Monument Valley in Arizona

Opinions: Asymptomatic Carotid Stenosis: A Neurosurgeon’s Perspective


Joseph M. Zabramski, MD

Division of Neurological Surgery, Barrow Neurological Institute, Mercy Healthcare Arizona, Phoenix, Arizona

Key Words : opinions

The results of the recently published Asymptomatic Carotid Atherosclerosis Study (ACAS) trial clearly demonstrate that surgery plus best medical management significantly reduces the risk of stroke when compared to best medical management alone in patients with asymptomatic carotid artery stenosis.1 The findings of this trial represent the best scientific evidence to date regarding the treatment of this group of patients.

The ACAS study was subjected to the highest peer-review standards from its conception through its completion. This prospective, randomized trial involved 39 clinical centers in the United States and Canada. A total of 1,662 patients were randomly assigned to one of two treatment groups: carotid endarterectomy plus best medical management (n = 825) or best medical management alone (n = 835). Patient follow up was excellent. Complete follow up was available in 98.9% of the surgical group and in 98.7% of the medical group. The study was designed to demonstrate a 35% difference in 5-year event rates between the two groups with 90% power based on a two-tailed test of the null hypothesis with a p value of 0.05. The primary end point was 30-day perioperative stroke or death plus subsequent stroke ipsilateral to the treated carotid artery. After a median follow up of only 2.7 years, sufficient data had accumulated to demonstrate a highly significant difference (p = 0.004) between the estimated 5-year ipsilateral stroke rates of 11% for the medical group and 5.1% for the surgical group and the study was discontinued. This outcome amounts to a relative risk reduction of 53% in favor of surgical treatment. In addition, the benefit of carotid endarterectomy appears to be long lasting: the Kaplan-Meier survival curves for the ACAS trial maintained divergent slopes throughout the period of follow-up.1

The study also demonstrated that in the hands of qualified surgeons carotid endarterectomy can be performed with extremely low risks. The overall risk of perioperative stroke and death was 2.3% in the surgical arm of the trial: This included five patients whose strokes were a direct result of angiographic evaluation as well as two patients who experienced strokes and one patient who diedbefore surgery. In the 724 patients who actually underwent carotid endarterectomy, there were 10 nonfatal strokes and 1 fatal myocardial infarction for a perioperative risk of only 1.5%.

Recognition of the importance of angiographic complications to the perioperative risks in the ACAS study has spurred the use of alternative methods of evaluation. In 1996 the majority of patients with asymptomatic carotid stenosis are evaluated preoperatively with noninvasive procedures (duplex carotid ultrasound and MR angiography).3 At our institution, fewer than 10% of patients undergo conventional angiography before carotid endarterectomy for asymptomatic stenosis. The use of noninvasive testing further improves the risk-benefit ratio for carotid endarterectomy. Eliminating angiographic complications from the ACAS study data increases the relative risk reduction in favor of surgery from 53% to 61%.

When all subgroups are considered, the results of the ACAS study clearly favor surgery over best medical management alone; however, several important subgroups comprised too few patients to allow statistical comparisons, thus creating potential difficulty in clinical interpretation of the study findings. For example, for the end point of perioperative stroke or death plus major ipsilateral stroke the relative risk reduction in favor of surgery was 43%, but this difference was not significant (p = 0.12). The lack of statistical significance does not mean that carotid endarterectomy does not prevent major stroke, only that the study was not designed to address prevention of subgroups of stroke.

Another example of subgroup analysis without sufficient power involves the different outcomes for men and women in the ACAS study. For the primary end point of perioperative stroke and death plus ipsilateral stroke, the relative risk reduction favoring surgery was 66% for men but only 17% for women. These results are often used to argue that carotid endarterectomy may not be efficacious in women. Almost all of this difference, however, was due to the fact that the perioperative complication rate for women (3.6%) was more than double that in men (1.5%). If angiographic and surgical complications are excluded from the analysis, the risk reduction in favor of surgery for women in the ACAS study increases over three-fold, from 17% to 56%. The relatively small number of women in this study makes any hard interpretation of this data impossible. Of the 1,662 patients recruited only 565 were women, with approximately equal representation in the medical (n = 284) and surgical (n = 281) arms. Our own experience and a review of the literature fail to support the conclusion that there is a significant difference in the surgical risks between well-matched groups of men and women undergoing carotid endarterectomy.

