13th May 2025, A/Prof Chee L Khoo
Patients with carotid stenosis either go for intensive medical treatment or carotid endarterectomy. Trials conducted in the 1980s and 1990s have shown that carotid endarterectomy (CEA) can reduced the risk of stroke in patients with symptomatic carotid stenosis of ≥ 50% and to a smaller extent in patients with asymptomatic stenosis, compared with best medical treatment. Best medical treatment were very basic then. We have previewed the intensive lipid lowering therapy for ASCVD prevention multiple times. Do we need to re-look at the choice between CEA and best medical treatment for carotid stenosis management?
Symptomatic patients
In the landmark trial, MRC European Carotid Surgery Trial (ECST) back in 1998, 3024 patients who had a recent (< 6 months) ischaemic stroke (CVA or TIA) and any degree of carotid stenosis were randomised to either “CEA as soon as possible” with “avoid surgery if at all possible, for as long as possible” (1). Both groups were on anti-platelet and lipid lowering therapies. The risk of major stroke increased with the degree of stenosis without surgery. CEA on the other hand, decreased the risk of major stroke from 26.5% to 14.9% over a three-year period.
The other landmark trial was the North American Symptomatic Carotid Endarterectomy Trial (NASCET) also published in 1998 (2). 2267 patients with stenosis of < 70 % were randomly assigned to either surgery or medical treatment and follow up over 5 years. The five-year failure rate for patients with 50-69 % stenosis was 22.2 % for medically treated patients and 15.7% for surgically treated patients. There was a net increase in risk at 30 days associated with surgery of 4.3 percent for any stroke or death for surgically treated patients.
Rothwell et al pooled the data from both trials and concluded that surgery was 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 (3).
In a Cochrane Review by Rerkasem et al on surgery in symptomatic patients with carotid stenosis in 2020, CEA reduced the risk of further stroke for people with significant stenosis (4). Results were particularly striking for older people, male participants, those with a significant stenosis (70% to 99%), and those who were operated on within two weeks of their TIA or stroke. Endarterectomy might be of some benefit for participants with 50% to 69% stenosis. They did not find any benefit of carotid surgery for those in whom the stenosis was minor (less than 50%) or where the carotid artery was almost blocked (near occlusion).
Asymptomatic patients
In the Asymptomatic Carotid Atherosclerosis Study (ACAS) (1995), for asymptomatic patients with carotid artery stenosis of ≥ 60% and with good general health, elective surgery was compared with medical treatment (5). The risk of ipsilateral stroke was 5.1% compared with 11.0% in the medical treatment. Perioperative morbidity and mortality were worse in the first month postoperatively and was < 3% overall which include 1.2% of patients who experienced a stroke following preoperative arteriography.
In the Asymptomatic Carotid Surgery Trial (ACST-1) (2010), 3120 asymptomatic patients with stenosis ≥60% were randomised to either immediate surgery or indefinite deferral and followed up for 10 years (6). The immediate surgery group had a 46% reduction in ipsilateral stroke incidence compared with the deferred group. Perioperative risk of stroke or death within 30 days was 3·0%. Of note, while antihypertensive therapy and anti-platelet therapy was common in both groups, only 10% of patients at baseline (1993) were on lipid lowering therapy.
Anne Abbott conducted a systematic review of medical intervention alone found that in asymptomatic carotid stenosis patients that rates of ipsilateral and any-territory stroke (+/−TIA), with medical intervention alone, have fallen significantly since the mid-1980s (7). Not only does current vascular disease medical intervention alone is now best for stroke prevention, there are other cardiovascular benefits.
The Australian and New Zealand Living Clinical Guidelines for Stroke Management have the following recommendations for symptomatic carotid stenosis:
Strong Recommendation (Carotid surgery)
- Carotid endarterectomy is recommended for patients with recent (<3 months) non-disabling carotid artery territory ischaemic stroke or TIA with ipsilateral carotid stenosis measured at 70-99% (NASCET criteria if it can be performed by a specialist team with audited practice and a low rate (<6%) of perioperative stroke and death.
- Carotid endarterectomy can be considered in selected patients with recent (<3 months) non-disabling ischaemic stroke or TIA patients with symptomatic carotid stenosis of 50–69% (NASCET criteria) if it can be performed by a specialist team with audited practice and a very low rate (<3%) of perioperative stroke and death.
- Carotid endarterectomy should be performed as soon as possible (ideally within two weeks) after the ischaemic stroke or TIA.
- All patients with carotid stenosis should be treated with intensive vascular secondary prevention therapy.
That was for symptomatic carotid stenosis (so-called secondary prevention) but I had great difficulty locating guidelines for asymptomatic carotid stenosis. This was from Safer Care Victoria:
- Medical therapy alone is recommended for most patients with asymptomatic carotid artery stenosis and has been associated with low annual stroke rates of less than 1 per cent.
- In selected asymptomatic patients, carotid endarterectomy surgery may be indicated for patients who have carotid artery stenosis of greater than 70 per cent.
The recommendations appear to be primarily based on Abbott et al systematic review above.
