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Carotid Artery Stenosis – Current Evidence and Treatment Recommendations

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Carotid Artery Stenosis – Current Evidence and Treatment Recommendations Reviews/Mini-Reviews Clinical & Translational Neuroscience January-June 2021: 1–8 ª The Author(s) 2021 Carotid artery stenosis – Current Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/2514183X211001654 evidence and treatment recommendations journals.sagepub.com/home/ctn Mandy D Mu¨ller1,2 and Leo H Bonati1,3 Abstract Background: Carotid artery stenosis is an important cause for stroke. Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic carotid stenosis and to some extent in patients with asymptomatic carotid stenosis. More than 20 years ago, carotid artery stenting (CAS) emerged as an endovascular treatment alternative to CEA. Objective and Methods: This review summarises the available evidence from randomised clinical trials in patients with symptomatic as well as in patients with asymptomatic carotid stenosis. Results: CAS is associated with a higher risk of death or any stroke between randomisation and 30 days after treatment than CEA (odds ratio (OR) ¼ 1.74, 95% CI 1.3 to 2.33, p < 0.0001). In a pre-defined subgroup analysis, the OR for stroke or death within 30 days after treatment was 1.11 (95% CI 0.74 to 1.64) in patients <70 years old and 2.23 (95% CI 1.61 to 3.08) in patients 70 years old, resulting in a significant interaction between patient age and treatment modality (interaction p ¼ 0.007). The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up also favoured CEA (OR ¼ 1.51, 95% CI 1.24 to 1.85, p < 0.0001). In asymptomatic patients, there is a non-significant increase in death or stroke occurring within 30 days of treatment with CAS compared to CEA (OR ¼ 1.72, 95% CI 1.00 to 2.97, p ¼ 0.05). The risk of peri-procedural death or stroke or ipsilateral stroke during follow-up did not differ significantly between treatments (OR ¼ 1.27, 95% CI 0.87 to 1.84, p ¼ 0.22). Discussion and Conclusion: In symptomatic patients, randomised evidence has consistently shown CAS to be associated with a higher risk of stroke or death within 30 days of treatment than CEA. This extra risk is mostly attributed to an increase in strokes occurring on the day of the procedure in patients 70 years. In asymptomatic patients, there may be a small increase in the risk of stroke or death within 30 days of treatment with CAS compared to CEA, but the currently available evidence is insufficient and further data from ongoing randomised trials are needed. Keywords Carotid stenosis, carotid artery stenting, carotid endarterectomy Introduction Controversy remains over which patients require surgi- cal or endovascular therapy and which patients can be Carotid artery stenosis is an important cause for stroke. safely treated with optimal medical management alone. Carotid disease becomes more prevalent with increasing age, affecting approximately 7.5% of all men and 5.0% of all women over 80 years of age.1 The primary mechan- ism underlying cerebral ischaemia caused by carotid dis- 1 Department of Neurology and Stroke Center, University Hospital Basel, ease is plaque rupture and subsequent embolism to the University of Basel, Basel, Switzerland 2 Department of Neurosurgery, Inselspital, Bern University Hospital, brain. This has fostered the concept of the vulnerable or University of Bern, Bern, Switzerland high-risk plaque, which is prone to rupture and cause cere- 3 Department of Brain Repair and Rehabilitation, Stroke Research Centre, 2 bral ischaemia. Carotid endarterectomy (CEA) reduces the UCL Institute of Neurology, University College London, London, UK risk for cerebral ischaemia in patients with symptomatic carotid stenosis and to some extent also in patients with Corresponding author: 3,4 Leo H Bonati, Department of Neurology and Stroke Center, Department asymptomatic carotid stenosis. More than 20 years ago, of Clinical Research, University Hospital Basel, Petersgraben 4, CH-4031 carotid artery stenting (CAS) has emerged as a less inva- Basel, Switzerland. sive, endovascular treatment alternative to CEA. Email: [email protected] Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 2 Clinical & Translational Neuroscience This review summarises the available evidence from ran- 1980s and early 1990s, two large multicentre RCTs inves- domised clinical trials in patients with symptomatic carotid tigating the benefit of CEA versus medical therapy alone to stenosis as well as in patients with asymptomatic carotid prevent ipsilateral stroke in patients with symptomatic car- stenosis. otid