Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial

Abstract

Background: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.

Methods: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.

Findings: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197).

Interpretation: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.

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

Figure 1

Trial profile Data for the number of patients screened for eligibility were not recorded.

Figure 2

Time between randomisation and treatment Cumulative number of patients in whom allocated treatment was initiated per protocol plotted as a proportion of the total number randomised in each group (vertical axis), against the delay between the dates of randomisation and treatment (horizontal axis). Only allocated per-protocol treatment dates were counted.

Figure 3

Kaplan-Meier estimates of cumulative incidence of various outcome measures Data were analysed by intention to treat. The numbers above the end of the lines are the incidence estimates at 120 days after randomisation. HR=hazard ratio.

Figure 4

Subgroup analysis to compare the rates of stroke, death, or procedural myocardial infarction in different subgroups Subgroups are defined according to baseline characteristics and analysed by intention to treat up to 120 days after randomisation, apart from time from event to treatment, which is analysed per protocol. p values are associated with treatment-covariate interaction tests. *Data are number of events of first stroke, death, or procedural myocardial infarction within 120 days of randomisation/number of patients (Kaplan-Meier estimate at 120 days). †Patients with missing information were excluded from the analysis. ‡Time from the most recent ipsilateral event before randomisation to the date of treatment, analysed per protocol for 30-day procedural events only (results are relative risk and 95% CI at 30 days after treatment).

Figure 5

Meta-analysis comparing safety of carotid artery stenting with endarterectomy in the recent carotid stenting trials Odds ratio for any stroke, death, or procedural myocardial infarction within 30 days of treatment in the three recent trials of carotid artery stenting versus endarterectomy including only symptomatic patients. Analysis is based on published results of per-protocol data. The large diamond represents the odds ratio and 95% CI of the combined data. The summary estimate statistic was calculated by use of a Mantel-Haenszel fixed-effect model; the centre of the diamond is the point estimate, and its width the 95% CI. EVA-3S=Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis. SPACE=Stent-Protected Angioplasty versus Carotid Endarterectomy. ICSS=International Carotid Stenting Study.