CURRICULUM IN CARDIOLOGY - JOURNAL REVIEW

Year : 2016  |  Volume : 2  |  Issue : 1  |  Page : 41-42

Stent versus Surgery for Asymptomatic Carotid Stenosis

Preetam Krishnamurthy
Department of Cardiology, AIIMS, New Delhi, India

Correspondence Address:
Preetam Krishnamurthy
Department of Cardiology, AIIMS, New Delhi
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2395-5414.182987

Article

Introduction

• Stroke is the 5^th leading cause of death in US; 3^rd leading cause in India ^[1]
• Extracranial carotid artery stenosis – cause for 20% of stroke
• Asymptomatic carotid atherosclerosis study trial and asymptomatic carotid surgery trial showed benefit in early intervention in patients with asymptomatic carotid artery stenosis > 60%^[2],[3]
• The use of carotid artery stenting (CAS) was shown to be noninferior to carotid endartrectomy (CEA) in patients with significant carotid artery stenosis (carotid revascularization endarterectomy versus stenting trial [CREST]) but was not adequately powered to show noninferiority in the asymptomatic patient sub group.^[4]

Methods

• The trial was a prospective multicenter randomized control trial, enrolled patients from March 2005 to January 2013. The events were independently monitored by separate committees
• The study protocol was similar to the CREST trial but only asymptomatic patients were enrolled
• Asymptomatic (no symptoms of TIA/stroke/amaurosisfugax in the past 180 days) carotid artery stenosis (>70% by ultrasound/angiography) patients (n = 1481) were enrolled in the trial and randomized in the ratio 3:1 between CAS group and CEA group
• Patients with confounding factors that could affect assessment at the time of follow-up were excluded (e.g., dementia, neurological illness)
• CAS group patients received aspirin 325 mg twice daily 48 h before procedure and indefinitely afterward. Clopidogrel was administered 48 h before procedure and continued for 1 month postprocedure. Closed cell, nitinol, tapering stents were used with distal embolic protection device
• CEA group received 325 mg aspirin before procedure and continued indefinitely after the procedure
• Patients were followed up for 5 years postprocedure.

• Primary endpoint of the study was composite of death, stroke (ipsilateral or contralateral), major or minor or myocardial infarction during the 30 days after the procedure or ipsilateral stroke during the 365 days after the procedure
• Kaplan–Meir analysis was used to estimate the end point event rates to test the noninferiority hypothesis
• • The study design required 1681 patients with 80% power to detect noninferiority margin at P = 0.05. Due to slow enrollment, only 1453 patients were included in the trial corresponding to a power of 75% for the same design.

Results

• The attrition rates were similar in both groups
• Primary end point (event rate) estimated in the CAS group was 3.8 ± 0.59% compared to 3.4 ± 0.98% (CEA group). The upper limit of the one-sided confidence interval between the two groups was 2.27% (less than the prespecified limit 3%)
• Secondary end points
• • Composite outcome of death, myocardial infarction, stroke was higher in CAS group (3.3% vs. 2.6%) but was not significant (P = 0.60)
  • Death/stroke event rates was 2.9% in CAS group versus 2.7% in CEA group but was not statistically significant (P = 0.33).
  
  
  
• The rate of stroke in stenting group was 2.8% versus 1.4% in CEA group though the difference was not statistically different
• Cranial nerve injury was more common in the CEA group (0.1% vs. 1.1%; P = 0.02).

Discussion

• Multiple studies have shown benefit of intervening in asymptomatic patients with significant carotid artery stenosis.^[2],[3],[5] These studies were done in early 90's before the current standard of optimized medical therapy was accepted
• Trials that have compared stenting and CEA in symptomatic patients have shown conflicting results. There are no exclusive trials comparing CEA versus CAS in asymptomatic patients ^[6]
• This trial has shown that CAS is noninferior to CEA in patients with carotid artery stenosis. There was increased incidence of stroke in patients who underwent CAS though not statistically significant
• The period of enrollment of trial was prolonged (March 2005–January 2013) and there were lower than expected patients on follow-up reducing the power of the study
• There is a lack of characterization of patients who were screened but not enrolled in the trial
• Recent observation studies suggest patients managed on best medical treatment had < 1% annual risk of stroke in patients with asymptomatic carotid artery stenosis (in comparison to risk of 2–3% annual risk in studies published in 80's and 90's).^[7],[8] This fall in risk should likely translate into a further fall in the absolute benefit in revascularization
• Medical therapy arm was not included in the trial. The potential benefit of CAS over medical therapy is unknown. CREST 2 trial might help to understand the benefit of revascularization, if any, over medical therapy
• Risk stratification of patients with asymptomatic carotid artery stenosis would be more helpful to identify patients who may benefit from revascularization. Some method that are being tried include detecting microemboli in transcranial Doppler, identification of unstable carotid plaque in ultrasound, identification of intraplaquehaemorrhages in magnetic resonance imaging (MRI), silent embolic infarct in computed tomography or MRI, and progression in severity of stenosis could potentially predict the risk of future stoke and benefit from revasculatisation.^[9]

Conclusion

• ACT 1 trial showed that in patients with asymptomatic CAS who were not at high risk for surgical complications, CAS was noninferior to CEA. The potential benefit over medical therapy is still inconclusive and identification of high risk groups who would benefit more from revascularization leave a lot of scope for future trials.

References

1.	World Health Organization. World Health Statistics 2012. Available from: @http://www.who.int/gho/publications/world_health_statistics/ 2012/en/. [Last accessed on 2016 Apr 23].
2.	Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273:1421-8.   [PUBMED]
3.	Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): A multicentre randomised trial. Lancet 2010;376:1074-84.   [PUBMED]
4.	Brott TG, Hobson RW 2nd, Howard G, Roubin GS, Clark WM, Brooks W, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363:11-23.   [PUBMED]
5.	Hobson RW 2nd, Weiss DG, Fields WS, Goldstone J, Moore WS, Towne JB, et al. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group. N Engl J Med 1993;328:221-7.
6.	Rosenfield K, Matsumura JS, Chaturvedi S, Riles T, Ansel GM, Metzger DC, et al. Randomized trial of stent versus surgery for asymptomatic carotid stenosis. N Engl J Med 2016;374:1011-20.
7.	Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: A prospective, population-based study. Stroke 2010;41:e11-7.
8.	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;40:e573-83.
9.	Paraskevas KI, Spence JD, Veith FJ, Nicolaides AN. Identifying which patients with asymptomatic carotid stenosis could benefit from intervention. Stroke 2014;45:3720-4.