[ Scientific Activities - Actividades Científicas ]
Angioplasty and Stenting vs. Carotid Endarterectomy
for Carotid Artery Stenosis
CEA for Carotid Artery Stenosis
A/S for Carotid Artery Stenosis
A Protocol for A/S vs, CEA for Carotid Stenosis
Angioplasty and stenting (A/S) to treat cerebrovascular occlusive diseases are rapidly evolving techniques that are extensions of the extensive experience using similar methods for coronary and peripheral vascular diseases. The standard treatment for significant extracranial carotid artery stenosis (CAS) is carotid endarterectomy (CEA). The use of a percutaneous method of treatment is appealing, thereby avoiding surgery and a more costly hospitalization, while making possible treatment of sicker patients and less surgically accessible disease. However, only one controlled comparative study of these two methods has been completed (but remains unpublished), while a major trial is in the planning stages at this time. Therefore, comparison of these techniques must rely primarily upon a literature review if a rational protocol for their use is to be formulated.
CEA for Carotid Artery Stenosis
The value of CEA for symptomatic CAS was demonstrated by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST). In the NASCET (1), CEA was found to be so superior to best medical therapy (aspirin) that the trial was stopped before completion. For patients with stenosis >70%, the cumulative risk of ipsilateral stroke over two years was found to be 26% in the aspirin group and 9% in the post-surgical group. The rates for major stroke or death were 13. 1% and 2.5%, respectively. The peri-operative risk for stroke or death (the complication rate for only these two parameters) was 5.8%. For men with stenoses between 50 and 70%, surgery was still beneficial, even if there was a higher surgical risk due to cofactors such as coronary artery disease (2).
The ECST demonstrated a lower natural history of stroke while on aspirin, 16.8% over a three-year period vs. 26% over two years in the NASCET (3). The peri-operative stroke and death rate was 7%, with an additional 2.8% having a stroke over the 3-year postoperative period of observation, for a total morbidity/mortality from CEA of 9.8%. There was no benefit to CEA below the NASCET equivalent of 70% stenosis.
The value of CEA for asymptomatic CAS is controversial. The Asymptomatic Carotid Atherosclerosis Study (ACAS) evaluated patients with stenoses >60% over a 5-year period (4). The natural history of ipsilateral stroke of 11.0% (2.2%/year) was reduced with surgery to 5. 1% (1%/year). This reduction of only 1%/year was primarily in minor, not major, strokes. The ECST Collaborative Group followed 2295 patients with stenosis between 0 and 99% for an average of 4.5 years (5). The 3-year stroke risk for patients with the equivalent of >50% stenosis was 5.7%, one-half of the non-operated group in ACAS and only slightly more than the post-operative group in ACAS. In addition, the highest risk of stroke in asymptomatic patients occurs with stenosis >80% (6). Finally, the presence of symptoms appears to be more important than the degree of stenosis. A moderate stenosis (50-70%) in a symptomatic patient is of greater risk for ipsilateral stroke than a more severe stenosis in an asymptomatic one (1-6). After reviewing this disparate data, the Canadian Stroke Consortium has stated that there is insufficient evidence to justify surgery for any degree of asymptomatic stenosis (7).
Do the surgical morbidity and mortality statistics represent complication rates in the "real world"? The NASCET and ACAS were rigorously controlled, only the most skillful surgeons participated, and the patient populations were highly selected. For example, the ACAS patients did not have significant comorbidity factors such as cardiac, pulmonary, renal, or neurological disease. A recent review demonstrated an increased surgical morbidity and mortality in those asymptomatic patients who were not eligible for the ACAS due to comorbidity, compared to those who were ACAS-eligible (8). Another recent study has demonstrated an increased peri-operative death rate for non-selected Medicare patients undergoing CEA in the same institutions as those participating in NASCET (0.6% for NASCET, 1.4% for all Medicare patients), The peri-operative mortality rate for Medicare patients at non-study sites was 1.7% for a high-volume institution, 1,9% for average-volume, and 2.5% for low-volume institutions (9). In summary, the surgical morbidity and mortality statistics from NASCET, ECST, and ACAS are certainly applicable only to "best case scenarios'. Attempting comparison of any other type of treatment for CAS to surgery using these statistics may be very misleading.
A/S for Carotid Artery Stenosis
The potentially lower morbidity and mortality relative to surgery has propelled the development of this percutaneous, image-guided procedure. It is important to remember that the only parameters evaluated in the NASCET and ECST were ipsilateral stroke and death, but significant complications beyond these occurred. For example, in NASCET other complications were 7.6% cranial nerve palsies, 5.5% wound hematoma, 3.4% wound infection, 0.9% myocardial infarction, and 3.0% other cardiac complications, all related to the surgical procedure (1). These complications total 20.4% (assuming only one complication/patient). Added to the 5.8% rate of stroke and death, the total morbidity and mortality of CEA for CAS is 26.2%.
