News | SPACE and EVA-3S: CAS fails to meet criteria for non-inferiority in comparison with CEA | Which Medical Device

Results from the Stent-Supported Percutaneous Angioplasty of the Carotid Artery vs Endarterectomy (SPACE) trial and the Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S), showed that carotid stenting failed to meet criteria for non-inferiority versus endarterectomy, and showed slightly higher rates of ipsilateral ischaemic stroke and death at 30 days.

However, longer-term follow-up of both trials, presented at last year's European Stroke Conference (2009), showed rates of ipsilateral stroke were low and similar between carotid stenting and endarterectomy groups at two and four years of follow-up.

According to SPACE investigator Dr Peter A Ringleb, rom Ruprecht-Karls-University, Heidelberg, Germany, “The conclusion from the SPACE trial is exactly the same as the EVA-3S study; that is, if a patient has been treated successfully without any complications, the [long-term] risk of a secondary stroke is very small and very comparable between these two modalities.”

SPACE Trial

The SPACE trial was a multi-national, prospective randomised study that aimed to test the hypothesis that CAS was not inferior to CEA for the treatment of patients with severe symptomatic carotid stenosis of >70%. A total of 1,214 patients were randomised to carotid angioplasty with stenting (n=613) or CEA (n=601). Thirty-day results from this trial did not prove non-inferiority of CAS compared with CEA.

Two-year results showed that in both intention-to-treat (ITT) and per-protocol analyses, Kaplan-Meier estimates of ipsilateral ischaemic stroke up to two years after the procedure and any periprocedural stroke or death were similar between the groups.

It was reported that restenosis of 70% or greater was significantly more common in the stenting group, again in both ITT and per-protocol analyses. However, only two cases of restenosis were associated with neurological symptoms, the authors noted. Although the incidence of restenosis was higher, they add, “it cannot be excluded that the degree of in-stent stenosis is slightly overestimated by conventional ultrasound criteria.”

The authors concluded, “Patients who were successfully treated with stent-protected angioplasty had a similar low risk of secondary cerebrovascular events as patients who were treated with endarterectomy, indicative of the similar preventive ability of endarterectomy and carotid angioplasty with stenting.” They added, “To assess the long-term effects, and particularly the effect of restenosis, most investigators agreed to collect follow-up data for up to five years after the initial study protocol had ended.”

EVA-3S

The EVA-3S trial was also a randomised non-inferiority trial comparing CAS with CEA in 527 patients with carotid stenosis of 60% or more that had recently become symptomatic. The trial was stopped early due to a higher risk of any stroke or death within 30 days of the procedure, and the main results published within a week of those of the SPACE trial in 2006.

In a recent paper, the EVA-3S investigators, with lead author Dr Jean-Louis Mas, Hôpital Sainte-Anne, Paris, France, reported on follow-up of these patients out to four years. They found that the cumulative probability of periprocedural stroke or death and non-procedural ipsilateral stroke was still higher among those in the stenting group versus endarterectomy.

However, the authors explained that a hazard function analysis showed that the differences in cumulative outcomes between stenting and endarterectomy were largely accounted for by events that occurred within 30 days of the original procedure. They explained, “After the periprocedural period, the risk of ipsilateral stroke was low and similar in both treatment groups.”

To conclude, the authors stated, “The safety of carotid stenting needs to be improved before it can become a widespread alternative to carotid endarterectomy in patients with symptomatic carotid stenosis.”