EXACT/CAPTURE-2: Postmarketing Carotid Stent Registry Data

Susan Jeffrey

April 03, 2007

April 3, 2007 (New Orleans) — New data from FDA-mandated postmarketing surveillance studies show low rates of death, stroke, and myocardial infarction (MI) on follow-up and some evidence of better outcomes with increasing operator experience.


Results from the Emboshield and Xact Post Approval Carotid Stent Trial (EXACT) as well as preliminary data from the second Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events (CAPTURE 2) were presented here at the i2 Summit 2007, a program run in tandem with the American College of Cardiology (ACC) 2007 Scientific Sessions and cosponsored by the ACC and the Society for Cardiovascular Angiography and Interventions (SCAI).

"Both of these postmarket approval studies continue to compare favorably with landmark pivotal trials," William A. Gray, MD, from Columbia University Medical Center, in New York, concluded in his presentation.

Postmarketing Data

Several carotid stent systems have been approved by the FDA, but on the condition that postmarketing surveillance studies be undertaken both to monitor for unforeseen adverse events and track the dissemination of these technologies out of the clinical trials and into the hands of less experienced operators.

At the recent meeting of the Society of Interventional Radiology, for example, postmarketing data from the CASES-PMS study were reported, focusing on results using the Cordis PRECISE Nitinol Stent and the Angioguard XP Embolic Capture Guidewire System in patients with high-grade stenosis and either a high risk for carotid endarterectomy (CEA) or failed endarterectomy. Researchers reported that major adverse events (MAE) at 30 days, a composite of death, MI, and stroke, occurred in 5% of patients, and at 1 year, cumulative MAE occurred in 11.9%.

The EXACT study presented here looked at postmarketing data on 1500 patients enrolled from multiple sites who received carotid stenting using the Emboshield distal-protection system and the Xact self-expanding stent, both by Guidant/Abbott Laboratories. All patients where treatment with the stent and/or protection device was attempted were included, with outcomes determined by an independent clinical-events adjudication committee. Of 1500 patients, 148 (9.9%) were symptomatic, the remainder asymptomatic.

In his presentation, Dr. Gray reported the EXACT data relative to those from the pivotal SECURITY trial that had formed the basis for approval of this system. "It's important to make the disclaimer that although I'll be showing you different studies side by side, they were not meant to be compared as prespecified analyses, so . . . please take them with a grain of salt and understand no statistical comparison is undertaken as a result," he said.

There were some differences in the demographics between the 2 trials, notably that the SECURITY cohort was somewhat older, with more symptomatic patients; this latter finding is probably related to the fact that stenting high-risk symptomatic patients is now reimbursed by the Center for Medicare & Medicaid Services, and therefore patients need not be enrolled in a registry to receive treatment on-label, he noted.

"The bottom line is that it appears that for death, stroke, and MI, as well as for any stroke subset, the EXACT data set shows better outcomes than the SECURITY data set," Dr. Gray told a press conference here. The reductions seen were driven principally by all strokes, rates of which were lower in EXACT than in SECURITY, he noted.

EXACT vs SECURITY: 30-Day Outcomes in All Patients

End Point
EXACT*
(%)
SECURITY
(%)
Death, stroke, and MI
4.6
7.5
All stroke and death
4.5
7.2
Major stroke and death
1.8
3.0
Death
1.0
1.0
All stroke
3.9
6.9
Major stroke
1.3
2.6
Minor stroke
2.7
4.3
MI
0.2
0.7
*The data for EXACT include only the most serious event for each patient and only the first occurrence of each event.

Not unexpectedly, symptomatic patients had almost double the rate of events seen in the overall group, with a stroke and death rate of 8.6%, but in asymptomatic patients, the rate was a "very pleasing" 4.0%, he said.

One of the reasons for postmarketing surveillance was to assess transfer of this technology into the community, so outcomes were analyzed on the basis of physician experience. Operators were stratified into 3 levels: level 1 operators had had experience with both carotid stenting and this specific system and required no further training; level 2 operators had carotid stenting experience but not with this system, and so had an intermediate level of training; level 3 operators were new to both carotid stenting and this system and had a day-and-a-half training session, he said.

Level 1 operators handled the highest volume of patients, almost 14 patient per physician, level 2 operators handled 6 patients per physician, and level 3 operators had the lowest number, 3.4 patients per operator.

Outcomes by operator showed a trend to better outcomes for the more experienced physicians. The stroke and death rate for level 1 operators was 3.2%, 4.6% for level 2 operators, and 8.8% for level 3 physicians, although Dr. Gray pointed out that this last rate was based on only 34 patients, "so it's tough to make much out of it, but there's a higher complication rate."

For octogenarians, a patient group that has been shown to do less well than younger patients, all stroke and death in EXACT was 1.7% for level 1 operators and 1.1% for level 2 operators; level 3 operators did not have enough of these patients for analysis, he noted.

