Elsevier

The Lancet

Volume 363, Issue 9420, 8 May 2004, Pages 1491-1502
The Lancet

Articles
Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial

https://doi.org/10.1016/S0140-6736(04)16146-1Get rights and content

Summary

Background

Among patients with substantial carotid artery narrowing but no recent neurological symptom (stroke or transient ischaemia), the balance of surgical risks and longterm benefits from carotid endarterectomy (CEA) was unclear.

Methods

During 1993–2003, 3120 asymptomatic patients with substantial carotid narrowing were randomised equally between immediate CEA (half got CEA by 1 month, 88% by 1 year) and indefinite deferral of any CEA (only 4% per year got CEA) and were followed for up to 5 years (mean 3·4 years). Kaplan-Meier analyses of 5-year risks are by allocated treatment.

Findings

The risk of stroke or death within 30 days of CEA was 3·1% (95% Cl 2·3–4·1). Comparing all patients allocated immediate CEA versus all allocated deferral, but excluding such perioperative events, the 5-year stroke risks were 3·8% versus 11% (gain 7·2% [95% Cl 5·0–9·4], p<0·0001). This gain chiefly involved carotid territory ischaemic strokes (2·7% vs 9·5%; gain 6·8% [4·8–8·8], p<0·0001), of which half were disabling or fatal (1·6% vs 5·3%; gain 3·7% [2·1–5·2], p<0·0001), as were half the perioperative strokes. Combining the perioperative events and the non-perioperative strokes, net 5-year risks were 6·4% versus 11·8% for all strokes (net gain 5·4% [3·0–7·8], p<0·0001), 3·5% versus 6·1% for fatal or disabling strokes (net gain 2·5% [0·8–4·3], p=0·004), and 2·1% versus 4·2% just for fatal strokes (net gain 2·1% [0·6–3·6], p=0·006). Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or (apart from the importance of cholesterol) in the long-term postoperative benefits. These benefits were separately significant for males and females; for those with about 70%, 80%, and 90% carotid artery narrowing on ultrasound; and for those younger than 65 and 65–74 years of age (though not for older patients, half of whom die within 5 years from unrelated causes). Full compliance with allocation to immediate CEA or deferral would, in expectation, have produced slightly bigger differences in the numbers operated on, and hence in the net 5-year benefits. The 10-year benefits are not yet known.

Interpretation

In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70% or more on ultrasound (many of whom were on aspirin, antihypertensive, and, in recent years, statin therapy), immediate CEA halved the net 5-year stroke risk from about 12% to about 6% (including the 3% perioperative hazard). Half this 5-year benefit involved disabling or fatal strokes. But, outside trials, inappropriate selection of patients or poor surgery could obviate such benefits.

Introduction

Patients with substantial (eg, 60–99%) carotid artery narrowing are at increased risk of suffering a disabling or fatal ischaemic stroke in the carotid territory of the brain. The hazard is greater if they are already symptomatic (ie, have recently suffered some relevant neurological symptom, such as stroke or transient cerebral or retinal ischaemia) in the parts of the brain supplied by the carotid arteries (the carotid territory). Carotid endarterectomy (CEA) can remove arterial narrowing, but the surgical procedure itself involves some immediate risk of perioperative death or stroke. Moreover, even successful CEA might not permanently eliminate all thromboembolic risk. Hence, the balance of risk and long-term benefit is uncertain, particularly for fatal and disabling strokes.

Several major randomised trials of CEA, some in symptomatic1, 2 and some in asymptomatic3, 5 (those who have had no relevant neurological symptoms) patients, have attempted to address the net effects of CEA on the risks of suffering a major stroke. In 1991, the European and North American carotid surgery trials (ECST1 and NASCET2) demonstrated the net long-term benefits of CEA for symptomatic patients with severe carotid artery narrowing. There has remained, however, much uncertainty about the net benefits of CEA for asymptomatic patients, despite promising results in 1993 and 1995 from two US trials (VA3 and ACAS5), which showed significant reductions in the incidence of transient cerebral ischaemia3 or non-disabling stroke,5 but not of fatal or disabling stroke.

The international Asymptomatic Carotid Surgery Trial (ACST)4 was set up in 1993 with the aim of being large enough (and, eventually, having long enough follow-up) to assess the net long-term effects of CEA on overall stroke risk and on fatal or disabling stroke among patients with substantial carotid artery narrowing, but with no relevant neurological symptoms in the previous 6 months. Randomisation in ACST ended after 10 years, but long-term follow-up will continue for several more years. The present report of the ACST results describes the hazards and the medium-term benefits of CEA (analysed both separately and together) during just the first 5 years after randomisation.

Section snippets

Methods

ACST is a multicentre randomised trial among asymptomatic patients with substantial carotid artery narrowing, comparing immediate CEA versus deferral of any CEA until a definite indication was thought to have arisen. All other aspects of the management of the patients were left to the discretion of the clinician, and usually included antiplatelet therapy, antihypertensive treatment, and, in recent years, lipid-lowering therapy.

Results

3120 patients were randomised between April, 1993, and July, 2003, from 126 centres in 30 countries. 1560 were allocated to immediate CEA and 1560 to deferral of any CEA (figure 1). Because minimised randomisation8 was used, there are no significant differences between the initial characteristics of the two groups (see below).

Discussion

Because ACST involves large numbers of patients, its 5-year overall findings for stroke prevention are clear. Among patients up to 75 years of age with severe carotid stenosis on ultrasound but no relevant neurological symptoms, CEA approximately halved the net 5-year risk of stroke. These results include the 3% perioperative hazard. Almost all the gain involved carotid territory ischaemic strokes, of which half were disabling or fatal.

The only other large trial, ACAS, involved similar patients

References (18)

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