Elsevier

The Lancet

Volume 363, Issue 9413, 20 March 2004, Pages 915-924
The Lancet

Articles
Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery

https://doi.org/10.1016/S0140-6736(04)15785-1Get rights and content

Summary

Background

Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery.

Methods

We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups.

Results

5893 patients with 33 000 patient-years of follow-up were analysed. Sex (p=0·003), age (p=0·03), and time from the last symptomatic event to randomisation (p=0·009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials.

Interpretation

Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.

Introduction

Carotid endarterectomy is one of the most common vascular surgical procedures,1, 2, 3 and it reduced the risk of ischaemic stroke in patients with recently symptomatic carotid stenosis in two large randomised controlled trials.4, 5 A smaller trial, the Veterans Affairs trial (VA309)6 was stopped early when investigators in the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET) reported their initial findings.7, 8 In 1998, the final results of the ECST and NASCET were reported, and the investigators made different recommendations about the degree of stenosis above which surgery was effective.1, 2 However, there were important differences between the trials in the method of measurement of carotid stenosis on the prerandomisation angiograms and in the definitions of outcome events.9, 10, 11 Subsequent analysis after remeasurement of the ECST angiograms by the method used in NASCET, and use of the definition of stroke as any cerebral or retinal event with symptoms lasting longer than 24 h, yielded results that were highly consistent with NASCET.12

A recent meta-analysis of individual patients' data from the ECST, NASCET, and VA309, using the same method of measurement of stenosis and definitions of outcome events, showed that surgery was harmful in patients with less than 30% stenosis, of no benefit in those with 30–49% stenosis, of some benefit for 50–69% stenosis, and highly beneficial for those with 70% or more stenosis without near-occlusion.13 However, there are several other factors that might affect the risks and benefits of surgery, including the delay between presentation of symptoms and surgery, and specific clinical and angiographic characteristics,14, 15, 16, 17, 18, 19, 20, 21 but neither ECST nor NASCET had high enough statistical power to determine the effect of surgery in subgroups. We therefore analysed pooled individual patients' data from these two trials to determine the effect of surgery in relation to seven predefined and seven post hoc clinical and angiographical subgroups.

Section snippets

Eligibility criteria

Criteria for inclusion of trials, and methods of data pooling and analysis have been reported previously.13 Two small early trials were excluded because the methods were not consistent with current clinical practice.22, 23 VA309 was not included in the present study because the trial was confined to men, and several other subgroup variables were unavailable for analysis. The remaining large trials ECST and NASCET included 95% of patients ever randomised to endarterectomy versus medical

Results

Data for individual patients were available for all 5903 patients included in the final analysis of the ECST and NASCET. Of these, nine ECST patients had an occlusion of the symptomatic carotid artery on the prerandomisation angiogram, and the degree of stenosis was unknown in one ECST patient. These cases were excluded from our analyses, leaving 5893 (99·8%) patients. Mean follow-up was 66 months (SD 34, range 1day to 166 months), giving a total of 33 000 patient-years of follow-up.

Table 1

Discussion

We found three significant and clinically important subgroup treatment effect modifiers in the predefined subgroup variables. Benefit from surgery was greater in men than in women, and in the elderly, and benefit decreased with time since last symptoms. These observations were consistent across the 50–69% and 70% or more stenosis groups and across the two trials. Taken with other evidence discussed later, we feel that these subgroup observations are sufficiently robust to be used to guide the

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