Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial

Abstract

Background: Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments.

Methods: Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470.

Findings: 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0-5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72-1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28-2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02-2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups.

Interpretation: Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis.

Funding: Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

Figure 1

Trial profile Numbers at screening and excluded before enrolment were not recorded. ITT=intention to treat. *Excluded from the restenosis analysis. † Excluded from per-protocol analysis and restenosis analysis. ‡Excluded from per-protocol analysis.

Figure 2

Kaplan-Meier estimates of cumulative incidence for major outcomes (A) Fatal or disabling stroke. (B) Any stroke. (C) Procedural stroke or procedural death or ipsilateral stroke during follow-up. (D) All-cause death. (E) Any stroke more than 30 days after treatment. (F) Ipsilateral stroke more than 30 days after treatment. (G) Contralateral carotid or vertebrobasilar stroke more than 30 days after treatment. (H) Ipsilateral severe (at least 70%) carotid stenosis after completed treatment, generated by life-table analysis. Panels A–D show results for the intention-to-treat population, E–G for the per-protocol population from 30 days after treatment, and H for the per-protocol population from treatment. Percentage values are the estimated cumulative incidence at 1 year and 5 years. Graphs stop at 7 years' follow-up because numbers beyond that time were less than 100, but analyses were based on all follow-up data (maximum 10 years). HR=hazard ratio. CAS=carotid stenting. CEA=carotid endarterectomy.

Figure 3

Functional ability measured by the modified Rankin scale at the end of follow-up* A permutation test was done to compare scores at the end of follow-up between the two groups: unadjusted, p=0·49; adjusted for baseline modified Rankin scale score, p=0·24. CAS=carotid stenting. CEA=carotid endarterectomy. *Excludes seven patients (three CAS and four CEA) who had no scores recorded during follow-up and were still alive at their final visit.