Katharine Krol, MD, is director of vascular and interventional radiology for CorVasc MD’s, a cardiovascular surgical group with clinics in Indianapolis and throughout Indiana. Krol is also the current president of the Society of Interventional Radiology (SIR), which she says has about 4,800 physician-members nationwide.
Krol estimates that to date, she has performed between 150 and 175 carotid artery stent (CAS) placements. She says the majority of these procedures have been done on patients in clinical trials, because for patients outside of trials, the Medicare or private insurance coverage is extremely limited.
For decades, the gold standard treatment for stenosis in the carotids has been carotid endarterectomy (CEA), a surgery in which incisions are made in the neck and plaque in the carotids is physically removed. Only in this century has CAS emerged as something of a competitor to CEA. All those interviewed for this article agree that despite CAS’s already somewhat turbulent history, it is a young procedure.
Compared to CEA, where stitches are visible on the neck after surgery, CAS is a noninvasive procedure. It requires a small incision, typically in the leg, so that a guide wire and the stent can be threaded along the aorta and into the carotid. Normally, a balloon device will precede the stent and open the artery blockage for the stent placement. It also is typical—and mandatory for Medicare reimbursement—that an embolic protection device, a tiny net or what Krol and her colleagues call an “umbrella,” is sent ahead of the stent and deployed to catch any emboli or plaque particles dislodged during stenting. The development and use of these umbrellas have been a key step in making CAS safe, say Krol and others.
|
| Katharine Krol, MD CorVasc MD’s |
Although CEA requires sedation and the attendant risks of surgical recovery, CAS is done with the patient mildly sedated but awake and would typically take no more than 30 minutes. The CAS patient is normally kept overnight at the hospital, but practitioners of CAS say in the future it will evolve into an outpatient procedure.
Krol calls the gold standard CEA “a surgery that works well.” It is low risk and typically has a good outcome as well as a short recovery time. “It would be hard to improve on that,” she says.
But one of the drawbacks of CEA, other than the invasiveness itself, is that scar tissue and other factors can lead to restenosis. In fact, Krol says, at least half of those patients on which she has performed CAS have been former CEA patients with restenosis in their carotids. Some have had multiple CEA surgeries on the same carotid before being designated for CAS to treat restenosis, she adds.
Krol says that the requirements for CEA reimbursement from Medicare are much looser than the standards for carotid artery stenting. Medicare covers only a limited number of symptomatic patients for CAS, but for CEA, Medicare covers asymptomatic patients with carotid stents.
“If you have an ultrasound that says you have 80% carotid stenosis, you will go right to surgery,” Krol says. “Also, with an MRA [magnetic resonance angiogram] showing stenosis, Medicare will pay for CEA.”
In fact, Krol says, the CEA reimbursement standards are so loose that sometimes, patients who do not even need it are undergoing the procedure.
“You can have an ultrasound or an MRA in a nonaccredited place showing stenosis that may or may not be there, and you will still be approved by Medicare for carotid surgery,” she says. “Ultimately, that is important, because people are getting surgery who don’t need surgery.”
She adds that CorVasc surgeons almost always perform catheter-based angiography on patients referred for CEA based on an MRA or ultrasound screening, and they do find cases where “the MRA or ultrasound was wrong.”
CAS Reimbursement
By contrast, Medicare reimbursements for CAS cover so few patients that most patients who receive the stents either have joined clinical trials, for which Medicare will pay, or pay privately.
As of now, Krol says, the only patients covered by Medicare outside of those in trials are symptomatic patients deemed to be at high risk for CEA who have exhibited carotid stenosis of 70% or more. Asymptomatic patients outside of clinical trials receive no Medicare coverage for CAS, Krol says.
Symptomatic patients for Medicare’s purposes, Krol says, are those who have had a previous stroke or have undergone a transient ischemic attack (TIA), a brief episode of vision loss or other manifestation of insufficient blood supply to the brain. In addition to being symptomatic, patients also must be at high risk for CEA, which means they must have anatomic or co-morbidity factors—heart trouble, for example—which makes surgery more risky for them than for typical patients, Krol says. What this boils down to is that very few prospective CAS patients meet the standards for Medicare reimbursement unless they enroll in trials.
Krol says that she frequently encounters patients with perhaps 95% carotid stenosis who are not symptomatic but who are at high risk for surgery. They are told by the surgeon that they absolutely need to have the artery opened, but that they are at high risk for surgery and are referred for carotid stent. Krol says that her only option is to enroll these patients in a clinical trial if they meet the requirements. Otherwise, the patients must pay privately or make arrangements for funding assistance.
