Is surveillance for restenosis justified after carotid revascularisation?
Authors: Seemant Chaturvedi
Journal: The Lancet Neurology (2018)

A common dilemma in clinical practice is whether to request an imaging test if the prognostic implications of the results of the test are uncertain. An example of such a dilemma is whether surveillance for recurrent stenosis should be routine in patients who have undergone carotid endarterectomy or stenting either after an ischaemic stroke or as a preventive procedure. Surveillance for restenosis after a carotid revascularisation procedure is common practice in many centres. Carotid ultrasound is usually done within the first 6 months after the procedure, and then at yearly intervals, to check for restenosis. In addition to detecting restenosis, surveillance can also provide information on patency of the contralateral internal carotid artery. In an analysis of 4127 asymptomatic elderly patients who underwent carotid ultrasound,1Keyhani S Cheng EM Naseri A et al.Common reasons that asymptomatic patients who are 65 years and older receive carotid imaging.JAMA Intern Med. 2016; 176: 626-633Crossref PubMed Scopus (16) Google Scholar the second most frequent reason for follow-up imaging was previously reported carotid stenosis, with presence of a bruit being the most common indication. In The Lancet Neurology, Leo H Bonati and colleagues present data from the International Carotid Stenting Study (ICSS), in which participants with symptomatic carotid stenosis were randomly allocated either stenting or endartectomy.2Bonati LH Gregson J Dobson J et al.Restenosis and risk of stroke after stenting or endarterectomy for symptomatic carotid stenosis in the International Carotid Stenting Study (ICSS): secondary analysis of a randomised trial.Lancet Neurol. 2018; (published online May 31.)http://dx.doi.org/10.1016/S1474-4422(18)30195-9Summary Full Text Full Text PDF PubMed Scopus (74) Google Scholar Of 1713 patients enrolled, 1530 were followed up with carotid ultrasound for a median of 4·0 years (IQR 2·3–5·0). The cumulative 5-year risk of moderate or higher (≥50%) restenosis was 40·7% with stenting and 29·6% with endarterectomy (unadjusted hazard ratio [HR] 1·43, 95% CI 1·21–1·72; p<0·0001). In patients with moderate or higher (≥50%) stenosis, the cumulative risk of ipsilateral stroke at 6 years was increased in the overall study population (unadjusted HR 3·18, 95% CI 1·52–6·67; p=0·002) and in those who underwent endarterectomy (5·75, 1·80–18·33; p=0·003). In patients with severe (≥70%) stenosis, risk for restenosis did not differ between treatment groups (cumulative 5-year risk 10·6% with stenting vs 8·5% with endarterectomy; unadjusted HR 1·20, 95% CI 0·86–1·69; p=0·27) and no increased risk of ipsilateral stroke was noted (1·79, 0·64–4·99; p=0·263). Definitions of restenosis are worth considering, particularly when comparing these results with those of other trials. The ICSS investigators used a cutoff for peak systolic velocity of greater than 1·3 m/s to define moderate or higher (≥50%) stenosis and a cutoff of greater than 2·1 m/s to define severe (≥70%) stenosis. By contrast, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) used a higher threshold (>3·0 m/s) to define severe (≥70%) stenosis.3Lal BK Beach KW Roubin GS et al.Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomized controlled trial.Lancet Neurol. 2012; 11: 755-763Summary Full Text Full Text PDF PubMed Scopus (295) Google Scholar Some imaging specialists recommend the higher threshold in stented vessels because the presence of a stent alters the elasticity of the vessel wall.4Lal BK Hobson RW Tofighi B Kapadia I Cuadra S Jamil Z Duplex ultrasound velocity criteria for the stented carotid artery.J Vasc Surg. 2008; 47: 63-73Summary Full Text Full Text PDF PubMed Scopus (134) Google Scholar Data from ICSS suggest that the value of information obtained from routine surveillance after endarterectomy or stenting is uncertain for guiding a change in treatment. Although an increased risk of stroke was seen in patients with at least moderate (≥50%) stenosis, the mechanism of the stroke was not clear, and this information could be important because if a stroke is due to cardiac embolism or is a lacunar stroke, then operating on the restenotic lesion will not be