Bridging the Gaps Surrounding Coronary Artery Stenting: The Current State of Carotid Stenting

I’m going to give you a perspective on where we see the current state of carotid artery stenting from the regulatory and reimbursement perspectives, and perhaps a bit of technical unmet needs and future prospects. Obviously, this is going to be largely a U.S.-centered perspective, so I apologize for those colleagues who practice in other countries around the world that may not be able to relate to some of these issues.

Regulatory Reimbursement

The carotid trials in the U.S. so far have shown that CAS (carotid artery stenting) is not inferior to CEA (carotid endarterecomy) in the treatment of high-risk patients — but only high-risk patients. Procedure-related stroke rates for protected intervention are 0–2% (for ipsilateral major stroke), and 3 to 7% for all stroke and other neuro events overall. MI events, both Q-wave and non-Q-wave, significantly lower than with CEA, and of course, a zero incidence of cranial nerve injury obviously. Importantly, in-stent restenosis rates, at least at two years, are as low as if not lower than those that follow CEA — a key finding to report for sure.
High risk for surgery has been defined: (1) Anatomic (the big one!), the one we care about the most in vascular surgery, (2) Medical. Medical co-morbidities precluding surgery do exist, but not often. It has been estimated that about 20% of CEA operations are being performed on so-called high-risk patients.
The regulatory and reimbursement status is as follows: The FDA, as you know, approved carotid stenting for both symptomatic and asymptomatic patients that are high risk for surgery. Two systems were approved fully, Guidant and Abbott Vascular. While Cordis received the first conditional approval, it has not yet been released because of reasons unrelated to carotid issues or their CAS system.
Almost without precedent, CMS approved payment (on 3.17/05) in a manner that is more restricted than the FDA approval. Reimbursement to the physician and to the hospital was approved only for patients at high risk for surgery with 70%+ lesions, but only for symptomatic patients, excluding asymptomatic patients. And reimbursement for procedures done under Category B IDE trials was preserved intact. So that’s where we are today in the U.S. So while for many years we have come to depend on the FDA to be the limiting factor and the bad guys increasingly, and perhaps more appropriately the folks when payment of the money in the paycheck are the ones who should be occupying that decision from this point on.
There are obviously many challenges in this area, and for all involved. But for vascular surgeons and other surgeons in particular, this implies nothing short of a revolution, and a re-invention perhaps…from conventional cut-and-sew surgery to image-guided therapy. Not an easy thing to do. Needless to say, the credentialing and training issues are enorrmous.
A consensus document was published about a year ago in a major journal that we at Union Memorial have decided to adopt almost literally (for credentialing) as it was published. It seems to make the most sense. The physician aspiring to be credentialed for carotid stenting for that hospital has to be endo-competent to begin with. In other words, don’t start your endovascular experience in the carotid artery. This is particularly appropriate for vascular surgeons. Thirty diagnostic angiograms, with one half as primary operators, 25 carotid stent procedures — again half as primary operator. And the hospital itself, the institution, must have a credentialing body and a mechanism to monitor, document and report outcomes. And the institution must meet certain requirements before it can be listed as an “approved” CAS hospital on the CMS website. There are already several hundred hospitals today in the U.S. listed in their website as credentialed to do carotid stenting.
What about technique? Is further evolution possible? Obviously the answer is yes. I would anticipate further, albeit perhaps minor, technical advances will continue to develop in the year to come. But echoing what you heard from Gary Roubin and his group this morning—and they were the pioneers of this — I think it’s really a very important perspective today that we are certain to follow. I feel that the most significant evolution is going to be this: identifying patients at low risk for CAS should become the purpose, not high risk for surgery. If not, you inevitably end up with the worst possible candidates and not very good numbers for morbidity and mortality. So interestingly for our own group and myself personally after having gained a great deal of confidence with this technique, and obviously the surgery since I am a vascular surgeon, I find myself today doing more CEAs than, say, two or three years ago because we are following or beginning to adhere to such principles.

Unmet Needs

Equipment: 10 designs that can address various types of lesions. We are only beginning to understand that today. Distal devices, protection devices that can be deployed and be effective in challenging anatomy. We have many difficulties and challenges at this time in that particular area. And as you heard, refinement in proximal occlusion devices that will undoubtedly have a role, at least in some patients. Data I believe are even more important. The consequences of microembolization — while some information is beginning to emerge, there are still more questions than answers. Age groups and other groups of patients who should not have CAS but CEA instead. What about asymptomatic patients? A huge area we all recognize. And no data essentially available today on long-term stroke prevention following carotid stenting.

