Operator Experience Versus Embolic Protection in the Carotid Arteries
A review of the data regarding the theoretical advantages of embolic protection devices over unprotected CAS procedures.
More than 10 years have passed since carotid artery angioplasty and stenting (CAS) surfaced as a potential alternative to carotid endarterectomy (CEA). The controversy over this procedure continues, and we are still trying to figure out which method of treatment is best suited for our patients with obstructive atherosclerosis in the carotid arteries. Furthermore, consensus regarding which patients to treat with either procedure versus best medical therapy continues to be a problem; this is especially true in asymptomatic patients and, frequently, treatment is based on the local standard of care.
In general, stenosis exceeding 70% is considered for either CEA or CAS, with or without symptoms; however, this is a nonhomogenous group due to other risk factors including, but not limited to, atherosclerosis in other vascular territories. The presence of untreated or previously undiagnosed coronary artery disease needs to be considered in every case because the presence of carotid occlusive disease has a high correlation with coronary artery disease. It is not well understood why the opposite is not always true (ie, patients who have coronary artery disease do not always have carotid atherosclerosis).
When considering which patients are at risk for stroke from a high-grade carotid lesion, other issues, including current risk factors (eg, smoking, uncontrolled hypertension, diabetes mellitus, lipid status), must be taken into account. Various methods have been used to predict which lesions represent vulnerability, including conventional angiography, duplex ultrasound, MRA, and CTA. Although the modality most often used to assess these patients is duplex ultrasound, some surgeons perform CEA on the basis of this test alone. Others have argued that a more complete angiographic assessment is mandatory because the carotid duplex examination is only capable of evaluating the extracranial portions of the carotid arteries and assessing vertebral artery flow. Therefore, a tandem stenosis (ie, intracranial narrowing that portends a worse prognosis) or an intracranial aneurysm, arteriovenous malformation, or other vascular pathology may be missed if only a carotid duplex examination is utilized. Although traditional angiography is beginning to take a backseat due to the risk of the diagnostic study (albeit small) versus CTA or MRA, these technologies have surfaced as very accurate tools in making the diagnosis.
The question remains: Which patients should be treated with intervention and which patients should be treated with medical therapy? In the asymptomatic patient, this question remains unanswered, although few would disagree that maximum medical therapy requires risk factor modification, antiplatelet medication, and statin therapy, and should be the first step in convincing the patient to do everything that is possible to prevent a cardiovascular demise. Because many of these risk factors contribute to a pathologic milieu, it is critical that we emphasize that the patient must take ownership of the diagnosis and commit to our recommendations to optimize outcomes and decrease the likelihood of disease progression in other vascular territories.
Among these recommendations, dietary intervention with proper nutritional intake, physical exertion (ie, exercise tailored to the individual's lifestyle and physical capability), and appropriate pharmacologic treatment all represent key elements in future disease progression and cannot be ignored. This is true for both asymptomatic and symptomatic patients. As vascular experts, we should not assume that it is the task of primary care physicians to teach this to the patient. Thus, when we assume the responsibility for carotid intervention, we also need to assume the responsibility to emphasize to the patient all of the issues that will prevent disease progression.
WHAT ABOUT CAROTID PROTECTION DEVICES AND OPERATOR EXPERIENCE?
In 1996, Theron1 reported 259 cases of CAS. The majority of CAS procedures were for atherosclerotic stenosis (188 of 229 patients), whereas 71 cases were for either recurrent stenosis after CEA or arteritis (n=20). No complications occurred in the latter group, whereas 8% (three of 38 patients) who were treated without cerebral protection experienced acute neurologic events. One hundred fifty patients in the atherosclerosis group were treated with carotid protection, and none had a neurologic complication. The protection system used was a triple coaxial catheter system that, by today's standards, is quite complex. Theron concluded that cerebral protection is mandatory to prevent the occurrence of stroke in patients with carotid bifurcation disease.
Data presented at the American College of Cardiology 55th Annual Scientific Session (March 11-14, 2006) suggest that interventionists from a variety of disciplines can effectively achieve excellent results from CAS after completing a formalized training program. Theodore L. Schreiber, MD, presented data from Carotid Artery Stenting with Embolic Protection Surveillance–Post Marketing Study (CASES-PMS) funded and processed by Cordis Corporation (a Johnson & Johnson company, Miami, FL). The purpose of the CASES-PMS study was to demonstrate that outcomes in a periapproval setting, including use of a detailed training program in CAS for physicians not experienced in CAS, allows outcomes that are similar to those obtained in the pivotal trial setting. The study findings both corroborate the findings in the SAPPHIRE study and demonstrate that experienced interventionists from multiple disciplines can perform CAS with results equal to that of the experts who performed the initial clinical trials after a comprehensive training program. The elements of this begin in 2004 and included didactic review, simulation training with case observations, and hands-on experience at the CASES regional education centers across the country.
The preliminary results showed that high-risk surgical patients treated with CAS had a 30-day major adverse event (MAE) rate of 4.8% (62 of 1,279 patients) compared to 4.8% (eight of 167 patients) of CAS patients treated in the randomized arm of the SAPPHIRE trial. The 30-day MAE included all deaths, myocardial infarction (MI), and stroke from 70 sites in the US. Assessment by neurologic examination and an evaluation of adverse events will be reported at 1 year.