“The families are all anxious and nervous,” Krol says. “They are being quoted $15,000 to $20,000 for the hospital part of it. The hospital makes me deliver the bad news.”
A different but somewhat analogous situation pertains for patients who have had a TIA or otherwise proved symptomatic but who want stenting rather than neck surgery and who are not in the surgically high-risk category. Like the high-risk-but-not-symptomatic patients, the symptomatic-but-not-high-risk patients can be covered by Medicare for CAS only if they are part of a recognized clinical trial. And joining a trial in which patients are randomly selected for either CAS or CEA could mean that some participants get CEA even though that is not their treatment of choice.
Explaining all this and helping patients navigate through their options, Krol says, “takes a lot of talking.”
Politics
Last year, Krol says, a group of doctors and physician’s organizations asked the Centers for Medicare and Medicaid Services (CMS) to reconsider and perhaps broaden the current coverage decision for carotid stenting. But any decision is not due until spring.
Krol says her hope is that Medicare will expand coverage to include all high-risk patients who would be covered by Medicare for CEA. It is very difficult to try to convince patients—who have been told that they must have a carotid intervention because they have a tight stenosis, but who are at high risk for surgery—that Medicare will pay for the high-risk surgery but not for the carotid stent, particularly after the surgeon has told them that surgery is too high risk and their only option is carotid stenting, Krol explains. Like many of her colleagues, Krol says the two procedures are roughly equivalent in forestalling stroke in symptomatic patients. In one prominent trial, she says, the follow-on stroke rate for symptomatic CEA patients was higher than for comparable CAS patients.
“When you talk to Medicare, they are very bright and caring, and they are trying to do the correct thing for patients, but their hands are tied in so many ways,” Krol says.
One of the big debates, probably the biggest debate, concerning carotid stenosis, Krol says, is what to do with asymptomatic patients. While symptomatic patients have a high rate of stroke risk, which Krol estimates at 30% to 40%, asymptomatic patients are much less at risk, having a stroke rate of 1% to 2% without intervention, she says.
So whether medical management of asymptomatic patients is the best course to pursue is a key question with which physicians and Medicare must wrestle.
“What I think the ultimate question needs to be is, do asymptomatic patients benefit from intervention of any kind?” Krol says. “If the answer is yes, then I think coverage should be equivalent for carotid stenting and surgery. Or if the answer is no, then surgery should not be covered either.”
Clinical trials are under way that will attempt to answer whether there is a benefit to asymptomatic patients from intervention; however, those trials have not been completed.
Barry Katzen, MD, is founder and medical director of the Baptist Cardiac and Vascular Institute with Baptist Healthcare, Miami. Like Krol, Katzen says, “The whole issue with carotid stenting is reduced risk of stroke.”
Katzen says his center has performed about 300 carotid stentings to date. He says that clinical trials already have shown a clear benefit to high-risk patients who undergo CAS or CEA and that CAS has shown itself to be “equal to or superior to surgery.”
Nonetheless, Katzen says it is doubtful that in its current reassessment Medicare will change its reimbursement requirements for CAS. Medicare, he says, “will continue putting the brakes on until there’s more data.”
But lack of data is only one reason for Medicare’s caution, Katzen says. Political factors also come into play. He says carotid stenting has been held to a higher standard than cardiac stenting ever was during its development.
“It’s a political hotbed because of the different doctors involved. It’s not just interventional radiologists [IRs]; it’s vascular surgeons, and vascular has been very vocal in commending surgery but not stenting,” Katzen says.
|
| Mark H. Wholey, MD University of Pittsburgh Medical Center |
Like Katzen, Mark H. Wholey, MD, is a CAS pioneer going back to the days, even before stents, when physicians were first trying balloon angioplasty in the carotids.
“Very few procedures in the history of medicine have had the resistance that carotid stenting has incurred,” says Wholey, who is chairman of the Vascular Institute at the University of Pittsburgh Medical Center (UPMC) and a clinical professor of radiology at the UPMC medical school. “These resistance factors have come from multiple sources, but especially through the reluctance of vascular surgeons to acknowledge carotid stenting versus endarterectomy, which is their largest single surgical procedure, or one of their largest.”
The FDA also was cautious, even the institutional review boards at prominent hospitals were “suspicious,” when CAS was first introduced in the mid-1990s, Wholey says. One reason may have been, as Krol explains, because early stents were like “coke cans” that could pinch down with neck movement, permanently reducing blood supply. But the latest generation of stents spring open after being pinched, just as natural arteries do, Krol adds.
