Interview with Co-Principal Investigators of the ARMOUR Trial: Gary Ansel, MD and L. Nelson Hopkins, MD
What was the purpose and scope of the ARMOUR trial? What were the trial’s primary and secondary end points? ANSEL: The purpose of the trial was to test a proximal protection device for carotid artery stenting (CAS) called the Mo.Ma® Ultra Proximal Cerebral Protection Device (Invatec, Inc., Bethlehem, Pennsylvania). This is a flow-clamping device to allow for CAS. The primary endpoints were MACE, which included any myocardial infarction, stroke or death. What was the patient population studied? HOPKINS: We studied the patients at high surgical risk for carotid endarterectomy (CEA): 225 subjects were in the intention-to-treat registry and 37 were roll-in patients, for a total of 262 patients. What kind of inclusion criteria were used? HOPKINS: Patients considered to be at high risk for CEA surgery either based on either anatomical or physiological measures. For example, any patient who had a carotid artery stenosis that was out of reach for an endarterectomy procedure, or was in a surgically hostile neck — such as in patients with recurring restenosis who had significant scarring from previous surgery; patients who had major previous neck surgery or immobility of the neck; patients with occlusions in the other carotid artery who therefore do not have very good collateral circulation. There were also physiological parameters that guided patient selection: patients with multivessel coronary artery disease, unstable angina, heart failure, ejection fraction Overall, what do you think the results of this trial will mean for treatment of carotid artery disease in the U.S.? HOPKINS: I think the potential impact is huge. Needless to say, nobody is happy about the fact that the CMS (U.S. Centers for Medicare and Medicaid Services) came out on December 9th with a continued non-coverage decision for about 90% of patients with carotid stenosis who would be potential candidates for CAS. Patients who were symptomatic within the previous 2 weeks have been shown to be at increased risk for CAS, yet those patients are at greatest risk for stroke from the natural history of the disease. We would like to be able to treat these patients, but the risk of stenting appears to be greater in this subset. The exciting thing about the ARMOUR study is that it shows a 0% risk for recently symptomatic patients and a very low risk (2%) in another high-risk subset: patients >80 years of age. The results of this trial show that CAS is a potential solution for patients who were previously thought to be at high risk for CAS. Equally exciting is the technology involved, which allows us to treat patients with carotid artery stenosis in much the same way surgeons do, in that flow is completely stopped, the procedure is performed, and then any debris is removed by aspirating the debris-laden blood. This is very similar to what is done in surgery, which has been shown to be quite safe overall in selected patients. The Mo.Ma device allows the operator to produce the environment that is created in surgery. I think this is a potentially very exciting advance in the treatment of patients with carotid stenosis. ANSEL: I think the CMS’s decision not to cover CAS procedures may be evidence that the government is more financially-driven than patient-care driven. We physicians know that there are patients who are best treated by CEA and those who are better treated by stenting. The government seems to consider these as competing technologies and is just worried about the cost, whereas physicians are more focused on patient outcomes. The Mo.Ma device is another piece of equipment with success rates to offer patients who may be best treated with a stent versus endarterectomy. To see a 0% stroke rate in the symptomatic patients and a very low stroke rate in all patients across the board shows that the field is maturing, and hopefully we can mature as a country as well and arrive at providing what’s best for patient care, especially as the universal health-care debate carries on. How much is the Mo.Ma device used in Europe? Do you think usage will be similar in the U.S.? HOPKINS: I was just at a meeting in Europe where I asked a couple of practitioners about this. They told me that proximal protection devices are used in about 60% of the patients who undergo CAS. There are still vascular surgeons in Europe who only perform endarterectomies, but Professor Setacci in Italy, for example, has performed a very large series of carotid stenting cases, and I think he would very proudly say that his CAS results are as good as, or better than, surgery. Unfortunately, I think that the CMS has been persuaded by practitioners from some of the other specialties who don’t see stenting as a primary method of treating a disease. I think CMS is waiting for the CREST results to come out in February 2010 at the Stroke meeting. The CREST trial started in 2000, thus it spans 8 years and used technology which we would consider outmoded today. Proximal protection devices were not available for use in the CREST trial, and it began as a symptomatic-only trial. My fear is that the results of the symptomatic patients in CREST will be much like some of the European trials that have shown an increased stroke risk in these patients undergoing CAS. However, we now have a lot more experience treating carotid disease; we have a much better idea of who to treat and who not to treat with CAS, when to use proximal embolic protection, and