Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial.

BACKGROUND: Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. METHODS: Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. FINDINGS: 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0-5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72-1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28-2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02-2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups. INTERPRETATION: Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. FUNDING: Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

Percutaneous transluminal balloon angioplasty and stenting for carotid artery stenosis.

BACKGROUND: Endovascular treatment by transluminal balloon angioplasty or stent insertion may be a useful alternative to carotid endarterectomy for the treatment of atherosclerotic carotid artery stenosis. This review updates a previous version first published in 1997 and subsequently updated in 2004 and 2007. OBJECTIVES: To assess the benefits and risks of endovascular treatment compared with carotid endarterectomy or medical therapy in patients with symptomatic or asymptomatic carotid stenosis. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched January 2012) and the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE (1950 to January 2011), EMBASE (1980 to January 2011) and Science Citation Index (1945 to January 2011). We also searched ongoing trials registers (January 2011) and reference lists and contacted researchers in the field. SELECTION CRITERIA: Randomised trials comparing endovascular treatment (including balloon angioplasty or stenting) with endarterectomy or medical therapy for symptomatic or asymptomatic atherosclerotic carotid stenosis. DATA COLLECTION AND ANALYSIS: One review author selected trials for inclusion, assessed trial quality and extracted data. A second review author independently validated trial selection and a third review author independently validated data extraction. We calculated treatment effects as odds ratios (OR) and 95% confidence intervals (CI), with endovascular treatment as the reference group. We quantified heterogeneity using the I(2) statistic. MAIN RESULTS: We included 16 trials involving 7572 patients. In patients with symptomatic carotid stenosis at standard surgical risk, endovascular treatment was associated with a higher risk of the following outcome measures occurring between randomisation and 30 days after treatment than endarterectomy: death or any stroke (the primary safety outcome) (OR 1.72, 95% CI 1.29 to 2.31, P = 0.0003; I(2) = 27%), death or any stroke or myocardial infarction (OR 1.44, 95% CI 1.15 to 1.80, P = 0.002; I(2) = 7%), and any stroke (OR 1.81, 95% CI 1.40 to 2.34, P < 0.00001;I(2) = 12%). The OR for the primary safety outcome was 1.16 (95% CI 0.80 to 1.67) in patients < 70 years old and 2.20 (95% CI 1.47 to 3.29) in patients ≥ 70 years old (interaction P = 0.02).The rate of death or major or disabling stroke did not differ significantly between treatments (OR 1.28, 95% CI 0.93 to 1.77, P = 0.13; I(2) = 0%). Endovascular treatment was associated with lower risks of myocardial infarction (OR 0.44, 95% CI 0.23 to 0.87, P = 0.02; I(2) = 0%), cranial nerve palsy (OR 0.08, 95% CI 0.05 to 0.14, P < 0.00001; I(2) = 0%) and access site haematomas (OR 0.37, 95% CI 0.18 to 0.77, P = 0.008; I(2) = 27%).The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up (the primary combined safety and efficacy outcome) favoured endarterectomy (OR 1.39, 95% CI 1.10 to 1.75, P = 0.005; I(2) = 0%), but the rate of ipsilateral stroke after the peri-procedural period did not differ between treatments (OR 0.93, 95% CI 0.60 to 1.45, P = 0.76; I(2) = 0%).Restenosis during follow-up was more common in patients receiving endovascular treatment than in patients assigned surgery (OR 2.41, 95% CI 1.28 to 4.53, P = 0.007; I(2) = 55%). In patients with asymptomatic carotid stenosis, treatment effects on the primary safety (OR 1.71, 95% CI 0.78 to 3.76, P = 0.18; I(2) = 0%) and combined safety and efficacy outcomes (OR 1.75, 95% CI 0.92 to 3.33, P = 0.09; I(2) = 0%) were similar to symptomatic patients, but differences between treatments were not statistically significant. Among patients not suitable for surgery, the rate of death or any stroke between randomisation and end of follow-up did not differ significantly between endovascular treatment and medical care (OR 0.22, 95% CI 0.01 to 7.92, P = 0.41; I(2)= 79%). AUTHORS' CONCLUSIONS: Endovascular treatment is associated with an increased risk of peri-procedural stroke or death compared with endarterectomy. However, this excess risk appears to be limited to older patients. The longer term efficacy of endovascular treatment and the risk of restenosis are unclear and require further follow-up of existing trials. Further trials are needed to determine the optimal treatment for asymptomatic carotid stenosis.

