outcomes

Abstract: Background. Carotid artery stenting (CAS) and endarterectomy (CEA) are considered competing rather than complementary carotid artery revascularization (CAR) strategies. However, patient characteristics that increase procedural risk are quite different for CAS or CEA. We hypothesized that selecting a CAR strategy based on individual patient characteristics using a multispecialty consensus based (MSCB) approach will result in superior outcomes in the overall CAR group. We evaluated the feasibility of an MSCB approach to CAR in routine clinical practice. Methods. We performed a retrospective review of patients undergoing CEA or CAS at the Kansas City Veterans hospital over a 2-year period. As routine clinical practice, each case was discussed in a weekly “vascular conference” by vascular surgery, radiology, and interventional cardiology physicians and a revascularization strategy was chosen. Thirty-day and 1-year incidences of stroke, transient ischemic attack, myocardial infarction, and death were recorded. Results. Eighty CAR procedures were performed (45 CEAs and 35 CASs). The CAS group had an average of 1.9 surgical high-risk features, while the CEA group had 0.5 (P<.05). The CAS group had significantly more common carotid stenosis, stenoses considered too high or low for CEA, and more long internal carotid artery lesions. For the overall CAR group, 30-day incidence of stroke/transient ischemic attack, myocardial infarction, and death was 2.5% and 1-year incidence of stroke and death was 5%. Conclusion. An MSCB approach allows the choice of an optimal CAR strategy with excellent clinical outcomes. Reporting outcomes for the overall CAR may be a better way of assessing and comparing outcomes of CAR across health-care systems rather than CEA or CAS outcomes separately. 

J INVASIVE CARDIOL 2014;26(3):123-127

Key words: carotid artery disease, carotid artery stenosis, carotid endarterectomy, carotid stenting

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Extracranial carotid artery disease is one of the leading causes of ischemic stroke in the United States (US). Several landmark clinical trials conclusively showed that for both symptomatic (>50% diameter stenosis) and asymptomatic (>70% diameter stenosis) carotid artery stenosis, surgical revascularization is superior to medical management alone.^1-4

These studies resulted in a remarkable rise in the number of carotid endarterectomy (CEA) procedures performed across the US. However, after several years of data from registries and Medicare databases were analyzed, it became apparent that the results of even carefully controlled clinical trials could not be extrapolated to a broader patient population in routine clinical practice.⁵ In the NASCET trial, patients with high-risk characteristics such as age greater than 79 years, organ failure of kidney, liver, heart, or lung, those with a cardiac valvular disease, or those with prior ipsilateral CEA were excluded. Additionally, these patients were deemed temporarily ineligible if they had uncontrolled hypertension or diabetes, unstable angina or recent myocardial infarction, progressive neurologic signs, contralateral CEA within 4 months, and any major surgery within the past 30 days.⁶ Therefore, it is hard to generalize these results to a general patient population. 

In this same time period, less invasive percutaneous techniques (angioplasty and stenting) became available. These techniques offered an alternative approach to treating extracranial carotid stenosis. The last several years have seen the publication of numerous clinical studies that have compared carotid artery stenting (CAS) with CEA.^7-14 Most of these studies were done in patients traditionally considered high risk for CEA. Some of these high-risk characteristics included age greater than 80 years, congestive heart failure or severe left ventricular dysfunction, recent myocardial infarction, unstable angina, severe pulmonary disease, contralateral carotid occlusion, contralateral laryngeal nerve palsy, radiation therapy of the neck, radical neck surgery, and previous CEA with recurrent stenosis.⁷

This led the US Food and Drug Administration (FDA) to approve CAS (in 2004) for patients traditionally considered high risk for CEA. More recently, the large National Institutes of Health (NIH)-supported CREST (Carotid Revascularization Endarterectomy vs Stenting Trial) study showed that the risk of composite primary outcome of stroke, myocardial infarction, or death did not differ significantly between CAS and CEA.¹¹ This resulted in the expanded approval of CAS for standard-risk patients by the FDA in May of 2011. 

These studies have led to a remarkable debate between various clinical specialties regarding the best revascularization strategy for these patients. Because of conflicting study results and their even more divergent interpretation, very often due to differing specialties of physicians caring for patients with carotid artery disease, no consensus has emerged.^15-18 In fact, most of this debate has been focused on proving if one modality is superior or equivalent to the other and these techniques have been portrayed as universally competing (rather than complementary) for patients needing carotid artery revascularization. There are scant data looking at these as complementary techniques rather that competing ones. Each technique has differing strengths and limitations and there is some evidence that there are individual patient subsets where one technique may be superior to the other.^19-21 Thus, an ideal strategy would be to choose revascularization strategies based on individual patient characteristics (clinical and anatomical). Such a strategy would examine the complementary roles of CAS and CEA in carotid revascularization and one could then look at the overall outcomes in this “carotid revascularization” (CAR) group as a whole rather than CAS or CEA in isolation. 