The latest very ingenious trial appears to throw all the recommendations in the air. In the Second European Carotid Surgery Trial (ECST-2), Donners A et al. recently published a 2-year interim data on a multicentre randomised trial which aimed to assess whether patients with symptomatic and asymptomatic carotid stenosis with a low or intermediate predicted risk of stroke, who received optimised medical therapy (OMT), would benefit from additional revascularisation (10). 429 patients were randomly assigned to OMT alone or OMT plus revascularisation. They included carotid stenosis in both symptomatic and asymptomatic patients. To be eligible, symptomatic patients need to have a 5 year stroke risk of >20% and asymptomatic patients need to be asymptomatic for at least 180 days and have 5 year stroke risk of >5% according to the Carotid Artery Risk (CAR) score.
The total cholesterol and LDL-C targets were <4.0mmol/L and <2.0 mmol/L respectively. BP targets were 140/90 mmHg (135/85 at home) if <80 years and 150/90mmHg (145/95 at home). If revascularisation was to be performed, it was to be done within 2 weeks of randomisation if symptomatic and < 4 weeks if asymptomatic.
The primary outcomes which were hierarchically assessed were periprocedural death, fatal stroke, or fatal myocardial infarction, non-fatal stroke, non-fatal myocardial infarction as well as any new silent cerebral infarction on MRI (or CT) within 2 years of follow-up.
The primary analysis was performed based on a hierarchical outcome analysed using the Finkelstein–Schoenfeld method and win ratio. Essentially, each patient in the OMT group was compared as a pair with each patient in the OMT plus revascularisation group, with a win declared for the patient with a better outcome within the pair considering the time to event if both patients within a pair had the same event (a tie was declared if neither patient in the pair had a better outcome).
There were no differences in outcomes whether patients were in the OMT alone or OMT with revascularisation. Based on 5228 (11·4%) wins for the OMT alone group, 5173 (11·3%) wins for the OMT plus revascularisation group, and 35 395 (77·3%) ties between the groups, the win ratio for the primary outcome was 1·01 (95% CI 0·60–1·70; p=0·97). The numbers of patients with new cerebral infarction on imaging at 2-year follow-up were similar between treatment groups.
Thus far, the benefits of surgery for carotid stenosis > 50% over OMT is becoming less convincing whether in symptomatic or asymptomatic patients. There are other factors to consider apart from symptoms and the degree of stenosis.
Patients with stenosis and one or more of these high risk features (HRF): plaque echolucency, large lipid rich necrotic core, thin/ruptured fibrous cap; plaque ulceration; intraplaque haemorrhage, MRI diagnosed lipid or necrotic core surrounded by fibrous tissue with possible calcification, MRI diagnosed complex plaque with surface defect, haemorrhage, or thrombus, spontaneous micro-embolism during > 1 hour of transcranial Doppler monitoring (8,9).
ACST-1 and ACAS reported that increasing stenosis severity was not associated with higher rates of stroke in BMT patients but it is an important predictor for late ipsilateral stroke/TIA, but only with concurrent HRFs (8).
Another group that may warrant consideration of surgical intervention may be carotid stenosis in symptomatic patients who are having recurrent strokes irrespective of the degree of stenosis.
What does the new data mean in primary care?
Should we be screening for carotid artery stenosis? The prevalence of >50% and >70% ACS in 23706 people recruited from four general population-based cohorts was 2% and 0.5%, respectively (10). The yield for finding > 70% atherosclerotic carotid stenosis through unselected screening of patients aged < 80 years would be < 2%, which is neither cost nor clinically effective. I always feel guilty that perhaps, I should have done a carotid duplex before the patient got admitted to hospital with an ischaemic stroke. International guidelines have not recommended screening for carotid artery stenosis. I sometimes arrange for a carotid duplex looking for evidence of any atherosclerosis, obstructive or not.
What the latest data remind us that optimised medical therapy is paramount in preventing strokes in patients with carotid stenosis. Just like what we need to do for patients with coronary artery disease. Once again, it’s not a matter of the degree of stenosis. Any stenosis is atherosclerosis and aggressive lipid lowering is warranted.
References:
- Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998 May 9;351(9113):1379-87. PMID: 9593407.
- Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998 Nov 12;339(20):1415-25.
- Rothwell PM, Eliasziw M, Gutnikov SA, et al. Carotid Endarterectomy Trialists’ Collaboration. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet. 2003 Jan 11;361(9352):107-16.
- Rerkasem A, Orrapin S, Howard DP, Rerkasem K. Carotid endarterectomy for symptomatic carotid stenosis. Cochrane Database Syst Rev. 2020 Sep 12;9(9):CD001081.
- Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995 May 10;273(18):1421-8.
- Halliday A, Harrison M, Hayter E, et al. Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet. 2010 Sep 25;376(9746):1074-84.
- Abbott AL. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis. Stroke. 2009 Oct;40(10):e573-83.
- Kamtchum-Tatuene J, Noubiap JJ, Wilman AH, Saqqur A, Jickling GC. Prevalence of high-risk plaques and risk of stroke in patients with asymptomatic carotid stenosis: a meta-analysis. JAMA Neurol 2020;77:1e12.
- Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL,Yuan C. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 2002;106:1368e73.
De Weerd M, Greving JP, Hedblad B, Lorenz MW, Mathiesen EB, O’Leary DH. Prevalence of asymptomatic carotid artery stenosis in the general population: An individual participant data metaanalysis. Stroke 2010;41:1294e7.