Editor's Choice – Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials

Urs Fisch,Stefanie Von Felten,Andrea Wiencierz,Olav Jansen,George Howard,Jeroen Hendrikse,Alison Halliday,Gustav Fraedrich,Hans-Henning Eckstein,David Calvet,Richard Bulbulia,Jean-Pierre Becquemin,Ale Algra,Peter Rothwell,Peter Ringleb,Jean-Louis Mas,Martin M Brown,Thomas G Brott,Leo H Bonati

doi:10.1016/j.ejvs.2021.02.024

Abstract

Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2= 6.58, p= .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p= .019). Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Highlights

Patients with recently symptomatic carotid artery stenosis are at high risk of stroke.[1,2] Earlier randomised controlled trials (RCTs), conducted in the 1980s and 1990s, demonstrated a reduction in stroke risk by revascularisation by carotid endarterectomy (CEA) when compared with medical therapy alone.3e5 Pooled analysis of two of these trials suggested that the benefit of CEA was highest when performed early after the qualifying ischaemic event.[6]
The early risk of stroke under medical therapy was analysed in patients with symptomatic carotid stenosis awaiting revascularisation in recent RCTs.9e12 The cumulative stroke risk was 2% at 120 days and was higher among patients that were randomised shortly after the qualifying event
The risk of stroke was lower in these recent trials than it was among patients treated medically in earlier trials3e5 when the comparison was adjusted for important patient characteristics differing between trials

Summary

Introduction

Patients with recently symptomatic carotid artery stenosis are at high risk of stroke.[1,2] Earlier randomised controlled trials (RCTs), conducted in the 1980s and 1990s, demonstrated a reduction in stroke risk by revascularisation by carotid endarterectomy (CEA) when compared with medical therapy alone.3e5 Pooled analysis of two of these trials suggested that the benefit of CEA was highest when performed early after the qualifying ischaemic event.[6] Current guidelines recommend revascularisation within two weeks of initial symptoms.[7,8]. The risk of early stroke was studied in patients with symptomatic carotid stenosis recruited in four more recent RCTs,9e12 which compared revascularisation by carotid artery stenting (CAS) vs CEA. The aim was to assess the risk of stroke under medical therapy occurring between randomisation and revascularisation in these recent trials, to identify its predictors, and to compare this risk with the risk of early stroke among medically treated patients in earlier trials, which compared medical therapy vs. CEA

Methods

Results

Conclusion