A Systematic Review of Randomized Controlled Trials of Carotid Endarterectomy for Symptomatic Carotid Stenosis
- best medical treatment
- carotid endarterectomy
- degree of stenosis
- symptomatic carotid stenosis
- timing to surgery
Severe narrowing (stenosis) of the carotid artery is an important cause of stroke. Surgical treatment (carotid endarterectomy) may reduce the risk of stroke but carries a risk of operative complications.
The objective of this review was to determine the balance of benefit versus risk of endarterectomy plus best medical management in patients with recently symptomatic (transient ischemic attack or nondisabling stroke) carotid stenosis compared with best medical management alone.1
We searched the Cochrane Stroke Group Trials Register (July 2010), MEDLINE (1966 to March 2010), EMBASE (1990 to March 2010), and 3 other databases and hand-searched relevant journals and reference lists.
Randomized controlled trials comparing “best medical treatment plus endarterectomy” with “best medical therapy” in patients with carotid stenosis and a recent transient ischemic attack or nondisabling ischemic stroke in the territory of that artery.
Data Collection and Analysis
Two reviewers independently selected the studies and extracted the data.
There have been 5 randomized trials of endarterectomy for recently symptomatic carotid stenosis, but the first 2 trials were small, performed >30 years ago, included a high proportion of patients with noncarotid symptoms, and did not stratify results by severity of stenosis. Only the 3 trials were therefore included: North American Symptomatic Carotid Endarterectomy Trial (NASCET); European Carotid Surgery Trial (ECST); and Veterans Affairs trial (VACSP). However, these trials still differed in the methods of measurement of carotid stenosis and also in the definition of stroke such that a standard meta-analysis of published results would not be valid. We therefore did a pooled analysis of individual patient data. Outcome events were redefined, where necessary, to achieve comparability, and the prerandomization ECST carotid angiograms were remeasured by the method used in NASCET and VACSP.
On reanalysis, there were no statistically significant differences between the trials in the risks of any of the main outcomes in either of the treatment groups or in the effects of surgery. Data on the 6092 patients from the 3 trials, with 35 000 patient-years of follow-up, were therefore pooled. Surgery increased the 5-year risk of ipsilateral ischemic stroke in patients with <30% stenosis (n=1746; absolute risk reduction, −2.2%; P=0.05), had no significant effect in patients with 30% to 49% stenosis (n=1429; absolute risk reduction, 3.2%; P=0.6), was of marginal benefit in patients with 50% to 69% stenosis (n=1549; absolute risk reduction, 4.6%; P=0.04), and was highly beneficial in patients with 70% to 99% stenosis without near occlusion (n=1095; absolute risk reduction, 16.0%; P<0.001). However, there was no evidence of benefit (n=262; absolute risk reduction, −1.7%; P=0.9) in patients with near occlusions.
In the pooled data from ECST and NASCET, the risk of ipsilateral carotid territory ischemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to 7 predefined and 7 post hoc subgroups. Sex (P=0.003), age (P=0.03), and time from the last symptomatic event to randomization (P=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged ≥75 years, and patients randomized within 2 weeks after their last ischemic event and fell rapidly with increasing delay. For patients with 50% to 99% stenosis (NASCET method), the number of patients needed to undergo surgery to prevent 1 ipsilateral stroke in 5 years was 9 for men versus 36 for women, 5 for age >75 years versus 18 for age <65 years, and 5 for patients randomized within 2 weeks after their last ischemic event versus 125 for patients randomized >12 weeks. These observations were consistent across the individual trials.
Implication for Practice
Endarterectomy is of some benefit for 50% to 69% symptomatic stenosis and highly beneficial for 70% to 99% stenosis without near occlusion. Benefit in patients with carotid near occlusion is marginal in the short term and uncertain in the long term. These results are generalizable only to surgically fit patients operated on by surgeons with low complication rates (<7% risk of stroke and death). Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other factors, including the delay to surgery after the presenting event. In particular, in patients with only 50% to 69% stenosis, there was no evidence of benefit in women and little evidence of benefit if surgery was delayed by >2 weeks after the presenting event.
This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2011, Issue 4. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review (http://dx.doi.org/10.1002/14651858.CD001081).
Sources of Funding
This Cochrane Review was supported as a part of the Department of Health (England) Cochrane Review Incentive Scheme.
- Received June 7, 2011.
- Revision received June 11, 2011.
- Accepted June 24, 2011.
- © 2011 American Heart Association, Inc.