There is scant information available regarding the clinical outcomes if patients are treated with a multispecialty team approach in routine clinical practice outside the purview of carefully controlled trials. We hypothesized that a combined multispecialty approach to the management of patients with extracranial carotid artery disease is feasible in routine clinical practice and results in excellent overall revascularization outcomes, since strategies are chosen based on individual patient characteristics with less specialty bias.

Methods

This is a retrospective observational study. All required approvals were obtained from the Kansas City Veterans Administration (KCVA) Medical Center institutional review board and human subjects committee. We conducted a retrospective chart review of all patients who underwent CEA or CAS at the KCVA Medical Center from July 1, 2006 through March 31, 2008. During this time, we instituted as routine clinical practice a multispecialty approach for the management of patients with extracranial carotid artery disease. Each case was discussed in a weekly “vascular conference,” where there was equal participation from vascular surgery and endovascular specialists (interventional radiology and cardiology). The group comprised two vascular surgeons, two interventional radiologists, and one interventional cardiologist. Clinical and radiological data were evaluated and the revascularization strategy was chosen based on clinical and anatomic factors as determined by the participating physicians. There were no predetermined defining variables that mandated the choice of a particular revascularization strategy. In general, CEA was chosen if the surgeons felt that the case was quite low risk and stenting was chosen if the interventionalists thought the risk for CAS was low. In cases where there was consensus that either strategy would be appropriate, treatment was left to the choice of the primary treating specialist for the patient. Vascular surgery was the primary team on all except 10 patients.

The study subjects were identified from the electronic medical records using relevant diagnostic codes. Clinical and laboratory data were collected by electronic retrieval and manual chart review. 

Several data points were collected, including demographic, clinical, and radiographic/angiographic characteristics. Patient data points, including age, gender, race, weight, height, serum creatinine, and estimated glomerular filtration rate were collected. Additionally, past medical history of stroke or transient ischemic attack, history of ipsilateral CEA, history of neck radiation, history of neck surgery/dissection, history of recurrent laryngeal nerve palsy, history of coronary artery disease (CAD), and other clinical risk factors considered high risk for CEA (ie, severe chronic obstructive pulmonary disease [COPD]) were recorded. Angiographic data points included lesion location, presence of tandem lesions or lesions more than 2 cm in length, vessel diameter, severity of stenosis, “string sign,” brisk vs sluggish flow, contralateral stenosis, high bifurcation, moderate to severe calcification, and presence of thrombus. For study purposes, angiographic images were reviewed retrospectively by two of the investigators (KG, BN) independently and any differences were reconciled by mutual agreement. 

The incidence of composite endpoint of stroke, transient ischemic attack, myocardial infarction, and death was recorded at 30 days. We also assessed incidence of any stroke and death at 12 months after revascularization. Stroke was defined as any focal irreversible neurological deficit occurring following the procedure. This diagnosis was derived from direct chart review. Myocardial diagnosis was also derived from the patient’s records and included both non-ST elevation and ST-elevation myocardial infarction.

Statistical analysis. Standard statistical tools were utilized. SPSS and STATA version 9.0 were used to analyze the data. Continuous data were described as the mean ± standard deviation, and categoric data were described as frequencies. The association between a clinical event/endpoint and specific clinical and laboratory variables was evaluated using the t-test for continuous variables or the Fischer’s exact test for categoric variables. A P<.05 was considered statistically significant. Bivariate and multivariate analyses were conducted to examine the study objectives. Variables significant in the bivariate analysis were included in the multivariate analysis.

Results

Over the course of nearly two years, there were 80 carotid revascularization procedures done on 76 patients (45 CEAs and 35 CASs). All CAS procedures were performed with use of a distal embolic protection device. The mean age was 67 ± 9 years with mean diameter stenosis of 80 ± 15%. Of these patients, 39% had symptomatic carotid artery disease. In the CAS group, 40% were symptomatic, whereas 33% of the CEA group were symptomatic.

Additional baseline clinical characteristics of the study groups are detailed in Table 1. There were significantly more patients with ischemia on thallium imaging in the stenting group (P<.05).