Other important considerations in favor of the less invasive A/S are the decreased length of hospitalization, thereby decreasing costs, and the ability to reconstruct arterial segments not easily accessible by surgery. Most importantly, A/S may be the procedure of choice for patients with other medical conditions making them significantly higher risks for CEA. Patients with any significant comorbidity were excluded from the major controlled surgical series, keeping the rates of morbidity and mortality falsely low.
Although no controlled studies of A/S have been published, there is a moderate amount of uncontrolled data. Mathur et al have performed A/S on 271 vessels in 231 patients with a mean age 69 years (10). Sixty percent of the patients were symptomatic, and 71% had significant coronary artery disease such that only 14% would have qualified for NASCET. There was a 6.9% peri-procedural stroke rate, but only 0.7% were major strokes (4 or more points increase on the National Institute of Health Stroke Scale and persistence for at least 30 days). In the subgroup that was NASCET-eligible, there was a rate of major stroke or death of 2.7%, significantly better than CEA for symptomatic stenosis. Theron et al, have reported on A/S in 136 patients using a distal balloon to prevent embolic fragments from reaching the brain. Only two patients had embolic complications in this series (11).
Unfortunately, other groups have experienced more significant problems. Dietrich et al performed A/S on 110 patients, 72% of whom were asymptomatic. Within the one-month peri-operative period, there was a 10.9% rate of stroke, death, requirement for CEA, or technical problems with the stent (12). A recent attempt was made to compare CEA and A/S for CAS in England, but the study was terminated prematurely after enrolling only 17 patients because of the high complication rate in the A/S group (disabling stroke in 3 of 7 patients)(13).
There is no doubt that there is a significant "leaming curve" to the performance of A/S, and that equipment (the stents themselves, along with guide-wires, angioplasty and guiding catheters) has improved dramatically within the last few years. The complication rate of major stroke and death at the University of Alabama at Birmingham was 7.2% in the mid-1990s, but dropped progressively over 5 years to 2.2% by 1998; there have been no major strokes or deaths within the last 12 months at that institutional). A complication rate of 2% or less is the desirable target, since the annual rate of stroke or death in the postoperative, previously symptomatic, NASCET population was 2.5%, while it was 2.2% in the asymptomatic population (ACAS). Obviously, one does not want to perform a procedure that has a higher complication rate than the natural history of the disease itself.
The only trial comparing CEA to A/S, the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) was conducted in Europe and is in preparation for publication. In this trial, 504 patients were randomized to treatment with either CEA or A/S. Only 26% (approximately one-half of the A/S group) of patients received stents. The vast majority (96.5%) was symptomatic, and the mean stenosis was approximately 70% by NASCET criteria. Major stroke or death occurred in 6.4% of the angioplasty group and 5.9% of the CEA group, an insignificant difference, but higher than desirable in both groups (15). A North American trial involving 2500 symptomatic patients with stenosis of 70% or greater will begin soon, the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), in which all patients in the A/S group will receive stents. This trial has been delayed while the principal investigators await the availability of the newest stent technology and decide upon the type of distal protection against emboli.
Another major issue is that of restenosis following stenting. There is no data to evaluate this rate in the carotid arteries, but it ranges from 20 to 40% over 6 months in other treated vessels (16). The restenosis rate following endarterectomy is unknown due to incomplete follow-up. A variety of techniques are being evaluated to decrease the restenosis rate with stents, including irradiation (17) and drugs (18). Finally, there are a number of different types of carotid occlusive disease, including the calcified, ulcerated, and acutely hemorrhagic. The indications and the relative risks of A/S for these subtypes are unknown.
A Protocol for A/S vs, CEA for Carotid Stenosis
It is far better to be prudent in the initial usage of a new, relatively untested procedure, no matter how good it appears to be on initial examination. At this time, until the CREST proves that CEA is equal to or better than CEA, A/S should be reserved for patients with symptomatic carotid artery stenosis who also have:
1. Significant cardiac, renal, or pulmonary disease.
2. A high or low carotid bifurcation, making surgical access more difficult.
3. A contralateral carotid occlusion, which increases the morbidity and mortality of CEA on the remaining carotid.
4. Recurrent carotid stenosis, which makes surgery more difficult.
5. Stenosis due to previous radiation therapy, which makes CEA more difficult.
6. Age of 75 years or older which increases the morbidity of surgery.
7. A relatively isolated hemisphere (poor collateral flow through communicating arteries), requiring the use of a temporary vascular shunt which increases the chance of surgical morbidity.