helpful and could be harmful. Patients with restenosis might have a greater likelihood of resistant atherosclerosis compared with those without restenosis, which could be associated with a higher likelihood of intracranial stenosis or small-vessel pathology. Future studies should attempt to understand the mechanism of ipsilateral stroke in patients with restenosis. In a previous study of 1820 patients with severe carotid stenosis, cardioembolic events and small-vessel disease were thought to account for close to half of subsequent strokes.5Inzitari D Eliasziw M Gates P et al.The causes and risk of stroke in patients with asymptomatic internal-carotid artery stenosis.N Engl J Med. 2000; 342: 1693-1700Crossref PubMed Scopus (581) Google Scholar The practical conclusions that clinicians should take from this study are also unclear. If a patient has moderate or higher (≥50%) restenosis, should medical treatment be intensified? Should more stringent blood pressure or lipid targets be used? Should reintervention be considered, in the form of new stenting or endarterectomy? Intensified medical treatment seems reasonable, but its efficacy has not been proven in clinical trials of patients with a previous stroke. Endarterectomy or stenting procedures for asymptomatic stenosis in the general population are of uncertain value, so undertaking another procedure for asymptomatic restenosis is even less persuasive because the risk for complications from operating on a restenotic lesion is high so the risk:benefit ratio is less favourable for a patient with asymptomatic restenosis.6Chaturvedi S Chimowitz M Brown RD Lal BK Meschia JF The urgent need for contemporary clinical trials in patients with asymptomatic carotid stenosis.Neurology. 2016; 87: 1-8Crossref Scopus (14) Google Scholar Moreover, reintervention would typically be considered if stenosis progresses beyond 70% but, in the current study, those patients did not have an increased stroke risk, although the power to detect such a difference was limited in ICSS. Along with defining the mechanism of stroke associated with restenosis, future analyses should also address the pathology of these lesions. Previous published work has identified myointimal hyperplasia with early recurrent stenosis and so-called typical atherosclerotic changes in patients with late restenosis (ie, >1 year from the index procedure). Female sex, diabetes, dyslipidaemia, continued smoking, and impaired cerebrovascular reactivity have been associated with restenosis.3Lal BK Beach KW Roubin GS et al.Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomized controlled trial.Lancet Neurol. 2012; 11: 755-763Summary Full Text Full Text PDF PubMed Scopus (295) Google Scholar, 7Zapata-Arriaza E Moniche F Gonzalez A et al.Predictors of restenosis following carotid angioplasty and stenting.Stroke. 2016; 47: 2144-2147Crossref PubMed Scopus (28) Google Scholar Since predictors of restenosis exist, a targeted imaging programme focused on patients with the highest risk for restenosis might be a more sensible strategy than indiscriminate surveillance of all patients. Guidelines from the American Heart Association and the American Stroke Association state that routine long-term follow-up imaging with carotid duplex ultrasound is not warranted in patients after revascularisation.8Kernan WN Ovbiagele B Black HR et al.Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack.Stroke. 2014; 45: 2160-2236Crossref PubMed Scopus (2990) Google Scholar By identifying the group of patients at increased risk of stroke, the current work by Bonati and colleagues shows that there is some prognostic value to follow-up imaging, but the treatment steps to address the increased stroke risk are uncertain. I am a member of the Executive Committee for the CREST 2 and ACT 1 studies. Restenosis and risk of stroke after stenting or endarterectomy for symptomatic carotid stenosis in the International Carotid Stenting Study (ICSS): secondary analysis of a randomised trialAt least moderate (≥50%) restenosis occurred more frequently after stenting than after endarterectomy and increased the risk for ipsilateral stroke in the overall population. Whether the restenosis-mediated risk of stroke differs between stenting and endarterectomy requires further research. Full-Text PDF Open Access