Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data

Summary

Background

Results from randomised controlled trials have shown a higher short-term risk of stroke associated with carotid stenting than with carotid endarterectomy for the treatment of symptomatic carotid stenosis. However, these trials were underpowered for investigation of whether carotid artery stenting might be a safe alternative to endarterectomy in specific patient subgroups. We therefore did a preplanned meta-analysis of individual patient data from three randomised controlled trials.

Methods

Data from all 3433 patients with symptomatic carotid stenosis who were randomly assigned and analysed in the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS) were pooled and analysed with fixed-effect binomial regression models adjusted for source trial. The primary outcome event was any stroke or death. The intention-to-treat (ITT) analysis included all patients and outcome events occurring between randomisation and 120 days thereafter. The per-protocol (PP) analysis was restricted to patients receiving the allocated treatment and events occurring within 30 days after treatment.

Findings

In the first 120 days after randomisation (ITT analysis), any stroke or death occurred significantly more often in the carotid stenting group (153 [8·9%] of 1725) than in the carotid endarterectomy group (99 [5·8%] of 1708, risk ratio [RR] 1·53, [95% CI 1·20–1·95], p=0·0006; absolute risk difference 3·2 [1·4–4·9]). Of all subgroup variables assessed, only age significantly modified the treatment effect: in patients younger than 70 years (median age), the estimated 120-day risk of stroke or death was 50 (5·8%) of 869 patients in the carotid stenting group and 48 (5·7%) of 843 in the carotid endarterectomy group (RR 1·00 [0·68–1·47]); in patients 70 years or older, the estimated risk with carotid stenting was twice that with carotid endarterectomy (103 [12·0%] of 856 vs 51 [5·9%] of 865, 2·04 [1·48–2·82], interaction p=0·0053, p=0·0014 for trend). In the PP analysis, risk estimates of stroke or death within 30 days of treatment among patients younger than 70 years were 43 (5·1%) of 851 patients in the stenting group and 37 (4·5%) of 821 in the endarterectomy group (1·11 [0·73–1·71]); in patients 70 years or older, the estimates were 87 (10·5%) of 828 patients and 36 (4·4%) of 824, respectively (2·41 [1·65–3·51]; categorical interaction p=0·0078, trend interaction p=0·0013].

Interpretation

Stenting for symptomatic carotid stenosis should be avoided in older patients (age ≥70 years), but might be as safe as endarterectomy in younger patients.

Funding

The Stroke Association.

Introduction

In patients with recently symptomatic carotid stenosis, carotid endarterectomy reduces the risk of further stroke.1, 2 In the past few years, endovascular treatment with placement of a stent has emerged as an alternative to carotid endarterectomy. Outcomes after stenting were not worse than those after endarterectomy in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial,³ in which the two procedures were compared in patients with increased surgical risk, who also mostly had asymptomatic carotid stenosis. By contrast, results from several large trials in patients with symptomatic carotid stenosis who were judged to be at standard surgical risk—the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS)—have shown a higher periprocedural risk of stroke with stenting than with endarterectomy.4, 5, 6 Nevertheless, important questions have remained unanswered: differences between definitions of primary short-term outcome measures and wide confidence intervals for the treatment effects in some trials render accurate assessment of the excess risk posed by stenting difficult. More importantly, periprocedural risks of stenting and endarterectomy vary with patient characteristics.7, 8, 9, 10 Outcomes might therefore be similar between the two procedures in specific groups of patients, but no trial was large enough to establish the balance of stenting and endarterectomy in any patient subgroup with an acceptable degree of certainty.

The investigators of the EVA-3S, SPACE, and ICSS studies set up the Carotid Stenting Trialists' Collaboration (CSTC) with the purpose of doing a preplanned meta-analysis of individual patient data from these trials. The main objectives were, first, to provide an accurate estimate of the risk ratio of major outcome events with stenting and endarterectomy in patients with symptomatic carotid stenosis; and second, to compare the safety and efficacy of these two procedures in predefined subgroups of patients. Here, we report the main results of the pooled analysis of the short-term outcome.