Despite the technological advances, the resistance of vascular surgeons to CAS continues.
|
| Michael R. Jaff, DO Massachusetts General Hospital |
Michael R. Jaff, DO, is director of vascular medicine at the Massachusetts General Hospital (MGH), Boston, and an assistant professor at Harvard Medical School, Cambridge, Mass. Jaff does not perform carotid stenting himself, but he refers patients to CAS trials and follows them after treatment. In the bigger picture, Jaff also directs the MGH Vascular Ultrasound Core Laboratory, which has validated the ultrasound studies related to several large CAS clinical trials.
Jaff watched the comment sessions at the recent CMS reassessment of CAS coverage closely, and he says there was “a tremendous dichotomy” regarding expanded coverage, with neurologists and vascular surgeons opposed to expansion.
On the other hand, he says, interventional cardiologists joined IRs in supporting expanded coverage for CAS. It is the power of the cardiology lobby, in fact, which may have prompted CMS to reassess coverage in the first place.
Says Katzen, “Interventional cardiologists are more than on the [CAS] bandwagon—I’d say they’re driving the train.”
The key clinical trial for CAS now ongoing is the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). The trial is designed to compare CAS to CEA in those patients who have had a TIA or a mild stroke in the preceding 6 months (symptomatic) and in those patients who have not had any symptoms within the past 6 months but who have exhibited stenosis in screenings (asymptomatic).
Physicians who want to perform CAS are keeping a close eye on CREST, particularly because it includes a cohort of asymptomatic patients. But the results of CREST are still a couple of years away, according to Katzen. In the meantime, interventional cardiologists, along with IRs and peripheral vascular surgeons, are gearing up to perform CAS if and when it finally gets a green light for broader coverage. In fact, they already are leading the way in performing CAS. According to a survey reported by Wholey in 2000, of the several thousand CAS procedures then done, 62% were done by interventional cardiologists.1 By contrast, IRs did 21%, with surgeons performing the remainder.
The Clinical Picture
The preceding describes the reimbursement and turf status of CAS, but that is only part of the story. The other part is the clinical side, where CAS, according to the experts included herein, has not yet proven itself except for high-risk symptomatic patients.
In 2002, the early results of a major, randomized trial—Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE)—were reported on an interim basis by the stent manufacturer sponsoring the trial. Those results showed that of a total 307 high-risk patients, those receiving stents (156) at 30-day follow-up showed a major adverse effect (MAE) rate (defined as death, stroke, or myocardial infarction) of 5.8% compared with a 12.6% rate for the 151 who underwent CEA.
Carotid Stent Timeline |
|
1979: First successful carotid angioplasty performed in France Mid-1980s: First carotid stent devices developed 1987/88: First carotid stent implanted in Europe 1991: NASCET results published; provides first evidence of the utility of carotid endarterectomy (CEA) in preventing stroke 1992: CAVATAS initiated in Europe, North America, and Australia 2000: CREST begins to compare CAS with CEA December 18, 2000: HCFA generates a formal national coverage request for PTA of the carotid artery concurrent with stenting July 1, 2001: Medicare announced it would cover PTA of the carotid artery concurrent with stent placement when performed in accordance with FDA-approved protocols governing category B, IDE-approved clinical trials; physicians were required to report category III emerging technology codes 2001: CAVATAS results are published; CAS and CEA did not differ in 3-year event rate. CEA had higher complication rate, and CAS had higher restenosis rate. November 2002: Early results of SAPPHIRE presented at the American Heart Association meeting indicate MAE rate for CAS is roughly half that of CEA March 2004: Results of ARCHeR presented at SIR annual meeting; restenosis rates for CAS were lower than for CEA August 31, 2004: FDA approves Guidant Rx Acculink Carotid Stent System and Rx Accunet Embolic Protection System. September 1, 2004: CMS commits to covering patients with symptomatic 70% stenoses at high risk for surgery. For patients enrolled in FDA/IDE study, CMS covered symptomatic stenoses between 50% and 70%, and stenoses >80% that are asymptomatic in high-surgical-risk patients. November 2004: AMA CPT Editorial Panel releases two new 2005 category I codes for carotid stenting—one with distal protection (37215) and one without (37216). October 2006: NEJM published results of French trial halted after researchers found that the 30-day MAE rate for CAS was more than twice that for CEA. |
In 2004, Wholey presented at SIR the results of a series of trials called ARCHeR 1, 2, and 3 that he said also showed CAS to be safe and effective for carotid stenosis patients at high risk for surgery. In these trials, the restenosis rates following CAS were lower than the restenosis rates for CEA, Wholey told his SIR audience.