Clinical and anatomic factors that are traditionally thought to indicate high risk for CEA were evaluated. These variables included age >80 years, prior ipsilateral CEA, congestive heart failure (ejection fraction [EF] <40%), prior neck surgery, awaiting coronary artery bypass grafting, high lesion, contralateral occlusion >80%, history of neck radiation, laryngeal nerve palsy, and presence of low lesions (ostial, proximal, or mid common carotid artery (CCA) and those considered to be inaccessible surgically via a simple cervical approach). These features are listed in Table 2. The CAS group had an average of 1.9 surgical high-risk features, while the CEA group had only 0.5 (P<.05). We also reviewed specific angiographic features that are considered high risk for stenting, including tandem lesion or lesion length greater than 2 cm, string sign, heavy calcification, slow flow, presence of thrombus, or cerebral circulation filling from contralateral circulation. These variables are listed in Table 3 and marked with an asterisk. There were significantly more patients with CCA stenosis, stenosis considered too high or low with respect to the mandible and clavicle, respectively, in the CAS group, as were long internal carotid artery (ICA) lesions. There was a trend toward more patients with severe calcific lesions and string sign in the CEA group, but this did not reach significance (likely due to the small study population).

The 30-day composite endpoint of stroke, transient ischemic attack, myocardial infarction, and death was 2.5% for the entire revascularization group. There was 1 non-fatal non-ST elevation myocardial infarction in the CAS group and 1 non-fatal, non-disabling stroke in the CEA group. The 1-year incidence of major stroke and death was 5%, with 2 non-vascular deaths in each group. 

Discussion

Several randomized and non-randomized studies have compared CAS to CEA in both symptomatic and asymptomatic patients.^{7,8,10,11,22,23} These studies have included patient subsets considered to be both high risk for CEA and those considered to be standard risk. The results have not been uniformly consistent, but have established CAS as an accepted revascularization modality for carotid disease. However, these randomized studies mostly included patients thought to be suitable for both CAS and CEA. Thus, they looked at these revascularization strategies as competing and not necessarily complementary techniques. 

Most recently, the CREST study found that there was no difference in the primary outcome of stroke, myocardial infarction, or death between the CAS with distal embolic protection and CEA groups. This study randomized 2522 patients with 1251 patients in the CEA group and 1271 patients in the CAS group. Eighty-seven percent of patients had >75% stenosis and 47% of patients were asymptomatic. The incidence of the primary outcome was similar in the two groups. However, there was an increased risk of periprocedural stroke (4.1% for the CAS group and 2.3% for the CEA group; P=.01) in the CAS group and myocardial infarction (1.1% for the CAS group and 2.3% in the CEA group; P=.03) in the CEA group.¹¹ Since CREST was a randomized study, it enrolled patients who were considered suitable for both procedures. Thus, it excluded patients who the operators thought were not suitable candidates for either procedure.

The CREST study results did identify certain subgroups that did better with one or the other revascularization technique. For instance, younger patients had a slightly better outcome with CAS and older patients had better outcomes with CEA.¹¹ Similar findings regarding age were also seen in the SPACE trial.¹⁰

CAS and CEA as revascularization techniques are quite different and each procedure appears to have its own set of high-risk patient subsets.¹⁹ Patients that are at high risk for CEA are not necessarily low risk for stenting. Thus, just because a patient is high risk for surgery, does not make him a good CAS candidate. In fact, he could be even higher risk for stenting or could be an excellent CAS candidate. Similarly, patients who are low risk for CEA may also be excellent candidates for stenting and vice versa. 

Table 2 lists characteristics that are considered to confer a higher risk for CEA. Likewise, there is increasing recognition that there is a different set of characteristics that make patients high risk for CAS. Table 3 lists some of these angiographic variables. One of the traditional high-risk factors for CEA has been considered to be age >80 years.²⁴ Thus, these patients were considered better candidates for CAS. However, elderly patients also have several features that are considered “high risk” for CAS, such as type III aortic arch, tortuous and calcific carotids, contralateral occlusions, and large atheroma burden in the arch.^24-28 In fact, several studies have shown that stroke risk is several-fold higher in octogenarians undergoing stenting.^24,25

However, age may not be an adverse variable in itself. Chiam et al demonstrated that CAS could be performed safely in octogenarians if their vascular anatomy was suitable.²² They described high-risk features that should be avoided, including excessive vascular tortuosity, heavy concentric calcification of the lesion, and decreased cerebral reserve, defined as prior large stroke, multiple lacunar infarcts, intracranial micro-angiopathy, or dementia. When avoiding these high-risk features, the overall 30-day stroke or death rate was 5.1% in symptomatic patients and 2.6% in asymptomatic patients. These results are similar to comparable studies of CEA in elderly patients. Thus, the authors make a case that it is not just the age but rather presence of certain angiographic and other variables that increase the risk of CAS in octogenarians.