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

BACKGROUND: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. METHODS: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. FINDINGS: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). INTERPRETATION: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Randomized controlled trials comparing endarterectomy and endovascular treatment for carotid artery stenosis: a Cochrane systematic review.

BACKGROUND AND PURPOSE: Endovascular treatment of carotid stenosis may be an alternative to surgical endarterectomy. We conducted a systematic review of the randomized evidence to assess the benefits and risks of endovascular treatment compared to surgery. METHODS: Cochrane registers and online databases were searched and researchers in the field contacted. Outcome events were compared using odds ratios (ORs) calculated using the Peto fixed effect and Mantel-Haenszel random effects models if there was significant heterogeneity. RESULTS: Ten trials involving 3178 patients were included. Not all contributed to each analysis. The primary outcome comparison of any stroke or death within 30 days of treatment favored surgery (fixed-effects OR 1.35), the difference was not statistically significant using the random effects model. Endovascular treatment was significantly better than surgery in avoiding cranial neuropathy (OR 0.15) and myocardial infarction (OR 0.34). There was no significant difference between endovascular treatment and surgery in the following comparisons: 30-day stroke, MI, or death (OR 1.12); 30-day disabling stroke or death (OR 1.19); 30-day death (OR 0.99); 24-month death or stroke (OR 1.26); and 30-day death or stroke in endovascular patients treated with or without protection devices (OR 0.75). CONCLUSIONS: The data are difficult to interpret because the trials are heterogeneous. Five trials were stopped early, perhaps leading to an overestimate of the risks of endovascular treatment. The results do not support a change in clinical practice away from recommending carotid endarterectomy as the treatment of choice for suitable carotid artery stenosis but support continued recruitment in the large ongoing trials.

Vascular intervention in stroke prevention: endarterectomy and angioplasty.

Carotid stenosis is a major risk factor for stroke and transient ischaemic attack. Asymptomatic and symptomatic carotid stenoses need to be considered separately. Carotid endarterectomy was established as the treatment of choice for recently symptomatic severe carotid stenosis by two landmark trials. The effect of surgery is much less in patients with moderate carotid stenosis and harmful in patients with stenosis of less than 50%. Suitable patients should be operated on within 2 weeks of symptoms because the benefit of endarterectomy declines rapidly with increasing time between symptom onset and treatment. The benefits of endarterectomy for asymptomatic stenosis shown in the randomised trials were much less. Improvements in medical treatment, especially increasing statin use after the trials were started, need to be taken into consideration when interpreting the trials, and most neurologists conclude that routine endarterectomy for asymptomatic stenosis is not justified. Early trials of endovascular treatment of carotid stenosis suggested that endovascular treatment might be a safe and effective alternative to carotid endarterectomy. However, subsequent trials have so far failed to provide enough evidence to justify routine carotid stenting as an alternative to endarterectomy in patients fit for surgery. More data from ongoing randomised trials of stenting versus endarterectomy are needed to determine the role of stenting in the treatment of carotid stenosis.

Long-term outcome of endovascular treatment versus medical care for carotid artery stenosis in patients not suitable for surgery and randomised in the Carotid and Vertebral Artery Transluminal Angioplasty study (CAVATAS).