Wholey says now that these and other pre- and post-market trials, mostly underwritten by device makers, have established CAS as equal to or better than CEA for high-risk patients. But then came the CREST trial and some cautionary preliminary data, Wholey says.
When researchers separated those CAS patients 80 or older from the other CAS patients in the Carotid Acculink/Accunet Post-Approval Trial to Uncover Unanticipated or Rare Events (CAPTURE), Wholey says, the data showed that octogenarians who were asymptomatic had MAE rates from 7% to 10%, and for symptomatic octogenarians the MAE rate “could go as high as 16%.”
The upshot, Wholey adds, was that CREST pulled octogenarians out of the study because of the danger of stenting.
“Now we say, wait a minute—carotid artery stenting is great, but you can’t be over 80 and be symptomatic,” Wholey says. But this is unacceptable, he says, because octogenarians comprise 26% of the CREST registry. Their numbers are too great to exclude them from CAS if CAS is to become an established procedure and profitable.
“I don’t want to see carotid artery stenting for only a small subset of patients,” Wholey says. “I want carotid artery stenting to compete with carotid endarterectomy in all categories.” He says that aging patients can be successfully treated with CAS, and he would like to see a carefully constructed clinical trial to prove it.
One of the critical factors, he says, is simply patient selection in the aging group. Another critical factor is the experience of the physician performing the stenting. Wholey says doing octogenarians “takes a learning curve of at least 100 patients.” The villain is easily spotted, he adds. “The aortic arch is the Achilles heel.”
In threading a catheter through the aortic arch, tiny particles too small to be captured by embolic protection devices can break away and cause cognitive dysfunction or minor stroke in patients, Wholey says. He adds that older patients may not have the cerebral reserves to tolerate stenting, which becomes lengthy.
“If you have a complex aortic arch, and you’re not at the target lesion in 25 or 30 minutes, you shouldn’t do it. Walk away,” Wholey advises. “A technical failure without complication is acceptable; a technical failure with complication is not acceptable.”
He says that physicians also need more knowledge of stent design and what the impact of using exploratory techniques like blood flow reversal during stenting may have on patients. “We have a lot of unanswered questions.”
The French Study
Problems with aging patients are not the only cautionary tale associated with CAS.
In October, the New England Journal of Medicine published the results of a French study that compared CAS and CEA in symptomatic patients with severe carotid stenosis.2 That study was halted for safety reasons after researchers who had examined 527 patients found the 30-day incidence of stroke or death following CEA was 3.9%, but was 9.6% for CAS. The French study also claimed that 6-month stroke or death rates for the patients were 6.1% for CEA, compared with 11.7% following CAS.
Most of those included here, however, view the French study as flawed.
Katzen says the French study was completed using inexperienced doctors to do the stenting in some cases. Wholey agrees: “The French study was basically done by unqualified surgeons. I don’t even quote that study.”
Katzen adds, “The CREST trial has many more patients. I’m reserving judgment until the CREST trial is finished.”
Krol says the stroke rate for her CAS patients has not approached the French results. “I carefully monitor my patients,” she says. “My stroke range is 1% to 2% after 30 days.”
MGH’s Jaff says he agrees with the criticism of the French study, but he says carotid stenosis patients have learned of the French results and already are pulling out of the CREST and other randomized trials and opting for endarterectomy. “The way the press jumped on that study made a lot of patients nervous,” Jaff says.
He adds that the French study could be used by malpractice attorneys to litigate against physicians where CAS is followed by an MAE. But then, he says, competent defense attorneys could counter that the French study was flawed and that CAS was a proper treatment.
“The whole field of carotid therapy is a very dicey one” from the point of view of malpractice, he says, including CEA and medical management when there is a stroke. “In the case of asymptomatic carotid artery stents, you take somebody who is feeling totally well and the next day is paralyzed.”
A Bright Light?
Just when stenting the carotids was looking depressingly marginal from the standpoint of profitability, new research has raised hope that a whole new group of patients may benefit from the procedure, not just by eliminating stenosis but by restoring lost cognitive skills, to a degree that endarterectomy may not match. It could mean that otherwise asymptomatic patients who exhibit reduced cognition could begin by being screened for carotid stenosis and perhaps could benefit from CAS, even though they do not exhibit the classic carotid stenosis symptoms.