CAPTURE 2 vs EXACT

Dr. Gray then reported data from another contemporary registry data set, CAPTURE 2, using another stent system, Guidant's RX ACCULINK carotid stent system and the RX ACCUNET embolic protection system in the first 597 patients, 66 of which were symptomatic, 531 asymptomatic. CAPTURE 2 began enrollment in March 2006 at 195 sites and is ongoing.

Demographics were similar in age and symptom status between the groups, and there were no significant differences in outcomes between these 2 data registries.

EXACT and CAPTURE 2: Outcomes for Symptomatic vs Asymptomatic Patients
End Point
EXACT (%)
CAPTURE 2 (%)
All stroke/death


All patients
4.5
5.2
Symptomatic
8.6
9.1
Asymptomatic
4.0
4.7
Major stroke/death


All patients
1.8
1.3
Symptomatic
2.9
1.5
Asymptomatic
1.7
1.3

There was no difference in outcomes between the registries for patients older than and younger than 80 years of age, contrary to findings of higher rates of stroke and death in the pivotal clinical trials, Dr. Gray said.

Finally, they compared findings in CAPTURE 1, the first-generation postmarket surveillance study, with those in CAPTURE 2 and EXACT and showed a "pleasing trend" to reductions in death and stroke across the studies, in both symptomatic and asymptomatic patients. "So it appears that for postmarket surveillance registries, the trend is positive and is improving for the stroke patients," Dr. Gray said.

CAPTURE 1, CAPTURE 2 and EXACT: All Stroke and Death
Patients
CAPTURE 1 (%)
CAPTURE 2 (%)
EXACT (%)
All patients
5.7
5.2
4.5
Symptomatic
10.6
9.1
8.6
Asymptomatic
4.9
4.7
4.0

Moderator for the press conference here was William Knopf, MD, from the Atlanta Cardiology Group, in Georgia. He called the EXACT findings "provocative in a number of ways, not the least of which is showing that the learning curve for the first time seems to be very important, whereas in prior trials, it didn't."

Dr. Gray responded that "the effect of experience on carotid stenting outcomes seems likely, and there were trends in that direction in larger trials like the CAPTURE trial, although they didn't reach statistical significance." However, although in this trial there did appear to be something of a trend in the level 1 and 2 operators toward better outcomes, the least experienced operators did not treat enough patients to make any informative statement.

Open- vs Closed-Cell Stents?

Finally, during this presentation, Dr. Gray pointed out that there were no apparent differences between EXACT and CAPTURE 2, "at least on this first observational look, between a closed-cell system, Xact, and an open-cell system, ACCULINK, in excess of 2000 patients analyzed."

During the press conference, Dr. Knopf also asked about this finding. Previously reported data from Europe had suggested that closed-cell systems are associated with fewer complications than open-cell systems. Dr. Gray pointed out that, unlike those previous data, EXACT and CAPTURE 2 provide results that are prospectively gathered and adjudicated independent of the operators, and in this setting there doesn't seem to be any difference.

"I would say that the European data are quite flawed inasmuch as there was a lot of selection bias potentially, the adjudication was not as rigorous as it was in this trial where there was an independent adjudication committee," and a number of closed-cell stents were not represented, he noted.

Dr. Knopf speculated that the difference may lie in results with the octogenarian patients, where closed-cells stents might be more able to trap atherosclerotic material and prevent its being embolized distally.

"I think that what we're going to see is whether there is any effect of stents — and I remain unconvinced that there is an effect — it may be blunted by the fact that there's a filter distally," Dr. Gray responded.

Proposed CMS Changes Controversial

In February, the CMS announced a proposal to expand coverage for carotid artery stenting (CAS) procedures to include those done in symptomatic patients with 50% stenosis or higher or asymptomatic patients with 80% stenosis or more who are considered at high risk for CEA.

To date, procedures are covered if they are done in symptomatic patients with stenoses of 70% or higher at high risk for CEA, using FDA-approved stenting systems and embolic-protection devices at facilities with CMS approval to perform these procedures. Many neurologists have expressed concern, though, about the expanded coverage to asymptomatic patients, where many feel there is not yet sufficient evidence of benefit. The CMS is currently receiving comments from interested groups on the proposed changes.

"In general, the CMS is considering expanded coverage for patients at high risk for surgery, and we applaud that," Dr. Gray told Medscape. However, there is concern among interventionalists over the proposal that reimbursement require a vascular surgeon to state that a given patient is high risk, he said. "This is unprecedented in medicine, and not in the best interest of the patient."

"There has been a lot of commentary from the various societies, and clearly we're not on the same page," Dr. Gray said. "The problem then is that the CMS is not getting a unified message."

Dr. Gray disclosed that he has received consulting fees/honoraria from Abbott Vascular, Interventional; Access Closure, Interventional; Mercator Interventional; and Ortaco Inc, Interventional; among others.

American College of Cardiology 2007 Scientific Sessions: Abstract 2409-5. March 24–27, 2007.

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