Parsing the Panel: Reactions to Expanding CAS to Standard-Risk Patients
Interventionalists reacted with expected optimism and satisfaction at the Circulatory System Devices Panel decision to extend the indication for carotid artery stenting (CAS) to patients even at standard surgical risk. The advisory panel to the US Food and Drug Administration (FDA) met January 26, 2011, and voted 7 to 3 in favor of the change.
Abbott Vascular (Abbott Park, IL) is marketing the device in question, the RX Acculink carotid stent system. In a press release, the company predicts the FDA will make its official decision within the year.
Currently, the product is approved only for patients who are at high risk for adverse events from carotid endarterectomy (CEA). Candidates must have a reference vessel diameter ranging from 4.0 to 9.0 mm at the target lesion and either neurological symptoms plus at least 50% stenosis or, in the absence of symptoms, at least 80% stenosis. For the expanded indication, average-risk patients must meet the same criteria with 1 exception: asymptomatic patients need only to have at least 70% stenosis.
In a telephone interview with TCTMD, Christopher J. White, MD, of the Ochsner Heart and Vascular Institute (New Orleans, LA), and president-elect of the Society for Cardiovascular Angiography and Interventions (SCAI) shared his excitement over the panel’s decision. “This is a huge event,” he said. “This may be the single most important thing that's happened in stroke prevention in a very, very long time.
“We've been doing carotid stenting since 1994 in this country,” Dr. White noted. “It's been a long slog. Some people have said that carotid stenting is the most studied interventional procedure in the history of medicine.”
CREST Makes the Case
William A. Gray, MD, of Columbia University Medical Center (New York, NY), told TCTMD he was unsurprised by the panel’s ‘yes’ vote, given that its decision was based on a fresh review of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), for which he served as an investigator.
“There was obviously dissension. It’s a controversial subject,” he said. Even so, the “panel’s decision really reflects the data that were presented to it, both by the FDA and by the sponsor. The data are so compelling that it’s hard to walk away from stenting as a reasonable alternative to surgery. If somebody’s still got problems with that, well, they’re not reading the data. . . . There isn’t a better trial you could do with clearer results.”
CREST randomized 2,502 patients with symptomatic or asymptomatic carotid stenosis to either CEA or CAS. Although there was no difference in overall adverse events between the 2 treatments at 4 years, MI was more common with CEA and stroke more frequent with CAS. Full results were published in the New England Journal of Medicine last July (Brott TG, et al. N Engl J Med. 2010;363:11-23), but the panel focused only on 2,307 patients who underwent their assigned treatments. In this per protocol analysis, CAS achieved noninferiority to CEA for the primary endpoint (death, any stroke, or MI ≤ 30 days plus ipsilateral stroke from 31-365 days) at a rate of 7.1% for CAS and 6.6% for CEA at 1 year.
Dr. Gray, who attended the advisory panel meeting, said the main points of debate did not center on clinical equipoise between stenting and endarterectomy but rather touched on other topics.
“The conversation would occasionally drift into issues around whether patients with asymptomatic carotid stenosis should have anything done at all, which is a reasonable question, but not the question in front of the panel,” he reported. Other concerns raised were whether the product label should include a warning that stents should only be implanted with use of embolic protection devices, and whether there should be restrictions on age. “It turns out that if you look more closely at how patients over the age of 80 did, outcomes were equal between surgery and stenting, though that’s not what has been in the literature,” Dr. Gray said, noting that although the sample size was small in this age group in CREST, the panel saw fit not to modify the indication.
Paradigm Shift for Clinical Practice
In short, said Dr. White, the FDA panel indicated “that carotid stenting is a reasonable alternative for revascularization in patients who are at risk for stroke, without any more elimination or criteria.” With few exceptions—such as those with very complicated or tortuous aortic arches, thrombus visualized in the lesion, or circumferential heavy calcification in the lesion—most patients with carotid artery disease would be considered candidates for either CEA or CAS, he noted.
Dr. White predicted that naysayers will continue to argue that the stroke risk seen with CAS outweighs the impact of MI observed with CEA, or question why stenting performed so much better in the North American-based CREST trial than in European trials.
Whither the Surgeons and Neurologists?
Yet none of the usual critics were present at the advisory panel’s public hearing, Dr. White pointed out. For instance, Tyrone J. Collins, MD, of the Ochsner Clinic Foundation (New Orleans, LA), spoke on behalf of SCAI. “Typically stakeholders besides industry will come and address the panel. It was surprising to me that neither the surgeons nor the neurologists took the opportunity,” he commented. “So I take that as their acceptance that CREST data are valid and do show clinical equipoise. . . . In the past they've been very vocal and vociferous, . . . so the fact that they weren't there this time maybe means that they've come to some level of acceptance. That would be nice.”
Another layer beyond FDA approval is reimbursement by the Centers for Medicare and Medicaid Services (CMS). Dr. White predicted that this process could take a while to resolve.
After the FDA makes its decision, “[t]he big change is ‘Now I have an on-label approved device to treat average-risk patients with carotid artery disease for stroke prevention.’ CMS is 1 payer. It just happens to be the gorilla payer, the big payer,” he said, explaining that the CMS decision is important because other payers likely will follow suit, but only “time will tell whether that [reimbursement] happens.”
Pending approval and CMS coverage, said Dr. Gray, a sizeable number of patients could become candidates for stenting. Over 100,000 patients undergo CEA each year in the United States, he reported.
US Food and Drug Administration. Meeting of the Circulatory System Devices Panel; January 26, 2011; Gaithersburg, MD.
- Dr. White reports having previously served as principal investigator of the CABANA study, which was sponsored by Boston Scientific.
- Dr. Gray reports having been an investigator in the CREST trial and serving as a paid consultant for Abbott.