SAN ANTONIO — The largest-ever, head-to-head comparison of stenting versus surgery for treating severe carotid artery stenosis showed a marked effect of age, with patients older than 70 having fewer adverse outcomes after carotid endarterectomy and patients younger than 70 having fewer complications following carotid angioplasty and stenting.
Although the highly anticipated results from the decade-long Carotid Revascularization Endarterectomy vs. Surgery Trial (CREST) seemed, in simplest terms, to show a dead heat between carotid stenting and surgery (see table), the results reported at the International Stroke Conference actually revealed statistically significant and clinically important differences between the two treatments.
The statistically significant interaction between patient age and outcome will likely play a major role when physicians and patients now decide which intervention to favor for a specific patient.
The CREST results also showed another significant difference between carotid surgery and stenting: Surgery led to a 1.2% increased absolute rate in the incidence of periprocedural MIs, whereas stenting produced a 1.8% increase absolute rate of periprocedural strokes, a finding that will force patients and their physicians to ask themselves which complication they would rather risk.
The patients in CREST answered that question, at least in part, via another outcome measure. Assessment of patient physical and mental quality of life with the 36-item Short Form (SF-36) Health Survey a year after treatment showed that patients who developed new strokes, even “minor” strokes, had statistically significant reductions in both their mental and physical well-being compared with baseline, whereas patients who developed new MIs had, on average, no significant changes in their SF-36 mental and physical scores, Dr. Wayne M. Clark reported while presenting the CREST results.
The CREST report prompted some experts to highlight that the stenting results in the trial came from selected, experienced operators and that it would be a leap to expect comparable results from physicians who were not trained as well as the more experienced operators.
CREST randomized 2,502 patients with either symptomatic carotid stenosis or asymptomatic severe carotid stenosis (at least 60% blockage) at 108 sites in the United States and 9 in Canada. The patients' average age was 69 years, a third were women, and 47% were asymptomatic. The analysis showed no significant effect from either gender or symptom status on outcomes.
The age effect produced the sharpest distinction between stenting and surgery, and confirmed evidence that began emerging a few years ago that carotid stenting poses a special problem for elderly patients. In fact, some of the first suggestions of safety problems that can occur when stenting elderly patients came from the lead-in phase of CREST, a stage that involved nearly 1,600 patients who underwent carotid stenting in the early 2000s as operators in the study established their stenting expertise. The problem has been attributed to the increased difficulty and danger of placing stents and embolic protection devices through elderly patients' tortuous and atherosclerotic arteries.
“I think it's likely that putting in the embolic protection device sets off strokes. Until we have more data to show whether or not the age effect is real, I will take it into account in my patients,” commented Dr. J. Donald Easton, a neurologist at the University of California, San Francisco. Dr. Clark reported the age effect as a continuous variable, without specifying any point estimates of the effect. But based on the line graph he showed, patients who underwent stenting at age 65 had a roughly 20% reduced risk for an adverse perioperative or long-term outcome compared with those who underwent surgery, whereas at age 60 the relative benefit from stenting was about 35%, and at age 50, the rate of adverse outcomes after stenting was less than half the rate after endarterectomy.
The primary adverse-event measure used in CREST was the composite rate of any stroke, myocardial infarction, or death during the 30 days following treatment plus the rate of any ipsilateral stroke during long-term follow-up of up to 4 years. This rate was 7.2% for stenting and 6.8% for endarterectomy, with similar rates of ipsilateral strokes occurring from 31 days to 4 years (2.0% vs. 2.4%, respectively).
In contrast to younger patients, at age 75, the rate of adverse outcomes after stenting rose by about 35% compared with surgery; at age 80, the adverse-outcome rate was more than 50% higher with stenting than with surgery; and at age 85, the adverse event rate was roughly doubled by stenting in comparison with endarterectomy. In patients who were 70 years old, the adverse event rates were essentially identical regardless of which procedure was used.