Krol suggests that preliminary findings are encouraging enough that restoring cognitive function “may be the place where carotid artery stenting has the strongest future. We have considered these patients to be asymptomatic, but maybe some are having memory problems or cognitive problems. If we can prove that, I think the benefit [of treatment with CAS] could far outweigh the risk.”
The physician responsible for this renewed optimism concerning cognitive restoration is Rodney Raabe, MD, an interventional radiologist at Inland Imaging, Seattle. Taking his cue from studies that seemed to suggest cognitive loss following coronary bypass surgery in the aorta, Raabe reasoned that blood flow to the brain might be the critical factor. In that case, CAS patients might show a cognitive improvement. He studied a group of 60 patients at his own clinic, including those who were asymptomatic with 80% or greater stenosis and those who were symptomatic with 70% or more.
“We did a fairly extensive battery of cognitive testing to see if there had been any change following stenting,” Raabe says. “We found that, overall as a population, there had been improvements.” In some cases, the improvements were startling, he adds. “I had patients going back to work; I had patients scheduled for nursing homes not going in them; there were dramatic lifestyle changes.”
Raabe says that CEA may have the same cognitive impact in some cases but not in others. “The CEA data shows improvement with high-grade stenosis, but other studies showed decline or no improvement.” He says that more testing needs to be done on restored cognitive function with both CAS and CEA. Raabe says CAS may have the edge in restoration because there is less restenosis. He also says that since it is less invasive, patients focusing on cognitive restoration may choose stenting.
Now, Raabe estimates, about 200,000 carotid artery procedures are done in the United States each year to eliminate stenosis. He estimates that, of those, at least 70% are CEA surgeries. But if his cognition studies prove out, he thinks the number of treatments will go way up.
“If this study is corroborated,” he says, “we’ll see double and triple the number of carotid arteries treated. If we see definite improvement with stenting and not so much with endarterectomy, the stenting numbers could go over a million. That would be a very good thing if you make protective devices.”
Wholey says that device manufacturers already have invested “an absolute fortune” in carotid stents and related technology without much recoupment.
Krol adds that she has talked to device company executives who say “their company livelihood depends on carotid stenting approval and it is taking off. But I don’t think we’re there yet,” she says.
Conclusion
Krol says that more research is needed to determine for which patients CAS works best and under what circumstances.
“At this point, the only trials completed have involved high-risk patients, and I think those are the only ones we can make any informed comment on today,” Krol says. “But I am confident enough that the procedure is safe that I’m willing to offer it to non–high-risk patients when they participate in authorized clinical trials.”
Wholey agrees that more research is needed on patients and technology too. But, he says, “There’s no question that carotid artery stenting is the coming thing. It’s a great procedure—the patient comes in for 20 minutes and they go home the next day with no restenosis, no stroke, no nerve damage. I would use it universally if I could get [the MAE rate] down to 5% for all symptomatics and 3% for asymptomatics. It would be universal, and there would be no need for surgery in any category.” But that day, Wholey admits, is not now.
Baptist Healthcare’s Katzen says that for those patients with severe stenosis who agree to participate in clinical trials, he is comfortable recommending stenting, but for patients not at high risk, he is happy to recommend surgery if they want it. “I think, in the end, carotid stenting will be comparable to but not superior to surgery,” Katzen adds. “Patients will have choices to make.”
At MGH, Jaff—who may be the most objective, because he performs neither stenting nor surgery—says his guess is that in 5 years, “all physicians who manage vascular disease will manage carotids. There still will be endarterectomy for some, and a reasonable subset will be eligible for carotid stenting. Everybody will benefit from better medical therapy.”
Jaff says indications of improved cognitive function with CAS are “very early, tantalizing information that would have a tremendous impact but will require large-scale studies to answer.”
Overall then, the case for CAS appears strong from some angles and questionable from others. Everyone awaits the outcome of CREST. Certainly, nobody interviewed here has given up on carotid stenting.
“I think carotid stenting is here to stay,” Krol says. “The question is just what its role is going to be. There’s a lot going on with it right now.”
George Wiley is a contributing writer for Axis Imaging News. For more information, contact .
References
- Wholey M. Carotid stenting: current status and prospects for randomized trials. Presented at: Annual Meeting of the American College of Cardiology; March 14, 2000; Anaheim, Calif.
- Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med. 2006;355(16):1660–1671.