Future Directions

Finally, a future perspective. Many of you have seen the graph as to the evolution (volume-wise) of CEA in the United States after the present day, where approximately 200,000 operations are being performed as a result of finally achieving or generating Level I evidence. It was predicted or forecast by financial firms in New York about three years ago that by the year 2004, CEA would nosedive and there would be a correspondent increase in carotid stenting. They were wrong because of the reasons that I mentioned before, and they did not anticipate the FDA and CMS decisions in that this would be a new day in terms of regulatory and reimbursement issues. However, one might wonder whether the prediction was wrong only in timing and that this is still going to happen perhaps 3–5 years down the road, especially once the issues relating to medications are sorted out. Will it happen? I think it will. I would personally not anticipate this being that steep. I think carotid endarterectomy is here to stay, it’s not going to go out the window. But its role may change in the future.
Another key piece to all of this in the puzzle is the fact that, almost unbelievably, that in the United States, about 75% of patients undergoing carotid artery surgery are asymptomatic. This is quite different in many other parts of the world but it certainly is a reality in the U.S. So nothing really is going change in the carotid landscape until decisions relating to medications are sorted out and these many important questions are finally answered.
In the end, I would say that carotid artery surgery is not dead or dying. Its demise was announced prematurely, but its role will change in the future. For instance, it would be inappropriate today to push the envelope and do CEA on certain patients such as voice professionals. So anatomty makes this a whole new ballgame. Interventional techniques and access implications will help determine which procedure will be used. The carotid plaque itself, the brain at the end of the wire, the multiple players involved will all be factors. And adding gas to a raging fire, the continuing controversy and disagreements have run in some of the trials, particularly SAPPHIRE as you well know. The data look strong for high-risk cases, but how many are there really, as I said before, and how many of these contemporary vascular surgeons treat these safely today? We are talking about 15+ years after NASCET. Caution.
And on the flip side, we must keep in mind situations where it would be inappropriate to push the envelope with carotid stenting. We can still do surgery. Surgery is a good operation and patients tend to do very well.
So, today, patients who are good candidates for CEA should continue to receive surgery – especially outside the confines of a well-controlled clinical trial.

These topics are discussed further by Dr. Criado in the following two editorials:

Editor's Corner: Carotid Angioplasty and Stenting: The “Perfect Vascular Storm” Revisited
by Frank J. Criado, MD, Editor-in-Chief
Vascular Disease Management
(also published by HMP Communications)

It was the December issue 2004 of VDM when we last editorialized about the status of carotid artery stenting (CAS) in these pages. And quite a bit has happened since! Taking into account the continuing strength and impact of carotid interventional developments, it seemed appropriate and timely to revisit the “CAS story” and provide a current update:

1. FDA Approval: Two CAS systems (stent/embolic protection filter) have received full approval and have been released for commercialization. Interestingly, they both came to rest within the domain of one single company (!) — the result of corporate transitions and acquisitions. The label indication is high-risk (for endarterectomy) only, both symptomatic (>50% stenoses) and asymptomatic (>80% lesions).
2. The reimbursement decision by CMS was a bit narrower than the FDA approval as asymptomatic patients were excluded altogether.
3. As predicted in the VDM 2004 editorial, carotid filters have now been “detached” from the CAS systems and — appropriately — reclassified as Class 2 devices (non-implants), thereby enabling regulatory approval through a 510k pathway. And so far, one such filter has been approved for carotid use within that framework: the Spider filter by ev3.
4. Technology-driven issues: (a) Aspects surrounding carotid stent design have recently received much attention, with some leading investigators questioning whether open-cell devices provide enough scaffolding and lesion exclusion. Preventing embolization, both immediate and delayed, and adequate lesion scaffolding and coverage are increasingly regarded as more important than flexibility and conformity. At a minimum, these evolutions will generate a demand for more related information, and a refocusing on closed-cell stent designs — and the carotid Wallstent. (b) Proximal occlusion and flow reversal systems continue to be unavailable in the United States, but we all agree that they will likely find an important place in our CAS armamentarium in the years to come. Testing of such systems in properly designed and carefully conducted clinical trials is eagerly awaited.
5. Enthusiasm for CAS continues largely unabated, but a number of important qualifications have emerged in the recent past:

(a) There is rapidly mounting evidence that carotid stenting is probably less safe than carotid endarterectomy (CEA) for octogenarians.
(b) There continues to be little if any evidence that CAS should be offered to non-high-risk patients — outside the context of a well-controlled trial. Several large clinical studies, both randomized and non-randomized, are presently commencing or in the planning stage. Such data will be several years in the making.
(c) The concept that anatomical suitability of the aortic arch and the common and internal carotid arteries is the most important determinant of success and potential CAS-related complications has been reaffirmed. And operator’s experience is also viewed as extremely important, but there are emerging data (from post-marketing surveillance studies) showing that the potential adverse impact of inexperience on outcome can be minimized through proper education and training — proctoring included.