so on. As so often happens with medical technology advances, randomized, prospective trials are almost obsolete before the results are ever published. I am hopeful that we will learn a lot from the CREST trial. It is important to emphasize that no one trial has all the answers. We must carefully analyze the data from CREST, learn what we can and incorporate that into our practice and move on. Meantime, we must try as much as possible to enter patients in ongoing trials so we will keep learning. CAS has been studied more thoroughly than any new procedure in memory. We are learning that both CEA and CAS have an important role in treating patients with carotid stenosis. Every new trial teaches us something and the disparity in trial results shows us that we cannot simply focus on one trial such as CREST and ignore the others. CAS will have a role and CREST will help us better understand what that role is. Based on what we now know, I suspect CREST will show slightly better results for CEA in symptomatic patients where a first-generation filter was used for embolic protection and noninferiority for CAS in asymptomatic patients. ANSEL: I agree, Nick. I don’t think the CMS goals are the same as the physicians’. The great thing about the Mo.Ma device is its simplicity. The average procedure time was 30 minutes, whereas with the Mo.Ma device, the average clamp time was What is the learning curve with the Mo.Ma device compared to other embolic protection devices? ANSEL: The ARMOUR trial involved 20 U.S. sites that were allowed to enroll up to 3 patients as learning cases. The entire 20 U.S. sites only enrolled 37 learning cases, thus only a little more than 1 case per site was required for learning. And to achieve these kinds of results with such a short learning curve is phenomenal. What is it about the Mo.Ma device’s design and deployment that make it so easy to use? ANSEL: The Mo.Ma is comprised of a single catheter that has a balloon on one end and a balloon down the shaft where there is an opening. After images are taken with the regular catheter, you just put a wire up in the external carotid artery (ECA) and advance the Mo.Ma device over that wire, leaving the tip of the Mo.Ma in the ECA where one balloon is inflated to block blood flow through to the main carotid artery; then another balloon is inflated in the common carotid artery, thus providing balloon clamping of the carotid system, like surgeons do. There is an opening between those two balloons through which wires and stents can be advanced. The nice thing about this device is that many of these patients have a lot of tortuosity or highly angulated blood vessels after the blockage, which is what makes it difficult to use distal protection devices, which require that the blockage be crossed without protection and then the operator must attempt to find a straight vessel to place it. With the Mo.Ma proximal protection device, no landing zone is required; you can just barely put the wire through the blockage, advance the balloon and stent, aspirate the blood with any debris, and then remove the catheter — and the procedure is finished. This simplicity explains why the procedure times are so short. The results are so good with this device because the surgical procedure is so closely mimicked. Proximal protection devices provide the operator with another tool to tackle cases that were heretofore difficult to treat. The Mo.Ma device represents very complementary technology in the operator’s armamentarium: there are filter devices for certain situations and proximal protection devices for others. We are getting to a point where, no matter what the patient’s anatomy, there is a high likelihood that an appropriate tool will be available to treat that patient safely. That is the key: better technology, more technology that allows more patients to be safely treated. The Mo.Ma device gives us another arrow in the quiver for treating complex carotid stenosis. How does the Mo.Ma differ from the GORE Flow Reversal proximal protection device? ANSEL: Both proximal protection devices work along the same physiology of either clamping the flow in the internal carotid artery (blood flow to the brain is not clamped), or reversing the flow actively during the procedure, as with the GORE Flow Reversal System (W.L. Gore & Associates, Flagstaff, Arizona). Both devices provide proximal protection during intervention of the carotid blockage. The GORE device has also shown excellent results with a very short learning curve. This device is a little more complex because the operator must gain access to the vein and ensure that the different flows are traveling in the right direction during the procedure. Instead of saying one device is better than the other, however, I would say that these are very complementary devices that accomplish the same goal with a slightly different approach to the same physiology of limiting the ability of emboli to travel to the brain during the procedure. Can the Mo.Ma device be used in patients with the string sign or thrombus at the treatment site? HOPKINS: Yes, absolutely. The Mo.Ma can be used in such patients. One thing we fear is thrombus sitting in the lumen of a carotid artery and relatively high flow going forward. You don’t want to put something through that area where the thrombus sits, as it may be knocked loose. This device avoids that risky scenario and offers an effective endovascular approach to safely treat patients with the string sign or a clot in the artery. The risks are