Few published studies have allowed allocation of revascularization strategies based on physician assessment of patient characteristics (clinical and angiographic), which may favor one modality over the other. The CaRESS study was one such investigation that allowed physicians to choose the best revascularization strategy without randomization.¹³ CaRESS was a prospective non-randomized trial to determine whether CAS was equivalent to CEA in a broad patient population considered representative of patients across the US, enrolling both symptomatic and asymptomatic patients and following them for 4 years. Fourteen centers in the US enrolled 439 patients, with 397 actually undergoing CAR. Of these, a total of 254 patients underwent CEA and 143 patients underwent CAS. Baseline demographics and lesion characteristics were not different between the two groups. Baseline clinical characteristics were also similar, although there was a higher rate of history of prior CEA in the CAS group. More than 90% of patients had >75% stenosis and 68% of patients were asymptomatic. This study showed that the risk of death or non-fatal stroke at 30 days, 1 year, and 4 years following CAS with distal protection was equivalent to CEA. The incidence of any stroke at 4 years was 9.6% for CEA and 8.6% for CAS. The composite endpoint of death, non-fatal stroke, and myocardial infarction at 4 years was 27.0% in CEA vs 21.7% in CAS patients. This study suggested that CAS with distal protection was equivalent to CEA.^12,13,29 The study did not look at specific angiographic variables that are considered high risk for stenting.

More recently, Werner et al described anatomic variables that conferred a higher risk during CAS in their large single-center experience.²¹ They identified excessive carotid tortuosity, adverse ICA angulation, and a bovine arch as some of these factors. Severe calcification was found to be associated with increased risk in this study. A recent report from the NCDR CARE registry evaluated several clinical and angiographic variables in order to develop a risk score in order to predict risk associated with CAS.²⁰ They identified age, prior stroke, atrial fibrillation, and absence of prior ipsilateral CEA as some of the clinical factors that increased risk of stroke during CEA. The study did not find an increase in stroke risk with any angiographic factor such as type III arch, lesion ulceration, calcification, thrombus, or lesion length. This finding, although surprising, may be explained by selection bias in this registry, since the physicians likely did not perform CAS in patients with adverse anatomy.

Our study evaluated a multispecialty consensus approach that assessed each patient individually, not just based on if they were surgically high risk, but also if they were higher risk for stenting, and then chose the appropriate strategy. This was done prospectively as a routine clinical practice strategy in order to optimize outcomes for the overall group of patients needing carotid revascularization. The study included all comers, and no patients were excluded. Thus, the study is representative of a real-world patient population. There were no preset guidelines or preidentified criterion that decided the revascularization strategy. Rather than looking individually at outcomes for CAS or CEA groups, we assessed outcomes of the overall revascularization group for the KCVA Medical Center. The study found that characteristics traditionally considered high risk for CEA were significantly more prevalent in the CAS arm than in the CEA arm, while the features considered to confer higher risk during CAS tended to be more prevalent in the CEA arm (though due to small numbers did not meet criterion for statistical significance). Our combined 30-day composite endpoint of stroke, myocardial infarction, and death was 2.5%, which is comparable to the CaRESS data (3.1% for CEA and 2.1% for CAS) and the CREST data (4.5% for CEA and 5.2% for CAS).^12,13,29 Additionally, our combined 1-year incidence of major stroke or death was 5% (CREST data, 14.3% for CEA and 10.9% for CAS).¹¹ We believe that this study sets the stage for a larger study of this multispecialty-based approach toward carotid revascularization. 

We do believe that reporting overall carotid revascularization outcomes (combining the results of both CAS and CEA) is a better method of assessing outcomes for health-care systems and in the long run better serves both the patients and the field of vascular medicine and surgery.

Study limitations. This is a retrospective study and thus subject to the usual limitations of selection bias and unknown confounding variables. The number of patients is modest. All angiographic variables that have been thought to be associated with higher risk with CAS, such as type of arch or arch atheroma, were not assessed. 

Conclusion

Both CAS and CEA are complementary (rather than competing) revascularization strategies for carotid artery stenosis. There are unique patient characteristics (clinical and angiographic) that increase the risk of stroke and other complications with either technique. Several of these characteristics differ for CEA and CAS and it is prudent to choose the revascularization strategy for each patient based on this risk assessment. A combined multispecialty approach allows the choice of the optimal strategy for individual patients. Assessing outcomes for the combined carotid revascularization group (CAS and CEA together) is a better measure than comparing outcomes of carotid revascularization across health-care systems rather than only looking at CEA or CAS individually.

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