Elsevier

The Lancet

Volume 361, Issue 9352, 11 January 2003, Pages 107-116
The Lancet

Articles
Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis

https://doi.org/10.1016/S0140-6736(03)12228-3Get rights and content

Summary

Background

Endarterectomy reduces risk of stroke in certain patients with recently symptomatic internal carotid stenosis. However, investigators have made different recommendations about the degree of stenosis above which surgery is effective, partly because of differences between trials in the methods of measurement of stenosis. To accurately assess the overall effect of surgery, and to increase power for secondary analyses, we pooled trial data and reassessed carotid angiograms.

Methods

We pooled data from the European Carotid Surgery Trial (ECST), North American Symptomatic Carotid Endarterectomy Trial, and Veterans Affairs trial 309 from the original electronic data files. Outcome events were re-defined, if necessary, to achieve comparability. Pre-randomisation carotid angiograms from ECST were re-measured by the method used in the other two trials.

Results

Risks of main outcomes in both treatment groups and effects of surgery did not differ between trials. Data for 6092 patients, with 35 000 patient-years of follow-up, were therefore pooled. Surgery increased the 5-year risk of ipsilateral ischaemic stroke in patients with less than 30% stenosis (n=1746, absolute risk reduction −2·2%, p=0·05), had no effect in patients with 30–49% stenosis (1429, 3·2%, p=0·6), was of marginal benefit in those with 50–69% stenosis (1549, 4·6%, p=0·04), and was highly beneficial in those with 70% stenosis or greater without near-occlusion (1095, 16·0%, p<0·001). There was a trend towards benefit from surgery in patients with near-occlusion at 2 years' follow-up (262, 5·6%, p=0·19), but no benefit at 5 years (−1·7%, p=0·9).

Interpretation

Re-analysis of the trials with the same measurements and definitions yielded highly consistent results. Surgery is of some benefit for patients with 50–69% symptomatic stenosis, and highly beneficial for those with 70% symptomatic stenosis or greater but without near-occlusion. Benefit in patients with carotid near-occlusion is marginal in the short-term and uncertain in the long-term.

Introduction

In the USA, the rate of carotid endarterectomy has more than doubled since the publication of positive results from large randomised controlled trials.1, 2, 3 Roughly 150 000 operations were done in 1998, about half of which were for recently symptomatic carotid stenosis.4, 5 Rates of endartectomy have also risen in Europe.6

There have been five randomised trials of endarterectomy for recently symptomatic carotid stenosis.1, 2, 7, 8, 9 The first two were small, were done more than 20 years ago, included a high proportion of patients with non-carotid symptoms, and did not stratify results by severity of stenosis.8, 9 In 1991, the Veterans Affairs trial (VA309) reported a non-significant trend in favour of surgery,7 but was stopped early when the initial results of the two largest trials, the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET), were reported.10, 11 The final results of these trials were published in 1998.1, 2 The ECST investigators reported benefit from surgery only in patients with 80% stenosis or greater, and in women with 90% stenosis or greater.1 Clinical guidelines in Europe are based on these results.6, 12 By contrast, the NASCET findings showed significant benefit from surgery in patients with 50% stenosis or greater,2 and North American guidelines are based on these results.13, 14

The differences between the trial results are partly due to differences in the methods of measurement of the degree of carotid stenosis on the prerandomisation catheter angiograms;15 the method used in ECST produces higher values than that used in NASCET and VA309 (figure 1).16, 17 The definitions of outcome events also differed. Meta-analyses of the overall trial results have been reported,18, 19 but these took no account of the differences between the trials. Only by detailed re-analysis of the individual patient data and reassessment of the original angiograms can the results be properly compared or combined.

Our aim was to determine with as much precision as possible the effectiveness and durability of endarterectomy by degree of carotid stenosis. We therefore pooled data for individual patients from the three trials, reassessed the original angiograms, and did analyses with the same method of measurement of stenosis and the same definitions of outcomes.

Section snippets

Methods

Searches for randomised controlled trials of endarterectomy plus medical treatment versus medical treatment alone for symptomatic carotid stenosis18, 19, 20 identified only five trials.1, 2, 7, 8, 9 Since the two small, early trials no longer accord with current clinical practice,8, 9 data from the three most recent trials (ECST, NASCET, and VA309) were used.1, 2, 7 These data consisted of all patients randomised in the past 20 years, which were more than 95% of patients ever randomised.

Results

Because of remeasurements of the degree of carotid stenosis and specific other baseline clinical characteristics, and changes in definitions of outcome events, the data we obtained differ slightly from those in the original trial reports. Individual patient data were available for all 6092 patients randomised and included in the final analysis of the three original trials (table 1). Of these, one VA309 patient had no follow-up data at the time the trial was stopped, nine ECST patients had an

Discussion

Analysis of individual patient data has advantages over meta-analysis of overall trial results, and was essential for the endarterectomy trials. Differences between the trials in the method of measurement of carotid stenosis and in the definition of outcome events made tabular results impossible to combine satisfactorily. By re-analysis of the individual patient data and reassessment of the carotid angiograms we have shown that the results of ECST and NASCET were consistent, removing the

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