quite high — over 15% — with lumen thrombus in CEA procedures. Thus, that group of patients for whom there was no solution, now have a potential solution. Is it reasonable in a Medicare-approved patient to consider this the “procedure of choice” and use the filter as a “fall-back” system? HOPKINS: Certainly, that would be the operator’s choice. Obviously, you want to do what is best for the patient. If, for example, the patient is completely intolerant to flow arrest, then it would be best to place a filter for backup. As we have said, these various devices fit into an armamentarium of tools we can use, rendering these procedures much safer. The individual patient’s anatomy and situation will dictate the type of device used. The Mo.Ma device is a wonderful addition to that armamentarium and will solve some problems that we were not able to solve before. Is there potential for embolization when the external carotid occlusion is performed if the carotid stenosis involves the bifurcation of the common carotid artery? ANSEL: We depend on being able to cross the external carotid artery, and severe stenosis of the external carotid artery would usually be considered a contraindication to using a device that would be placed there. Certainly, if there is a blockage located lower than the ECA, you would have to think twice about using this technology, which demonstrates the utility of complementary devices. In that particular patient, it may be more beneficial to use a distal embolic protection device so that the bifurcation lesion involving the external carotid artery can be treated. HOPKINS: I agree. It’s a great example of the utility of complementary technology. Do you foresee an expansion of Mo.Ma device use beyond its current indications? HOPKINS: I would think so, given what has happened in Europe, where the Mo.Ma has become a very popular device in many situations. We have already discussed one of the indications that is beyond the current instructions for use, and that is for treatment of intraluminal thrombus, or string signs. It has become increasingly clear that this is a potentially excellent use for this device. Another situation in which I think the Mo.Ma device will prove to be very valuable is in acute stroke. In acute stroke patients, you do not want to open the carotid artery and allow all that clot that to advance into the brain. This device will allow you to occlude the carotid artery, remove the clot, stent the artery, remove all the loose clot, and then reestablish flow. The Mo.Ma device is therefore a potentially great addition to our stroke protocols. ANSEL: The other thing we need to remember is that research protocols are meant to test a device or drug in a particular patient population; they have to meet certain criteria so it can be compared to the traditional therapy. It’s up to physicians to determine exactly how to use the device based on its physiology or pharmacology to expand that indication. If we limit the usage of drugs or devices to just the tested populations, we would leave the vast majority of patients untreated. That is where the practice of medicine comes into play. Do you think proximal protection is better and safer than distal protection in carotid artery stenting procedures? HOPKINS: As we said earlier, these are complementary technologies, so I would not advocate using one over the other in a general way. Rather, I would encourage everyone to remember that we must take into consideration the individual patient’s symptoms, physiology and anatomy, and then consider the devices available and decide what is best for that patient. Fortunately, an increasing number of devices are now available and operator experience is growing such that CAS will eventually replace endarterectomy for most carotid stenoses. We are now unquestionably at a point where we know enough about this technology to choose the right device for the right patient for the right situation and achieve very good results, as we saw in the ARMOUR trial. Again, these are complementary technologies, and we should not think of them so much as competitive ones. I have been performing endarterectomies for nearly 30 years, and it is crystal clear that there are a significant number of patients (about 20%) who are at increased risk for CEA, notwithstanding a few “macho” surgeons who say there is no such thing as high risk. CAS and CEA are remarkably complementary in that when one procedure is clearly higher risk, the other is usually a better choice. ANSEL: I agree with all of those points. It’s when we try to say that one thing is better than another that we lose sight of what is best for patients. Physicians are very skilled at identifying what type of technology is best for their patients in certain populations. As Nick said, these are all complementary technologies, just as stenting and surgery are complementary to each other. It is ultimately the physician’s job to identify which patient populations will benefit from a particular therapy.
_________________________________________________ Co-Principal Investigators: Gary Ansel, MD, Midwest Cardiology Research Foundation, Columbus, Ohio, and L. Nelson Hopkins, MD, University at Buffalo Neurosurgery, Buffalo, New York. E-mail: email@example.com Disclosures: Dr. Ansel discloses that he has been a member of the speakers’ bureau for and received research grant support from Abbott, Guidant Vascular, Boston Scientific, Cordis J&J, Invatec and W. L. Gore & Associates.
VASCULAR DISEASE MANAGEMENT 2010;7:E37–E40