The CREST trial: What have we learned and where do we go from here?

By Wesley S Moore

The CREST trial, performed in North America, is the largest trial to date which compares carotid endarterectomy with carotid artery stenting/angioplasty. Two thousand five hundred and two symptomatic and asymptomatic patients were randomised to one or the other procedure.

The first thing we learned was that the surgical and interventional management committees selected their participants well in that both endarterectomy and stenting had the lowest complication rates reported to date. The primary endpoint which included death, stroke, and myocardial infarction within 30 days, in aggregate, was 4.5% for endarterectomy and 5.2% for stenting. The difference was not statistically significant. This led the interventionists to claim equivalence of the two procedures.

The second thing we learned was that the simple addition of death, stroke, and myocardial infarction represents a design error. By doing this, in essence, we are saying that death=stroke=myocardial infarction which is clearly not the case. When we asked patients who did or did not have a complication, using a quality of life SF36 form, how each complication affected the physical and mental aspects of their life one year later, we found that major stroke was most profound, followed by minor stroke. One year later myocardial infarction, from the patient’s perspective, was a non-event. Therefore, when we look at the two most important endpoints, stroke and death, the rate for carotid endarterectomy was 2.3% versus 4.4% for carotid artery stenting (p=0.005).

Myocardial infarction is an important endpoint from the prognostic standpoint since the four-year mortality rate for patients having a myocardial infarction was 19.5% vs. 6.7% for patients without myocardial infarction. The surprise finding was that stroke, including minor stroke, had a detrimental affect upon survival. The four-year mortality rate for patients suffering a stroke was 20% versus 11.6% in patients stroke-free. Thus the four-year survival of endarterectomy and stenting patients was the same, but the stenting patients had an additional disadvantage of increased disability due to a higher stroke rate.

All primary events are important but not of equal consequence. What we should have done was to assign a point value to each complication. For example, death=10 points, major stroke=8 points, minor stroke=7 points, and myocardial infarction=5 points. Had we done that, the results are summarised in Table 1. Using this method of calculation, the aggregate adverse event points for stenting would be 535 compared with 391 for endarterectomy (p<0.0001).

Table 1

CAS=carotid artery stenting

CEA=carotid endarterectomy

The next important finding in CREST was that older patients did better with endarterectomy and younger patients did better with stenting. The inflection point occurred at age 70.

Finally, we found that women had a higher complication rate with carotid artery stenting. The aggregate periprocedural complication rate for stenting in women was 6.85% versus 3.8% with endarterectomy (p=0.047). Looking at the combined rates of death and stroke for women undergoing stenting, the number was even more dramatic, 5.5% versus 2.2% for endarterectomy (p=0.013).

It should now be apparent that the current technique employed for carotid artery stenting is not competitive with carotid endarterectomy. However, it is quite likely that the technical aspects of stenting are likely to improve and when it does, then stenting will become equal to and maybe superior to endarterectomy. The current technique employed for carotid artery stenting is a transfemoral approach with the use of distal embolic protection. It is quite possible that the less favorable results of stenting may be related to adverse anatomy of the aortic arch as well as vessel tortuosity leading away from the arch. In addition, distal embolic protection devices mandate traversing the lesion in the carotid bulb with a guidewire and device delivery system before the embolic protection device can be deployed. During these maneuvers, it is possible to dislodge thrombo-embolic particles leading to stroke. Newer approaches to stenting using a transcervical approach combined with flow reversal to prevent distal embolisation are currently under evaluation. We all eagerly await those results and hope that this modified less invasive procedure will be as safe as or perhaps safer than carotid endarterectomy.

Wesley S Moore is professor and chief emeritus, Division of Vascular Surgery, University of California Los Angeles, Los Angeles, USA.