The Advance of Carotid Stenting

How frequently are you performing carotid stenting cases? At the Cleveland Clinic, we typically do five to ten per week. What are your criteria for patient selection? Currently we are treating patients who are at increased surgical risk for carotid endarterectomy. Increased risk includes severe heart disease, previous carotid surgery, restenosis and advanced age. How do the risks of carotid stenting differ from a carotid endarterectomy? The SAPPHIRE study showed stenting had roughly half the complication rate of carotid surgery in patients that were at increased risk for carotid surgery. Overall, when we looked at the combined endpoint of death, MI and stroke, we found an almost 50% reduction with carotid stenting. How is the equipment utilized during a carotid procedure different from coronary intervention equipment? There are a lot of similarities and some differences. We do use guide catheters like we use in the coronaries, but the guides are shaped differently than coronary guides. For example, there’s a sheath called "H1," made by Cordis. It works pretty well in most cases. We don’t just put the guide in the carotid we advance over a wire or a diagnostic catheter. Unlike in the coronaries where we’re just engaging the ostium, in a carotid case, we put the guide fairly far up the common carotid artery. You don’t want to traumatize the artery, so we do it very carefully. Then we use emboli protection devices, typically filters, that we use to wire the artery and the lesion. We expand the filter after we get across the lesion, and usually predilate the lesion with a coronary balloon, normally a 4 x 20 or 30-mm balloon. Then we place a nitinol self-expanding stent, such as the Cordis Precise stent, which has a sheath delivery system. We advance the delivery system through the lesion, then pull the sheath back, allowing the stent to open up. Since the stent is not on a balloon, we come back with a balloon and post-dilate the stent. At the very end, we collapse the filter and take it out. What type of drug therapy is involved with a carotid procedure? Same as with the coronaries: aspirin, Plavix, premedications, and we use heparin during the procedure, keeping the ACT at 250-300. We do not use GP IIb/IIIas, because we have the emboli protection devices available. We don’t use bivalirudin routinely, because we don’t have a lot of data, but it’s certainly possible that bivalirudin would be used for the carotids also. In your opinion, how should physicians be trained and credentialed to perform this procedure? Very good question. I think there are multiple pathways for physician training and credentialing. You want to start from a background of experience in the coronaries, so you should be an experienced coronary interventionalist. In addition, if you’ve done some peripheral intervention, particularly renal intervention, it would be helpful. If the physician has used self-expanding stents, that’s also helpful. I would then recommend entering a training program that’s industry-sponsored. You would undergo some didactic training on cerebrovascular disease and angiographic anatomy, as well as simulator experience (we’re finding simulators are quite helpful in getting hands-on experience). This would be followed by a visit to a training site to observe cases and finally, proctoring for the first 3-4 cases. We have a steady stream of people coming to the Cleveland Clinic who spend one or two days with us to get some training. Can you talk about your involvement with Angioguard and describe the device? Angioguard was the first filter to prevent embolization. It is very simple to use, is very atraumatic to the vessel and can be used in a variety of anatomy including severe tortuosity. We were always concerned with embolization during carotid angioplasty and stenting. We initially thought that just by refining the technique we could make it diminish, but found that was not the case. I thought that we needed some type of filter device. I initially discussed this with a few companies back in the mid-to-late 1990s, when there was not a lot of interest in this problem or technology. As a result, I started a company in Minneapolis, called Angioguard, to make a filter. It was then acquired by Cordis. The FDA panel reviewing Angioguard was concerned about treatment of asymptomatic patients. What are your thoughts on that issue? I think they were really confusing a variety of different issues in their deliberations. Asymptomatic patients are routinely operated on in the U.S. and Europe. In fact, the majority of patients roughly 70% of those who get an endarterectomy are asymptomatic. Mainly, the issue was whether asymptomatic patients should be treated at all, but that’s really not an FDA panel issue. That’s a medical practice issue, and there is good evidence that asymptomatic patients should be treated. The ACST study (Asymptomatic Carotid Surgery Trial) from Europe, recently published in the Lancet¹, demonstrated a 50% reduction in stroke risk in asymptomatic patients with a 60% stenosis. I think the evidence is pretty clear that if you do the procedure safely, asymptomatic patients do benefit. In SAPPHIRE, we were pretty conservative, only treating asymptomatic patients with 80% stenoses, where stroke rate is even higher. So I think that the FDA deliberations got off-track a little bit. We know from SAPPHIRE that even though those patients were high-risk, their median life expectancy was greater than 5 years. Even if they had co-morbid conditions, treating asymptomatic disease is beneficial for these type of patients and will reduce future risk of stroke. One important point the FDA did make is that if the patient is very sick, very high risk and also asymptomatic, then consideration should be given to not treating the patient at all. You do have to use good judgment. If you have a patient with a lot of other problems, treating an asymptomatic lesion may not be necessary. Do you recommend distal protection be used with every carotid procedure? Yes, I think we have pretty strong evidence now there are multiple studies, both in the U.S. and Europe, demonstrating a substantial lowering of the stroke rate if you use emboli protection devices. These studies were not randomized, however; they were sequential studies, with the same operators. In France, there was a recent study called the EVA3 study. It was a randomized study comparing carotid endarterectomy to carotid stenting. In the carotid stenting arm, the operator had the option of using or not using emboli protection. They stopped that practice prematurely because they found that in the first 50 or so patients, the stroke risk was dramatically lower in those treated with an emboli protection device. Right now, I think that’s about the closest we can get to a randomized study. The evidence is pretty strong, so I don’t envision further studies which will allow you do to carotid stenting without emboli protection. The FDA approval of carotid stenting mandates the use of an emboli protection device. Diabetics seemed to fare very well with carotid stenting in SAPPHIRE. Yes. We’re going to be publishing the data and I also presented data at the May PCR meeting. Diabetics really have a very dramatic result and even greater benefit with stenting compared to carotid surgery. I think it’s the same as with the coronaries, where we see higher event rates with the diabetics. In general, I think a less-invasive therapy lowers that risk when compared with carotid surgery. Why do you think restenosis rates appear to be so low in the carotids? I think there are several factors. One, the artery is larger. That’s the biggest factor. Also, the stent is different it’s a nitinol self-expanding stent, versus a stainless steel balloon-expandable stent. The vascular territory and bed are different also. Are there still questions that you feel are important to try and answer? There are a couple of big questions that we still need to figure out. The first is in regard to patients who are not at high risk with carotid surgery. How should they be treated? Will they do better with carotid stenting? The CREST trial is ongoing, but that’s only for symptomatic patients. We will be doing a large trial to try and answer these questions, a study looking at non high-risk patients who are asymptomatic, as well as symptomatic low-risk patients. Another big question is regarding patients with moderate stenoses. Which 60% asymptomatic patient needs to be treated? That’s an important question. I think the current approach of treating every 60% asymptomatic patient is perhaps a little too broad. What can we expect to be happening in the near future with reported data and potential devices? I think we’ll see further subset analyses from SAPPHIRE and other studies. We’ll be getting a better handle on restenotic patients and diabetic patients, as well as ultrasound information and the angiographic information. Redefining the criteria for restenosis after stenting on the basis of ultrasound is an important area. The current criteria are a poor predictor of restenosis after stenting; we frequently find that repeat angiography does not demonstrate restenosis even though velocities may be moderately elevated on ultrasound due to the presence of the stent.

1. Halliday A, Mansfield A, Marro J, et al. "Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: Randomised controlled trial." <i>Lancet</i> 2004 May 8;363(9420):1491–1502.