Much of the debate in the literature regarding the results of the ACAS study has had to do with whether surgical treatment is cost effective. The figures used for length of stay and reimbursements in such discussions are often outdated. In 1996, the typical carotid endarterectomy patient is admitted on the morning of surgery and discharged 24 to 48 hours later. Based on the average allowable Medicare reimbursements for fiscal year 1995, the cost for carotid endarterectomy at an urban teaching hospital is approximately $12,500, which includes all professional fees and hospital charges for the diagnosis-related group (DRG) 05.7 This figure represents an average of values used for Medicare reimbursement in the Northeast, Midwest and West Coast regions. Applying these figures to the total cost for the 725 carotid endarterectomies performed in the ACAS study yields $9 million dollars. These costs must be compared to the savings accrued by preventing 50 strokes in this same group. All patients experiencing stroke are assumed to incur costs in the acute period consisting of inpatient hospitalization and professional fees. Costs for acute care have been previously estimated at $7,000 per patient.8 In the literature 40% of patients surviving stroke will require inpatient rehabilitative services, at an estimated cost of $22,000 per patient.5,6,9 Using the figures, the total cost for acute and rehabilitative care for 50 patients with stroke is $0.73 million. The cost of chronic care is considerably greater but often overlooked. Based on the results of the Framingham study,215% of stroke patients require long-term nursing home care at an estimated cost of $3,100 dollars/month per patient,10 for an estimated $1.4 million over 5 years. Economic costs of stroke arising from lost productivity are difficult to assess; however, assuming that one-third of stroke patients are of working age (average income of $40,000/year) and that two-thirds of those surviving would be unable to return to work, this would amount to an estimated $2.0 million in lost wages. Adding these figures together yields a total savings for the prevention of 50 strokes of nearly $4.1 million. This figure does not include an estimate of the costs of the reduced quality of life suffered by both patient and family. Based on the above figures, the difference between the cost of carotid endarterectomy and savings from stroke prevention in this group is $4.9 million, or approximately $1,300 per patient per year over the 5 years of the study. This figure compares favorably with the difference in pharmaceutical costs of treating this same group of patients with Ticlid® versus aspirin.

In the American Ticlopidine Aspirin Stroke Study (TASS), a total of 3,061 patients with a history of transient ischemic attacks were randomized to receive ticlopidine or aspirin.4 At a median follow up of 3 years, there was a modest (compared to the ACAS study) but statistically significant (p = 0.024) risk reduction of 21% in favor of ticlopidine (10% versus 13% cumulative risk of stroke for ticlopidine and aspirin, respectively). The average cost to the patient for a 1-month supply of ticlopidine is $90 dollars ($1,100 dollars per year) compared to $4 dollars for generic formulations of regular aspirin and $12 dollars for enteric-coated aspirin.

Although discussions of cost-effectiveness are interesting, they are rather cold-blooded. Irrespective of cost, few of our undertakings as physicians are more worthy of our efforts than the prevention of stroke and the attendant disabilities that rob our patients of dignity and independence. In this regard, the results of the ACAS study are clear. When carotid endarterectomy is performed by qualified surgeons in properly selected patients, it significantly reduces the risk of stroke.


  1. Executive Committee for ACAS Study: Endarterectomy for asymptomatic carotid artery stenosis. JAMA 273:1421-1428, 1995
  2. Gresham GE, Phillips TF, Wolf PA, et al: Epidemiologic profile of long-term stroke disability: The Framingham study. Arch Phys Med Rehabil 60:487-491, 1987
  3. Heiserman JE, Zabramski JM, Drayer BP, et al: Clinical significance of the flow gap in carotid magnetic resonance angiography. J Neurosurg 85:384-387, 1996
  4. Helgason CM, Tortorice KL, Winkler SR, et al: Aspirin response and failure in cerebral infarction. Stroke 24:345-350, 1993
  5. McGinnis GE, Osberg JS, DeJong G, et al: Predicting charges for inpatient medical rehabilitation using severity, DRG, age and function. Am J Public Health 77:826-829, 1987
  6. McGinnis GE, Osberg JS, Seward ML, et al: Total charges for inpatient medical rehabilitation. Health Care Financ Rev 9:31-40, 1988
  7. Nussbaum ES, Heros RC, Erickson DL: Cost-effectiveness of carotid endarterectomy. Neurosurgery 38:237-244, 1996
  8. Oster G, Huse DM, Lacey MJ, et al: Cost-effectiveness of ticlopidine in preventing stroke in high-risk patients. Stroke 25:1149-1156, 1994
  9. Schartenberger JZ, Ill KC: Financing of health care for elderly stroke patients (State of the Art Reviews). Phys Med Rehabil 3:653-658, 1989
  10. Wiener JM, Illston LH, Hanley RJ: Sharing the burden: Strategies for public and private long-term care insurance. Washington: Brookings Institute, 1993