Understanding the CREST results. Carotid stenting vs surgery: Parsing the risk of stroke and MI
ABSTRACTThe Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is the largest randomized prospective study to date to compare carotid artery stenting and carotid endarterectomy in a patient population similar to that seen in everyday practice. CREST showed stenting and surgery to be equivalent in terms of the composite end point of stroke, myocardial infarction (MI), or death within 30 days, as well as for the rate of stroke at up to 4 years (N Engl J Med 2010; 363:11–23). Importantly, the risk of major stroke was low with either intervention. However, the results need to be considered in the context of the impact of each procedure on stroke and MI.
KEY POINTS
- In CREST, stenting and surgery had similar combined rates of stroke, MI, and death when performed by highly qualified interventionalists and surgeons in carefully selected patients.
- The risk of periprocedural stroke was higher with stenting; most of those strokes were nonmajor. Both major and nonmajor strokes were associated with decreased quality of life in long-term follow-up.
- Endarterectomy was associated with higher rates of periprocedural MI than stenting.
- Endarterectomy carried a significantly higher rate of cranial nerve damage than stenting.
WHAT DO THE CREST FINDINGS MEAN?
CREST is the largest trial to date to compare stenting and surgery. It is an important addition to the literature, not only because of its size, but also because it focused on a real-world patient population. For this reason, its results are more applicable to patients seen in primary care clinics, ie, with peripheral vascular disease, coronary artery disease, diabetes mellitus, hypertension, and smoking.
As noted, previous studies of endarterectomy had strict inclusion and exclusion criteria, which selected against patients at high surgical risk. Therefore, the CREST findings are of greater relevance when comparing stenting and endarterectomy.
Periprocedural and long-term neurologic outcomes
CREST showed similar findings for the composite end point of periprocedural stroke, death, or MI (ie, within 30 days of the procedure) and long-term stroke, establishing similar outcomes in patients undergoing stenting and surgery.
However, an analysis of the individual components of the composite end point showed significant differences between the two treatments. The risk of ipsilateral periprocedural stroke was higher with stenting; these events were defined as nonmajor by NIHSS criteria. The risk of contralateral stroke was similar and low with each treatment.
While the increased risk of periprocedural ipsilateral stroke was not synonymous with an increased risk of major stroke, post hoc analysis showed that any stroke was associated with decreased physical and mental health at 1 year. Therefore, patients who had even a minor stroke did worse from a physical and mental standpoint, a finding that argues for the superiority of surgery in selected patients at risk of periprocedural stroke.
If periprocedural stroke is excluded, the risk of long-term ipsilateral stroke was similar for each treatment, and extremely low (2% for stenting, 2.4% for surgery). Despite this, given the importance of periprocedural minor and major stroke, better predictive models are needed to identify patients at risk of procedural neurologic events. These prediction models will allow better patient selection.
The CREST data and medical therapy
The rates of stroke in this trial were similar to those observed with current medical treatment (approximately 1% per year), especially for patients with asymptomatic disease. Such findings introduce fresh controversy in the necessity of performing either procedure for this patient subset and may lead to further studies evaluating current medical therapy vs intervention.
Periprocedural myocardial infarction
Vascular surgery has long been associated with high cardiovascular risk, especially an increased risk of periprocedural MI.30 Findings from CREST provide further evidence of the risk of MI with endarterectomy in a real-world patient population. Given the evidence of a strong correlation between periprocedural cardiac enzyme elevations and adverse outcomes, the increased incidence of periprocedural MI is worrisome.31 As with risk assessment for periprocedural stroke, better predictive models are needed for patients at risk of cardiovascular events during endarterectomy.
Procedural complications
Carotid endarterectomy entails incisions in the neck with disruption of tissue planes, as opposed to catheter entry site wounds with stenting. The more invasive nature of endarterectomy thus carries a higher risk of wound complications. In fact, in the NASCET trial, the risk of wound complications was 9.3%.10,19 In CREST, surgery carried a higher risk of wound complications compared with stenting (42 vs 0 cases), although stenting involved more periprocedural transfusions, presumably due to retroperitoneal bleeding in four patients.
Use of general anesthesia is also associated with adverse outcomes.17,18 In CREST, 90% of endarterectomy procedures required general anesthesia, whereas none of the stenting procedures required this.
Cranial nerve palsy is an often overlooked but real complication after these procedures. Cranial nerve palsies can lead to vocal, swallowing, and sensory problems that can have a transient or permanent impact on quality of life. In CREST, as in EVA-3S, SAPPHIRE, and ICSS, this risk was substantially higher with surgery,23,25,27 although the long-term consequences of these palsies were not found to affect quality of life at 1 year of follow-up.
