Absence of large-scale trial data, perceived limitations plague carotid stenting

SAN FRANCISCO — While the use of carotid artery stenting in carotid revascularization procedures has steadily increased over the past decade, there have been few large randomized trials initiated to assess the efficacy and long-term outcomes compared with carotid endarterectomy. This may further impede its clinical application, according to presenters at TCT 2013.

Alison Halliday, MD, from the University of Oxford, United Kingdom, reviewed three trials currently underway — including CREST-2, SPACE-2 and ACST-2 — that are expected to contribute to the absence of large trial data needed to validate carotid artery stenting (CAS).

To evaluate whether intensive medical therapy is an acceptable alternative to carotid endarterectomy (CEA) or CAS, the planned CREST-2 trial will randomize 2,050 patients to two arms: CAS plus medical therapy or CEA plus medical therapy vs. medical therapy alone. The primary endpoint will be any stroke or death during the periprocedural period and ipsilateral stroke thereafter, up to 4 years of follow-up.

The SPACE-2 trial, conducted in Germany, Austria and Switzerland, initially tried a more complex trial design involving a three-arm randomization: medical therapy (20%) vs. revascularization, with the revascularization then subrandomized between CAS (40%) and CEA (40%). However, due to small patient numbers, the SPACE-2 trial was redesigned with a similar construct as CREST-2, Halliday said.

In collaboration with the other two trials, the ongoing ACST-2 trial (current enrollment, 1,300 patients) is comparing CEA vs. CAS in patients with asymptomatic carotid stenosis where there is significant clinical uncertainty as to which treatment is more appropriate.

“The idea is to get randomized trials comparing all three of these medical procedures, but no trial can successfully compare all of these in one,” Halliday said. “We are trying to emphasize the need for collaboration … to achieve a proper meta-analysis of over 5,000 patients by 2019 with decent follow-up to 2025.”

Validation of data

In another presentation, Sumaira Macdonald, MD, PhD, of Freeman Hospital, Newcastle upon Tyne, United Kingdom, discussed some of the overall limitations of CAS and questioned whether the procedure is clinically meaningful in the absence of large-scale trial data compared with CEA.

In the original CREST trial, 2,502 patients with symptomatic or asymptomatic carotid stenosis were randomized to receive either CEA or CAS. While there was no difference between the two groups in the estimated 4-year rates of the primary endpoint (composite of periprocedural stroke, MI, or death, or the incidence of ipsilateral stroke ≤4 years), stenting was found to carry a higher risk for stroke and surgery a higher risk for MI.

Another prevailing limitation of CAS, according to Macdonald, was seen in the International Carotid Stenting Study published in Lancet Neurology. Fifty percent of patients in the stenting group and 17% of patients in the surgery group exhibited at least one new diffusion-weighted imaging lesion detected on post-treatment MRI scans done a median of 1 day after treatment (adjusted OR=5.21; 95% CI, 2.78-9.79; P<.0001).

For more information:

Halliday A. Carotid stenting randomized trials redux: ACST2, SPACE 2 and CREST 2.

Macdonald S. New devices and techniques in carotid stenting: Clinically meaningful? Both presented at: TCT 2013; Oct. 27-Nov. 1, 2013; San Francisco.

Disclosure: Halliday reports no relevant financial disclosures. Macdonald reports conflicts of interest with several device and pharmaceutical companies.