Stent-Protected Angioplasty Versus Carotid Endarterectomy - SPACE: 30-Day and 2-Year Results

Sep 19, 2008
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Trial Sponsor:
Federal Ministry of Education and Research; German Research Foundation; The German Society of Neurology; The German Society of Neuroradiology; The German Radiological Society; Boston Scientific; Guidant; Sanofi-Aventis.
Date Published:
01/01/2006
Date Updated:
09/19/2008
Original Posted Date:
09/19/2008
References

Description:

The goal of the trial was to evaluate whether carotid artery stenting (CAS) was noninferior to carotid endarterectomy (CEA) among patients with symptomatic carotid artery stenosis.

Hypothesis:

CAS will be noninferior to CEA.

Study Design

Study Design:

Patients Enrolled: 1,200
Mean Follow Up: 2 years
Mean Patient Age: 68 years
Female: 28

Patient Populations:

  • Symptomatic stenosis (amaurosis, TIA, or stroke) of carotid bifurcation or internal carotid artery in the prior 180 days
  • Modified Rankin scale score ≤3
  • Severe ipsilateral carotid artery stenosis
  • Age >50 years

Primary Endpoints:

Ipsilateral ischemic stroke or death through 30 days, evaluated for noninferiority

Secondary Endpoints:

  • Death or disabling ipsilateral stroke
  • Any stroke
  • Procedural failure including inability to treat using the randomized technique, remaining stenosis of ≥50% on ultrasound at a follow-up visit, or vessel occlusion through 30 days
  • Stroke or death at 2 years
  • Death at 2 years
  • Stroke between 31 days and 2 years

Drug/Procedures Used:

Patients with symptomatic carotid artery stenosis were randomized to CAS (n = 605) or CEA (n = 595). Use of protection devices, predilation, and balloon size was at the discretion of the interventional physician. Patients were followed for 2 years.

Concomitant Medications:

Aspirin (100 mg) and clopidogrel (75 mg) for at least 3 days prior to and 30 days following the procedure in the CAS group; aspirin 100 mg in the CEA group

Principal Findings:

The most frequent qualifying events were transient ischemic attack (TIA) in 30% of patients, stroke in 44% of patients, and multiple events in 9% of patients. Stenosis severity was 60-69% in 22% of patients, 70-79% in 9% of patients, and 80-89% in 34% of patients. Embolic protection devices were used in 27% of patients who received stents in the CAS group.

The primary endpoint of death or ipsilateral strokes occurred in 6.84% of the CAS group and 6.34% of the CEA group, an absolute difference of 0.51% (90% confidence interval [CI] 1.89%-2.91%), failing to meet the noninferiority criteria of the trial (p = 0.09). Results in the per protocol analysis also failed to meet the noninferiority criteria (6.95% for CAS vs. 5.64% for CEA, absolute difference of 1.32%).

Most secondary endpoints fell in favor of CEA, including disabling ipsilateral stroke or death (4.67% for CAS vs. 3.77% for CEA, odds ratio [OR] 1.25, 95% CI 0.71–2.22); disabling ipsilateral stroke (4.01% for CAS vs. 2.91% for CEA, OR 1.39, 95% CI 0.74–2.62); any stroke (7.51% for CAS vs. 6.16% for CEA, OR 1.24, 95% CI 0.79–1.95); death (0.67% for CAS vs. 0.86% for CEA, p = ns) and procedural failure (3.17% for CAS vs. 2.05% for CEA, OR 1.56, 95% CI 0.71–3.56). Results were similar in several subgroups, including those treated with embolic protection devices in the CAS group.

At 2 years, ipsilateral stroke (plus any stroke or death within 30 days) occurred in 9.5% of the CAS group versus 8.8% of the CEA group (p = 0.62). Similarly, all-cause mortality was 6.3% vs. 5.0% (p = 0.68) and ipsilateral ischemic strokes between 31 days and 2 years were 2.2% versus 1.9% (p = ns), respectively. Recurrent stenosis of at least 70% occurred in 10.7% of the CAS group versus 4.6% of the CEA group (p = 0.0009).

Interpretation:

Among patients with symptomatic carotid artery stenosis, treatment with CAS failed to demonstrate noninferiority compared with CEA at 30-day follow-up.

In addition to failing to meet the noninferiority criteria on the primary endpoint in both the intent-to-treat analysis and the per-protocol analysis, all secondary endpoints fell in favor of CEA over CAS. Additionally, use of embolic protection devices did not appear to alter the results.

By 2 years, the incidence of stroke and death was similar between the treatment groups. There was significantly more restenosis detected by ultrasound in the CAS group. Although the SPACE study results were inconclusive at 30 days, long-term follow-up shows similar clinical outcomes between these two treatment modalities. The impact of late restenosis needs to be determined.

References:

Eckstein HH, Ringleb P, Allenberg JR, et al. Results of the stent-protected angioplasty versus carotid endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial. Lancet Neurol 2008;7:893-902.

The SPACE Collaborative Group. 30-day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet 2006;368(9543):1239-47.

Keywords: Odds Ratio, Stroke, Follow-Up Studies, Embolic Protection Devices, Ischemic Attack, Transient, Endarterectomy, Carotid, Blindness, Constriction, Pathologic, Confidence Intervals, Carotid Stenosis, Carotid Artery, Internal, Stents


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