Carotid Artery Stenting: An Update

What are some of the implications of the SAPPHIRE* trial thus far?

I think that it has shown us that certainly in patients who have co-morbid conditions, that stenting protection is equivalent or superior to endarterectomy. It has a lower risk of complications, it has a lower restenosis rate, and certainly it has a lower risk of major ipsilateral stroke and myocardial infarction. I think one point that has been discussed is the definition of high-risk that we used. The definition of high-risk is really based upon the literature, upon a variety of conditions that have been described to increase the risk of surgery, such as previous surgery on the neck or cardiac conditions. We think that’s fairly well-validated. There’s also been some discussion about including myocardial infarction (MI) as an endpoint, which, again, we feel is scientifically appropriate. All of these patients have significant generalized atherosclerotic disease, and their major cause of death is MI. They frequently do have an MI during surgery or procedures. So it makes a lot of sense to include MI as an endpoint, and all modern trials, including CREST* study, and there were no differences in the neuropsychological testing between the angioplasty patients and the endarterectomy patients. Remember in CAVATAS, there was no emboli protection used. I think with these two major randomized trials, stenting with emboli protection is at least as neuroprotective as endarterectomy, and I suspect it is more neuroprotective.

What are some of the clinical studies going on at present?

 think there are several very important studies going on. CAVATAS 2 is very important, and CREST is important. There will be some large, low-risk, randomized and case-controlled studies starting in the U.S. in 2005, which will be very important also. We really are living in the golden age of carotid artery research and we will have a lot of data in the next few years.

How long do you feel it will be before there is a high number of physicians in the U.S. comfortable and experienced in performing CAS? 

I think by early 2006 or 2007, we will have a decent number of physicians. What you feel is the most important part of the CAS learning process for physicians? Many people have said that simply making the decision of whether or not to treat the patient is crucial. I agree, that is always the most important decision in any clinical scenario. Making the decision whether to treat or not, ie, clinical judgement, is definitely the most important thing. I think managing the patient, both before and after the procedure, is also very important. From a technical perspective, access remains the most challenging portion. We are working on simplifying that, and actually it's simpler than it used to be.

What’s the current status of the Angioguard device and Precise stent?

That particular device has not yet been commercially launched as yet. There is a post-surveillance registry going on with the Guidant device that's just starting up.

Your October 2004 New England Journal of Medicine article noted that “A larger sample might have provided more support for the secondary finding of the superiority of stenting.” Do you expect that finding in the high-risk symptomatic patients to be confirmed as future studies go forward?

I think there would be a high probability of that. If you look at SAPPHIRE, the treated patients, we actually did show superiority. In the intention to treat analysis, it was not inferior. And unfortunately, that study was designed basically as a non-inferiority study. I don’t think anybody realistically had expected stenting to do so well compared to surgery. I think everyone underestimated the true complication rate for surgery.

What about the procedure itself do you feel leads to its success?

I think people underestimate the stress to the patient of having surgery. They underestimate the impact of carotid occlusion for 15 minutes and they’re assuming that ischemia has no impact, and that only embolization has impact. I think that hypothesis is perhaps not correct. If you look at some brain biomarker studies, they clearly demonstrate a increase of release of these markers during carotid occlusion in surgery. I think it’s interesting research that probably needs to be pursued more, but it probably will not get pursued more, since endarterectomy will be performed less and less. With stenting, we really solved the Achilles’ heel, which was embolization. Once you take out embolization, which emboli protection devices are fairly effective at doing, the rest of the procedure is very elegant and very patient-friendly. The other factor is that the carotid artery, from a restenosis perspective, is actually the most forgiving artery in the body. It does not restenose. I think this may be because it is so large and perhaps the geometry. It’s the only place where you can perform endarterectomy. You can’t perform endarterectomy in the coronaries because the restenosis rates are too high — you have to do bypass. I think it is just a forgiving artery in terms of restenosis. The restenosis rates in SAPPHIRE were actually less for stenting than for surgery.

What is the plan for looking at asymptomatic patients?

One of our major areas of interest going forward is to look at vulnerable plaque and asymptomatic patients, and try and predict what asymptomatic patients are at risk of future stroke, as well as try to be more precise in which patients get treated. Right now, we don’t really have a very specific way of doing that. It is based only on the degree of stenosis. That probably is one of the poorer predictors of your risk of stroke, if the coronary arteries are any indication. In terms of the lower-risk studies coming up, they will include both asymptomatic and symptomatic patients. Most of the patients I am sure will be asymptomatic, given the distribution of what has been seen in previous carotid studies. These studies will be similar to SAPPHIRE except these patients will not have co-morbid conditions. Symptomatic patients will be at 50% stenosis, and asymptomatic patients will be at either 60% or 80% stenosis, depending on the study. There are multiple studies being planned.

Dr. Yadav can be contacted at yadavj@ccf.org

*SAPPHIRE: Stenting and Angioplasty with Protection in Patients at HIgh Risk for Endarterectomy *CAVATAS: Carotid and Vertebral Artery Transluminal Angioplasty Study