William A. Gray, MD, presented Guidant's Carotid Acculink/Accunet Post Approval Trial to Uncover Unanticipated or Rare Events Registry (CAPTURE 3000) at the American College of Cardiology 55th Annual Scientific Session (March 11-14, 2006). The CAPTURE registry entered 3,000 patients treated by 240 interventionists at 118 centers in the US, as required by the FDA postapproval study of the Rx Acculink Carotid Stent System and Rx Accunet embolic protection system (Guidant Corporation, Indianapolis, IN). The goal of the study was to evaluate rare or unanticipated events among patients treated with this system. The report by Gray included the first 2,500 patients in the registry. Of these, 9.3% (232 of 2,500) were symptomatic. Seventy-one percent of the physicians had performed at least 10 CAS procedures as the primary operator. At 30 days, death, stroke, or MI had occurred in 5.7% of patients (death, 1.6%; stroke, 4.2%; MI, 0.9%).
Among those who were symptomatic (233 of 2,500 patients) the composite event rate was 14.2% (death, 4.35; stroke, 11.2%; MI, 2.6%). In patients older than 80 years, the event rates were higher at 8.2% (death, 2%; stroke, 6.2%; MI, 0.5%) when asymptomatic patients were treated.
On March 17, 2006, Guidant began CAPTURE 2, a postapproval study looking at CAS with the Accunet/Acculink systems in high surgical risk patients. The CAPTURE study will enroll 10,000 patients at 400 US centers with the intent to provide additional or more extensive data to extend Medicare coverage of CAS to a broader group of patients.
Shawl2 reported a series of 299 consecutive patients who underwent CAS in 343 extracranial arteries. This series of very high-risk patients included those with unstable angina, previous ipsilateral CEA, contralateral occlusion, and other severe comorbid illnesses. Twenty-five percent (74 of 299 patients) were older than 80 years. Thirty-day assessments yielded 0.6% major (two of 343) strokes and 2.3% minor (seven of 343) strokes. There were no myocardial infarctions or deaths. All of these patients had neurologic evaluations at baseline and 24 hours after the procedure. At a mean follow-up of 26 months (±13 months), 2.7% (eight of 343) of the patients had recurrent asymptomatic restenosis requiring repeat angioplasty. Thirteen percent (39 of 299) of these patients died in this period, none from a neurologic cause. Twenty-four percent (73 of 299) had a coronary intervention during the index admission, reflecting the high-risk status of these individuals. The mean length of stay after CAS was 1.76 days. Existing data suggest that combined or staged CEA and coronary artery bypass surgery (CABG) is associated with stroke rates of 4.5% to 7.1%, and mortality rates of 5.5%.3 Roubin et al4 reported similar success rates in 525 patients who were at high risk, with a major stroke rate of 1% and a minor stroke rate of 4.8% at 30 days. The 30-day, nonstroke mortality rate was 1%, while the risk of fatal stroke was 0.6%. Interestingly, neither of these series had the "advantage" of a carotid protection system.
Evidence to suggest that embolic protection is required, as suggested by Theron,1 is very compelling. Ohki and Marin5 devised a very elaborate ex vivo model using human carotid bifurcation plaques. Their study demonstrated that embolic particles were consistently produced from all plaques that were stented. Both microparticles and macroparticles were obtained using a filter size of 130 µm.
Jaeger and Mathias6 used diffusion-weighted magnetic resonance imaging (DW-MRI) to study the incidence of silent embolic infarct after CAS with images before and after the procedure in 67 patients. New embolic ipsilateral infarctions were demonstrated after stent implants in 29% (20 of 67) of the patients.
Gaunt and Martin7 reported the clinical relevance of microembolization using transcranial Doppler in 100 consecutive patients undergoing CEA. Ninety-two percent of these patients had evidence of embolization, and those with more than 10 emboli during CEA had significant deterioration in cognitive function. Overall incidence of deterioration was 37%, despite the fact that no obvious clinical signs of stroke were present.
Conflicting data by Yadav and Roubin8 suggest that cognitive function may actually improve after CAS and support the notion of hibernation of brain tissue analogous to the concept of hibernating myocardium.9 The experience of Shawl2 showed similar improvement based upon improved stroke scale after CAS in two patients with contralateral occlusions.
CONCLUSIONS REGARDING CAROTID EMBOLIC PROTECTION DEVICES
Current data suggest that embolic protection devices offer considerable theoretical advantages over unprotected CAS procedures. In fact, the current standard of therapy requires their use unless the operator determines that the risk of device deployment exceeds that of performing the procedure without it. In some cases, the severity of the stenosis requires predilation to permit the crossing profile of the device to be effectively deployed. In other cases, a safe "landing zone" may not be present beyond the carotid stenosis because the device is best deployed in a straight carotid segment in the extracranial carotid circulation. Deployment of the device may cause vasospasm, and it remains imperative that device migration be prevented during the CAS procedure to prevent this complication. It is strongly advised that the device be placed in the extracranial segment of the carotid artery.
Finally, in a spirited debate over CAS versus CEA, Yadav10 and Comerota11 have passionately argued both sides of the debate over CAS versus CEA. Deaton12 and Criado13 in the same issue of Endovascular Today offer somewhat conflicting views from the standpoint of vascular surgeons as to which therapy will ultimately prevail.
The curiosity of brain hibernation and the ability of the brain to tolerate microembolization without clinical manifestations of stroke remain an enigma in clinical medicine. It is clear that endovascular physicians from various disciplines are capable of performing CAS with embolic protection. Excellence as an interventionist goes beyond the technical procedure and must incorporate clinical management and longitudinal follow-up to prevent additional cardiovascular events. This role is shared between the cardiovascular specialist and the primary care physician, and one should assume that the busy primary care physician, with few exceptions, has neither the time nor the expertise to continue to educate these individuals.
James A.M. Smith, DO, is board certified by the American Board of Vascular Medicine-Intervention. He is President of Kansas Endovascular Medicine Associates, and he recently founded River City Heart and Vascular Institute in Wichita, Kansas. Dr. Smith may be reached at (316) 462-1070.