Abstract: We included three trials involving 6343 participants. As the trials differed in the methods of measurement of carotid stenosis and in the definition of stroke, we did a pooled analysis of individual patient data on 6092 participants (35,000 patient years of follow-up), after reassessing the carotid angiograms and outcomes from all three trials using the primary electronic data files, and redefined outcome events where necessary, to achieve comparability. On re-analysis, there were no 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. Surgery increased the five-year risk of ipsilateral ischaemic stroke in participants with less than 30% stenosis (N = 1746, risk ratio (RR) 1.27, 95% confidence interval (CI) 0.80 to 2.01), had no significant effect in participants with 30% to 49% stenosis (N = 1429, RR 0.93, 95%CI 0.62 to 1.38), was of benefit in participants with 50% to 69% stenosis (N = 1549, RR 0.84, 95%CI 0.60 to 1.18), and was highly beneficial in participants with 70% to 99% stenosis without near-occlusion (N = 1095, RR 0.47, 95%CI 0.25 to 0.88). However, there was no evidence of benefit (N = 271, RR 1.03, 95%CI 0.57 to 1.84) in participants with near-occlusions. Ipsilateral ischaemic stroke describes insufficient blood flow to the cerebral hemisphere, secondary to same side severe stenosis of the internal carotid artery. Endarterectomy was of some benefit for participants with 50% to 69% symptomatic stenosis (moderate-quality evidence), and highly beneficial for those with 70% to 99% stenosis without near-occlusion (moderate-quality evidence). We found no benefit in people with carotid near-occlusion (high-quality evidence).

Plain-language summary: This review identified three randomised controlled trials (6343 participants randomised), which compared carotid surgery with no carotid surgery (i.e. best medical therapy plus surgery versus best medical therapy alone) in participants with carotid stenosis and recent transient ischaemic attacks (TIA) or minor ischaemic strokes in the territory of that artery. The trials were carried out in Europe, USA, and Canada and included some centres in Israel, South Africa, and Australia. The gender ratio of participants was 2.6:1 (72% men and 28% women); 90% of participants were younger than 75 years old. The results of the three trials were initially conflicting because they differed in how they measured carotid stenosis and how they defined the outcomes. To address this discrepancy, we reassessed the patient data using the same methods and definitions, so results could be compared. The results of the review are current up to July 2016. Results showed that older male participants with 70% to 99% stenosis, without occlusion, and recent (within two weeks) TIA or stroke, had the most benefit from surgery, assuming they were well enough for surgery, and their surgeons had a record of low complication rates (less than 7% risk of stroke and death). Carotid endarterectomy also benefited participants with 50% to 99% carotid stenosis and symptoms. For participants whose carotid artery was nearly occluded, benefit was uncertain in the long term. Surgery tended to harm participants with less than 30% stenosis. The second European Carotid Surgery Trial, which is currently recruiting participants, is exploring whether a lipid lowering agent (statin) might be a better choice than carotid endarterectomy to prevent ischaemic stroke in ipsilateral carotid stenosis, which may benefit those who did not benefit from surgery in these trials. We found the evidence to be high quality for near occlusion and less than 30% carotid stenosis; and moderate quality for 50% to 99% carotid stenosis for any stroke or operative death, as well as ipsilateral ischaemic stroke and any operative stroke or death outcome.