Which patients benefit from carotid stenting? What recent trials show

The Endarterectomy Versus Stenting in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) study

This recent multicenter, randomized study¹³ was designed to determine if stenting is as good as (not inferior to) carotid endarterectomy in patients with symptomatic carotid stenosis of at least 60%. The primary end point was to be the incidence of stroke or death within 30 days after treatment. However, the trial was stopped early after the inclusion of 527 patients for reasons of safety and futility.

Results. The 30-day incidence of any stroke or death was higher in the stenting group (9.6% vs 3.9%). The relative risk of any stroke or death after stenting as compared with endarterectomy was 2.5. The 30-day incidence of disabling stroke or death was also higher in the stenting group (3.4% vs 1.5%; relative risk 2.2). At 6 months, the incidence of any stroke or death was 6.1% after endarterectomy and 11.7% after stenting (P = .02). There was a trend toward more major local complications after stenting and systemic complications after endarterectomy. Cranial-nerve injury was more common after endarterectomy than after stenting (as expected). Overall, death and stroke rates were lower at 1 month and 6 months with endarterectomy than with stenting.

The Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE) trial

This randomized, multicenter study,¹⁴ published in 2006, was also designed to compare the safety and efficacy of carotid stenting and endarterectomy. Some 1,200 patients with symptomatic carotid artery stenosis confirmed by ultrasonography were randomly assigned within 180 days of a transient ischemic attack or moderate stroke to undergo carotid artery stenting (n = 605) or carotid endarterectomy (n = 595). The primary end point was ipsilateral ischemic stroke or death 30 days after the procedure. A total of 1,183 patients were included in the analysis.

Results. The rate of the primary end point was 6.84% with stenting and 6.34% with endarterectomy. The study failed to prove the noninferiority of carotid artery stenting compared with carotid endarterectomy for the periprocedural complication rate. Results at 6 to 24 months are awaited.

The Carotid Revascularization Endarterectomy Versus Stenting (CREST) trial

Perhaps the most anxiously awaited results are those of the CREST trial,¹⁵ funded by the National Institutes of Health. This is a prospective, randomized, parallel, two-arm, multicenter clinical trial with blinded end point evaluation. Anticipated enrollment will include 2,500 patients. Patients are eligible for enrollment if they have symptoms of carotid stenosis within 180 days of a stroke or transient ischemic attack with ipsilateral carotid stenosis of at least 50% by angiography (70% by ultrasonography), or if they have asymptomatic carotid stenosis of at least 60% by angiography (70% by ultrasonography).

Patients are being randomized to undergo either carotid artery stenting or carotid endarterectomy. All receive aspirin as anti-platelet therapy, treatment for hypertension, and management of other stroke risk factors. Follow-up will last 4 years, with clinic visits at 1, 6, 12, 18, 24, 30, 36, 42, and 48 months. Primary outcome measures will be rates of death, stroke, or myocardial infarction at 30 days postoperatively, and ipsilateral stroke at 30 days postoperatively.

As of February 2007, 1,506 patients had been enrolled and 1,453 had been randomized at 94 sites in North America.

MEDICAID AND MEDICARE NOW PAY FOR THESE THERAPIES

An important practical consideration for patients and physicians is whether Medicaid and Medicare will pay for these therapies.

In July 2001, Medicare began to cover percutaneous transluminal angioplasty of the carotid artery with concurrent stent placement, when furnished in accordance with US Food and Drug Administration (FDA) protocols governing Category B (nonexperimental) investigational device exemption clinical trials.¹⁶ Angioplasty of the carotid artery, when provided solely for the purpose of carotid artery dilation concurrent with carotid stent placement, is considered to be a reasonable and necessary service when provided in the context of clinical trials.

In March 2005, Medicare began to provide coverage for percutaneous transluminal angioplasty of the carotid artery concurrent with the placement of an FDA-approved carotid stent with embolic protection for the following groups of patients:

• Those who would be at high risk during carotid endarterectomy and who also have symptomatic carotid artery stenosis of 70% or greater. Coverage is limited to procedures performed using FDA-approved carotid artery stenting systems and embolic protection devices.
• Those who would be at high risk during endarterectomy and who have symptomatic carotid artery stenosis of 50% to 70%, in accordance with the Category B Investigational Device Exemption clinical trials regulation, as a routine cost under the clinical trials policy, or in accordance with the national coverage determination on carotid artery stenting post-approval.
• Those who would be at high risk during carotid endarterectomy and have asymptomatic carotid artery stenosis greater than 80%, in accordance with the Category B Investigational Device Exemption clinical trials regulation, as a routine cost under the clinical trials policy, or in accordance with the national coverage determination on carotid artery stenting postapproval studies.

As noted above, Medicare and Medicaid will only cover carotid stenting if the stent system is FDA-approved, with concomitant use of a distal embolic protection device. However, in view of conflicting data from stenting trials to date, including EVA-3S¹³ and SPACE,¹⁴ it remains to be seen if emboli protection devices significantly reduce periprocedural stroke rates. The FDA recommends that if it is not technically possible to use one of these devices, then the procedure should be aborted due to safety issues.

These coverage decisions are an important practical aspect of carotid stenting and they should be familiar to physicians when they see and refer patients with carotid disease.