So, what does the future hold for CEA? One thing for sure: surgical treatment of carotid artery stenosis is not going away any time soon! In fact, we find ourselves doing (proportionally) more CEA today than 2 years ago. CAS is clearly emerging as a worthy competitor to CEA, but one for which we still lack clearly defined indications. Personally, I would look at stenting as an option that will likely be used increasingly on patients who are at “low-risk for CAS” — as opposed to the “time-honored” strategy of offering the new therapy to patients at high-risk for CEA, often resulting in the selection of some of the most difficult patients for percutaneous intervention.
In the end, CAS developments continue to be pre-eminent in the vascular world. It has emerged — undeniably — as an important new treatment option for many patients. However, the boundless enthusiasm of the early days is (appropriately) beginning to be tempered by two powerful forces: data and reality! Stay tuned, and look for further VDM updates on this most important vascular topic within the next several months.

Vascular Disease Management - ISSN: 1553-8036 - Volume 3 - Issue 4 July/August - July 2006 - Pages: A2 - A2
Update published in Jan/Feb 2007 Vascular Disease Management (2007;4:A2–A4)

At the dawn of a new year, it should come as no surprise that yet a further update on the status of carotid stenting (CAS) is warranted. Developments of the past several months appear to have triggered (or quickened the pace of) changes in the carotid landscape, and I cannot say this is unexpected. In fact, the VDM Editor’s Corner in July/August 2006 saw it coming: “… the boundless enthusiasm (for CAS) of the early days is — appropriately — beginning to be tempered by two powerful forces: data and reality!” The truth is that new trial results and the reactions that followed seem to provide considerable ammunition to those who remain skeptical about the value of CAS. More to the point, the outcome of the EVA-3S1 and SPACE2 European clinical trials have caused — one might say — a “pendulum swing-back to carotid endarterectomies (CEA)” as they appear to show slight or clear-cut inferiority of CAS to surgical CEA. Flawed and imperfect as they may be, these studies cannot be simply ignored or tossed out as “irrelevant” or “biased”. And they are not alone in ‘questioning’ the safety and efficacy of CAS when compared to endarterectomy.
So, is this the end of the road for CAS? Has CEA won? I would say one cannot but conclude (with rare exceptions) CAS has failed to prove noninferiority to CEA when all currently available evidence is taken into account (Figure 1). In other words, CEA will remain — undoubtedly — the undisputed standard of care for treatment of most patients in the foreseeable future. But perhaps not forever…. Consider this:

• The “definitive” comparative large trials are only beginning or in the planning stages at present;
• CAS technologies, and embolic protection devices in particular, will continue to improve — perhaps dramatically;
• CEA, on the other hand, has reached a level of optimal performance from where it is unlikely to improve much further;
• Interventionists doing CAS continue to refine the technical conduct of the procedure and, more importantly, learn to select patients who should have surgery (or no intervention at all) instead.

For those of us who have gained large experience and confidence with CAS, there’s little doubt this is an elegant, effective and safe procedure — but only when applied wisely (Tables 1 and 2). Having said that, it is important to note that some of the current paradigms, especially those related to unfavorable anatomy, may change in the near future with the development of innovative access and anti-embolic techniques and devices.
In the end, it would seem that CAS is definitely here to stay, but its precise role in the management of patients with carotid artery stenosis remains largely undefined. It endures as a “hot political issue” for sure, going from “total triumph” in 2004 to “near-defeat” in 2006… Its future is probably assured but uncertain. However, I would caution vascular surgeons not to repeat the mistake of their interventional colleagues when they “announced” the demise of CEA prematurely.

References

1. Mas JL, Chatellier G, Beyssen B, et al., on behalf of the EVA-3S Investigators. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006;355:1660–1671.
2. SPACE Collaborative Group; Ringleb PA, Allenberg J, Bruckmann H, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: A randomised non-inferiority trial. Lancet 2006;368:1239–1247.