stenosis were conducted: the North American Sympto- matic Carotid Endarterectomy Trial (NASCET) and the Risk factors for cerebral ischaemia caused European Carotid Surgery Trial (ECST). ECST showed a reduction in ipsilateral stroke with symptoms lasting longer by carotid stenosis than 7 days (including perioperative events) in the surgi- The risk for cerebrovascular events caused by carotid ste- cally treated participants from 20.6% to 6.8% at 3-year nosis is determined by several factors. Overall, the risk for follow-up (p < 0.0001).6 In NASCET, the risk of any ipsi- stroke in patients who recently experienced symptoms lateral stroke (again including perioperative events) was resulting from carotid stenosis (symptomatic carotid steno- reduced from 26% to 9% after 2 years among participants sis) is higher than in patients who have never experienced with severe stenosis (70% or greater narrowing; p < 0.001) symptoms due to carotid stenosis (asymptomatic carotid and from 22.2% to 15.7% after 5 years among stenosis). The risk for stroke is time dependent, being high- participants with moderate stenosis (50–69% narrowing; est in the first weeks after the presenting event.5 The type of p ¼ 0.045).16,17 presenting event is also of importance. The risk for recur- In both trials, the benefit of CEA was greatest in patients rence is greater in patients who experienced a hemispheric with severe carotid stenosis (>70%). In patients with mod- stroke than in patients who presented with a transient erate stenosis, the benefit of surgery was marginal and it ischaemic attack (TIA) or patients who suffered an ocular remained unclear whether all patients benefitted from event (amaurosis fugax or retinal ischaemia).5 Besides the CEA.5 presenting event and time since first symptoms, the degree In the beginning of the 21st century, CAS was intro- of ipsilateral carotid stenosis is another important risk fac- duced as a less invasive treatment alternative for carotid tor to determine future stroke risk.5,6 Stroke risk is highest stenosis. Initially, percutaneous transluminal balloon in patients with severe carotid stenosis.7 Other known risk angioplasty without the insertion of stent devices was per- factors for future stroke include increasing age, an irregular formed. Later, stent devices were specifically developed and ulcerated plaque surface morphology (which is patho- for the carotid arteries and primary stenting has since logically unstable), absence of angiographic collateral replaced balloon angioplasty alone as the endovascular flow, impaired cerebral reactivity, high frequency of tran- treatment of choice.18 scranial Doppler-detected emboli to the brain, hypertension Today, various stent devices with different designs and and coronary heart disease.5,7,8 configurations are in use. Previous studies demonstrated a More recent research has focussed on the use of differ- higher risk of stroke during and/or immediately after the ent imaging modalities to identify vulnerable or high-risk procedure in patients treated with open-cell stents due to plaques and thus patients at particularly high risk for future incomplete coverage of the atherosclerotic lesion because stroke. MRI is able to visualise structural correlates of pla- of larger open areas between struts compared with closed- que instability with good histopathological correlation.9,10 cell stents.19–21 Closed-cell devices on the other hand are Intra-plaque haemorrhage (IPH) constitutes one of the most more rigid and therefore less flexible.22 Consequently, promising markers for plaque instability. Plaques with mesh covered stents have been developed to combine the signs of IPH have a fundamentally altered biology, exhibit- lower risk of peri-procedural stroke associated with closed- ing rapid progression despite statin therapy and increasing cell stents and the flexibility of open-cell stents.23 the risk of cerebral ischaemia compared to plaques without Potential advantages of CAS compared to CEA include IPH.11–13 IPH is more prevalent in patients with sympto- the avoidance of a surgical incision in the neck and thus a matic carotid stenosis and occurs in about 30–50%, while it lower risk of local complications such as cranial or cuta- is found in about 20–30% of patients with asymptomatic neous nerve injury and reduction in the rate of general carotid stenosis.14 A recent meta-analysis of individual surgical complications such as myocardial infarction.24 patient data showed an increased risk of ipsilateral stroke However, CAS does not remove the atherosclerotic lesion in patients with IPH even when carotid stenosis was mild
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