Recently, the New England Journal of Medicine published two consecutive multicenter RCTs on the two main surgical treatments for carotid stenosis – CEA for intracarotid plaque resection and CAS for carotid stenting – with 5-year follow-up of ACT-1 and 10-year follow-up of CREST, respectively. What are the new implications of the publication of the new results for surgical intervention strategies for asymptomatic carotid stenosis, which has been controversial for many years? Let us now compile what new information these two papers bring to light.
I. What are the ACT-1 and CREST trials?
Asymptomatic Carotid Trial (ACT)
A prospective multicenter randomized controlled study. Compared the efficacy of CAS and CEA with a cerebral protection device in patients with asymptomatic severe carotid stenosis. A total of 1453 patients were enrolled and followed up for 5 years. Main follow-up indicators: stroke, infarction and death 30 days after surgery; ipsilateral stroke within 1 year after surgery; stroke and death 5 years after surgery.
Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)
A prospective multicenter global 117-center, randomized controlled study. Compared the outcomes of patients with severe carotid stenosis including symptomatic and asymptomatic, receiving CAS and CEA. A total of 1453 patients were included and followed for 10 years. Main follow-up indicators: death, stroke and infarction at 30 days after surgery; ipsilateral stroke at 5 years after surgery; and ipsilateral stroke at 10 years after surgery.
II. What are the main results of the latest ACT-1 and CREST trials?
ACT-1 main results
In a nutshell, CAS is no less effective than CEA in the medium to long term for asymptomatic severe carotid stenosis.
1. General patient data: age <80 years mean 67.8 years, with >70% mean 73%, severe carotid stenosis confirmed by ultrasound or angiography, no high risk of surgical complications, no clinical symptoms directly related to carotid stenosis.
2, Primary endpoint 30 days postoperative stroke, infarction or death, 1 year postoperative ipsilateral stroke, occurrence of.
CAS was not inferior to CEA 3.8% vs. 3.4%, P=0.011,.
3. Other indicators
30 days postoperatively.
The incidence of ipsilateral mini-stroke CAS was higher than that of CEA, but not statistically different. The composite incidence of cranial nerve injury, peripheral nerve injury, non-cerebrovascular hemorrhage, endarterectomy, or puncture site hematoma was lower for CAS than for CEA, but not statistically different. See the following table, the
1 year postoperatively.
Composite endpoint of death, stroke, and infarction: no significant difference between CAS and CEA groups 3.8% vs. 3.4%,.
5 years postoperatively.
Ipsilateral stroke incidence: no significant difference between CAS and CEA groups 0.5%/year vs. 0.4%/year.
CREST main results combined with the results reported in 2010.
In a nutshell, there was no significant difference between CAS and CEA in the 10-year follow-up results, and subgroup analysis of both symptomatic and asymptomatic patients yielded the same results.
1. 30 days postoperatively.
The incidence of stroke was significantly higher in CAS than in CEA4.1% vs. 2.3%, P=0.01, and the incidence of heart attack was significantly lower in CAS than in CEA1.1% vs. 2.3%, P=0.03, with no difference in mortality. See the following table.
2. 5 years after surgery.
No significant difference between CAS and CEA for ipsilateral stroke 0.7%/year vs. 0.6%/year,.
3, 10 years postoperatively.
No significant difference between CAS and CEA, 11.8% vs. 9.9%, for the primary composite focus on incidence of stroke, infarction, or death.
Further subgroup analysis showed no significant difference in the incidence of the primary composite endpoint event stroke, heart attack or death, on CAS versus CEA in the symptomatic and asymptomatic carotid artery stenosis patient groups.
Third, for patients with asymptomatic carotid stenosis, should surgical intervention be performed?
The two major studies, ACT-1 and CREST, only provide us with a clinical basis for CEA and CAS selection during surgical intervention in asymptomatic carotid stenosis. However, it remains unknown whether such patients must all receive aggressive surgical intervention. Two other trials, the ACASAsymptomatic Carotid Atherosclerosis Study, and the ACSTAsymptomatic Carotid Surgery Trial, have to be mentioned here.
ACAS was the earliest RCT of CEA vs. CEA for asymptomatic carotid stenosis, and ACST was the largest sample size RCT of CEA vs. CEA for asymptomatic carotid stenosis.
The results of both studies were very interesting: the first impression was that CEA did reduce the risk of stroke compared with BMT. See the table below.
However, since the risk of stroke is already very low with BMT alone, that is, for every 1000 asymptomatic patients treated with CEA, only about 50 actually receive stroke prevention benefit, the vast majority of patients will not have a stroke with BMT intervention alone. See the table below.
Therefore, the term “highly selected” patients appears frequently in the description of the conditions in which surgical intervention is recommended for asymptomatic patients with carotid stenosis in guidelines from North America, Oceania, the United Kingdom, Europe, and other countries and regions. For “highly selected” patients, aggressive surgical intervention is recommended.
Fourth, how to screen “highly selected” patients?
In the author’s opinion, “highly selected” patients are those who have a high risk index, are prone to future progression and have a poor prognosis in stroke, and should be evaluated preoperatively and have strict surgical indications to be “highly selected”. “The following points should be met A high risk of stroke may be associated with the following
severe stenosis
progressive stenosis
hypoechoic plaques
Irregular plaque
Plaque computer classification
1.In Geroulakos type 1/type 2 plaques, the increased risk of stroke is shown in the following table.
2. For larger plaque area and Juxta-luminal Black Area, the increased risk of stroke is shown in the table below.
ACSRS risk prediction algorithm
Naylor et al. developed a correlation scale between GSM, plaque area and stroke risk.
Intra-plaque hemorrhage
TCD suggests embolism
CT/MRI shows asymptomatic infarction
At this point, you may think that patients with the above points are “highly selected” patients, right? But Ann Intern MedIF=17.81, the latest literature report “slapped” again. They say “there is no accurate empirical or reliable risk stratification tool to distinguish between surgical interventions and stroke risk in patients with BMT”.
V. Summary and outlook
1. For asymptomatic carotid stenosis, BMT is indicated in almost all patients. The “OIIP” principle of “Optimization, Intensification, Individualization, Precision,” should be followed. The “OIIP” principle should be followed.
2, need to strictly select patients for surgical intervention.
3, CEA is the gold standard, but the status of CAS is gradually increasing, and the latest research results suggest that it is comparable to CEA.
4, optimize the measures of surgical interventions to reduce all kinds of complications. We need to follow the “4S+1A+1D principle” that is “Simple, Simple, Safe, Short, Save, Avoidance & Durable”.
5, look forward to new research to give answers – SPACE2 /CREST2
Conclusion
These two recent reports in the New England Journal of Medicine have further elevated the status of CAS and have somewhat shaken the traditional “gold standard” position of CEA. However, further research is needed to confirm the choice of surgical intervention versus pharmacological treatment for patients with asymptomatic carotid stenosis.
”If winter comes, can spring be far behind?”, I believe that with the publication of the results of SPACE2 and CREST2 studies, there may be more results that will change or even overturn the existing clinical thinking. While we wait and see, we also need to fully explore and integrate the superior patient and medical resources in China, cooperate and win-win, design clinical studies, and produce our Chinese data.
The 5th Chinese Carotid Surgery Summit and International Carotid Surgery Summit CCS 2016 will be held in Shanghai on 22-24.04.2016. We hope that all colleagues will come and discuss the development of carotid surgery in China at that time.