This protocol requires that the patient receive an extensive evaluation by experts in the diagnosis of neurological disease and treatment, and experts in the imaging evaluation of cerebrovascular disease. Such expertise will assure the following:
1. Proper patient selection based upon symptoms of cerebrovascular
disease and not upon other forms of neurological disease.
2. Accurate initial and precise post-procedural neurological evaluations to detect subtle neurological changes and complications.
3. Complete angiographic evaluation to define the vascular status and to exclude additional pathology, such as intracranial aneurysm and "tandem' stenoses.
4. The potential to perform A/S safely, given the degree of vascular tortuosity and other technical factors.
The practitioner undertaking A/S must be an expert in the performance of angiographic and neuro-interventional procedures, with the following experience:
1. Knowledge of all types of catheter and guide-wire systems so that the
procedure can be performed safely and expeditiously.
2. Knowledge of vascular angioplasty and stent equipment and techniques.
3. Knowledge of the potential intra-procedural and post-procedural extra- and intracranial angiographic hemodynamic complications, including those involving manipulation of the carotid bulb, and the potential for abnormal increased perfusion of the brain.
4. Knowledge of coagulation parameters and complications so that the proper anticoagulation and antiplatelet factors can be maintained or chemically manipulated, and thromboembolic complications prevented both during and after A/S.
5. Ability to perform intracerebral rescue. An intracerebral embolus is one of the most serious and potentially life-threatening complications of A/S. The practitioner must have the experience to perform intra-arterial intracranial thrombolysis.
If these fundamental guidelines are followed, A/S should prove to be a safe and efficacious procedure. Future studies will tell if A/S will, as expected, prove to be equally effective and even safer than CEA. Such efficacy and safety can only result if A/S is performed with the utmost skill by practitioners with the highest level of knowledge and experience.
. North American Symptomatic Carotid Endarterectomy Trial
Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with
high-grade carotid stenosis. NEngJMed 1991: 325: 445-453,
. Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. NEnglJMed 1998; 339: 1468-1471.
. European Carotid Surgery Trialists Collaborative Group. Randomized trial of endarterectomy for recently symptomatic carotid stenosis: Final results of the NMC European Carotid Surgery Trial (ECST). Lancet 1998; 351: 1379-1387,
. Asymptomatic Carotid Atherosclerosis Study Executive Committee. Endarterectomy for asymptomatic carotid artery stenosis. JAAIA 1995; 273: 1421-1428,
. European Carotid Surgery Trialists Collaborative Group. Risk of stoke in the distribution of an asymptomatic carotid artery. Lancet 1995; 345: 209-212.
. Chambers BR, Norris fW. Outcome in patients with asymptomatic neck bruits. N EnglJMed 1986; 315: 860-865.
. Perry JR, Szalai JP, Norris JW. Consensus against both endarterectomy and routine screening for asymptomatic carotid artery stenosis. Canadian Stroke Consortium. Arch Neurol 1996- 54: 25-28.
. Marcinczyk MJ, Nicholas GG, Reed JF, Nastasee SA. Asymptomatic carotid endarterectomy. Patient and surgeon selection. Stroke 1997- 28: 291-296,
. Wennberg DE, Lucas FL, Birkmeyer JD, et al. Variation in carotid endarterectomy mortality in the Medicare population: trial hospitals, volume, and patient characteristics. JAMA 1998; 279: 1278-1281.
. Mathur A, Roubin GS, lyer SS, et al. Predictors of stroke complicating carotid artery stenting. Circulation 1998; 97: 1239-1245.
. Theron JG, Payelle GG, Coskun 0, et al. Carotid Artery Stenosis: Treatment with Protected Balloon Angioplasty and Stent Placement. Radiology 1996; 201: 627-636.
. Dietrich EB, Ndiaye M, Reid DB, et al. Stenting in the carotid artery: Initial experience in 110 patients. JEndovasc Surg 1996; 3: 42-62.
. Naylor AR, Bolia A, Abbott RJ, et al. Randomized study of carotid angioplasty and stenting versus carotid endarterectomy: A stopped trial. J Vasc Surg 1998; 28-1 326-334.
. Personal communication, J. Vitek, NM, formerly University of Alabama-Birmingham.
. Personal communication, S. Chaturvedi, MD, Wayne State University School of Medicine, Detroit, MI.
. Rogers C, Edelman ER. Endovascular stent design dictates experimental restenosis and thrombosis. Circulation 1995; 91: 2995-3001.
. Fischell TA, Carter AJ, Laird JR, The beta-particle-emitting radioisotope stent (isostent): Animal studies and planned clinical trials, Am J Cardiol 1996; 78: 45-50.
. Tardif JC, Cote TF, Lesperance J, et al. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. NEnglJAIled 1997; 337: 365-372.