BACKGROUND: Optimal treatment of carotid stenosis in patients not suitable for surgery is unclear. The Carotid and Vertebral Artery Transluminal Angioplasty study contained a trial comparing medical and endovascular treatment in patients not suitable for surgery. METHODS: Forty patients were randomised to medical or endovascular treatment in equal numbers, and patients were followed up for up to 10 years. The primary outcome measure was defined as stroke or death during follow-up, analysed by intention-to-treat. Secondary analyses included disabling stroke, death, any stroke, any stroke or transient ischemic attack (TIA), all during follow-up. FINDINGS: Baseline characteristics were similar. The risk of stroke, retinal infarction or death within 30 days of endovascular treatment was 5% (95% CI: 0.1-24.9%). By the study end, >50% of patients had suffered a recurrent TIA, stroke or died. One third of events were non-stroke deaths. Overall, there was no significant difference between medical and endovascular treatment in the primary outcome rate of stroke or death after randomisation (hazard ratio: 0.98, 95% CI: 0.39-2.48) or the rate of any stroke or TIA (hazard ratio: 1.43, 95% CI: 0.54-3.75). INTERPRETATION: We failed to show superiority of endovascular treatment above medical care alone for carotid stenosis in a very small group of patients not suitable for surgical treatment. However, the trial randomised only 40 patients, and was therefore severely underpowered to detect clinically relevant treatment differences. Ongoing trials of carotid stenting will need to demonstrate improved safety and efficacy before endovascular treatment should enter routine practice.

Stroke prevention.

Stroke is one of the leading causes of death and disability in the Western world and efforts should be made to prevent the occurrence of stroke. Primary preventive measures are influenced by the patient's risk factor profile. A healthy lifestyle should be encouraged. Hypertension as a major risk factor for stroke should be controlled either by lifestyle measures or, if that is unsuccessful, through pharmacological means. The risk of stroke in diabetic patients with hypertension is increased and blood pressure and blood sugar levels should be controlled. Atrial fibrillation increases the risk of stroke and in high-risk patients oral anticoagulation is recommended. Patients suffering from coronary artery disease and high-risk hypertensive patients should be treated with statins. Asymptomatic carotid artery disease increases the risk of stroke. Before surgery is considered, it is important to optimize medical treatment of vascular risk factors. In addition to these measures, secondary prevention of stroke includes the prescription of antiplatelet therapy. Oral anticoagulation should be reserved for cardioembolic strokes. Symptomatic carotid stenosis should be treated by carotid endarterectomy. Stenting should be reserved for patients with contraindications to surgery or in the setting of clinical randomized trials.

The evidence for medicine versus surgery for carotid stenosis.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. Several large randomised trials have compared best medical management with carotid endarterectomy and provide a strong evidence base for advising and selecting patients for carotid surgery. Best medical management of carotid stenosis includes lowering of blood pressure, treatment with statins and antiplatelet therapy in symptomatic patients. Combined analysis of the symptomatic carotid surgery trials, together with observational data, has shown that patients with recently symptomatic severe carotid stenosis have a very high risk of recurrent stroke in the first few days and weeks after symptoms. Carotid endarterectomy has a risk of causing stroke or death at the time of surgery in symptomatic patients of around 5-7%, but in patients with recently symptomatic stenosis of more than 70%, the benefits of endarterectomy outweigh the risks. In patients with moderate stenosis of between 50 and 69%, the benefits may justify surgery in patients with very recent symptoms, and in patients older than 75 years within a few months of symptoms. Patients with less than 50% stenosis do not benefit from surgery. In asymptomatic patients, or those whose symptoms occurred more than 6 months ago, the benefits of surgery are considerably less. Patients with asymptomatic stenosis treated medically only have a small risk of future stroke when treated medically of about 2% per annum. If carotid endarterectomy can be performed safely with a perioperative stroke and death rate of no more than 3%, then the randomised trials showed a significant benefit of surgery over 5 years follow-up, with an overall reduction in the risk of stroke from about 11% over 5 years down to 6%. However, of 100 patients operated, only 5 will benefit from avoiding a stroke over 5 years. The majority of neurologists have concluded that this does not justify a policy of routine screening and endarterectomy for asymptomatic stenosis. Patients known to have asymptomatic stenosis should be advised of the risks and benefits. The trials provide justification for surgery at centres with a proven low complication rate, in asymptomatic patients prepared to take a small immediate risk in exchange for a small longer term benefit. Those that opt for medical management alone should be advised to seek urgent medical attention should they become symptomatic in the future.

Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): a randomised controlled trial with cost-effectiveness analysis.

BACKGROUND: Carotid artery stenting (CAS) is an alternative to carotid endarterectomy (CEA) for the treatment of carotid stenosis, but safety and long-term efficacy were uncertain. OBJECTIVE: To compare the risks, benefits and cost-effectiveness of CAS versus CEA for symptomatic carotid stenosis. DESIGN: International, multicentre, randomised controlled, open, prospective clinical trial. SETTING: Hospitals at 50 centres worldwide. PARTICIPANTS: Patients older than 40 years of age with symptomatic atheromatous carotid artery stenosis. INTERVENTIONS: Patients were randomly allocated stenting or endarterectomy using a computerised service and followed for up to 10 years. MAIN OUTCOME MEASURES: The primary outcome measure was the long-term rate of fatal or disabling stroke, analysed by intention to treat (ITT). Disability was assessed using the modified Rankin Scale (mRS). A cost-utility analysis estimating mean costs and quality-adjusted life-years (QALYs) was calculated over a 5-year time horizon. RESULTS: A total of 1713 patients were randomised but three withdrew consent immediately, leaving 1710 for ITT analysis (853 were assigned to stenting and 857 were assigned to endarterectomy). The incidence of stroke, death or procedural myocardial infarction (MI) within 120 days of treatment was 8.5% in the CAS group versus 5.2% in the CEA group (72 vs. 44 events) [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.16 to 2.45; p = 0.006]. In the analysis restricted to patients who completed stenting, age independently predicted the risk of stroke, death or MI within 30 days of CAS (relative risk increase 1.17% per 5 years of age, 95% CI 1.01% to 1.37%). Use of an open-cell stent conferred higher risk than a closed-cell stent (relative risk 1.92, 95% CI 1.11 to 3.33), but use of a cerebral protection device did not modify the risk. CAS was associated with a higher risk of stroke in patients with an age-related white-matter changes score of 7 or more (HR 2.98, 95% CI 1.29 to 6.93; p = 0.011). After completion of follow-up with a median of 4.2 years, the number of patients with fatal or disabling stroke in the CAS and CEA groups (52 vs. 49), and the cumulative 5-year risk did not differ significantly (6.4% vs. 6.5%) (HR 1.06, 95% CI 0.72 to 1.57; p = 0.776). Stroke of any severity was more frequent in the CAS group (15.2% vs. 9.4% in the CEA group) (HR 1.712, 95% CI 1.280 to 2.300; p < 0.001). There was no significant difference in long-term rates of severe carotid restenosis or occlusion (10.8% in the CAS group vs. 8.6% in the CEA group) (HR 1.25, 95% CI 0.89 to 1.75; p = 0.20). There was no difference in the distribution of mRS scores at 1-year, 5-year or final follow-up. There were no differences in costs or QALYs between the treatments. LIMITATIONS: Patients and investigators were not blinded to treatment allocation. Interventionists' experience of stenting was less than that of surgeons with endarterectomy. Data on costs of managing strokes were not collected. CONCLUSIONS: The functional outcome after stenting is similar to endarterectomy, but stenting is associated with a small increase in the risk of non-disabling stroke. The choice between stenting and endarterectomy should take into account the procedural risks related to individual patient characteristics. Future studies should include measurement of cognitive function, assessment of carotid plaque morphology and identification of clinical characteristics that determine benefit from revascularisation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25337470. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 20. See the NIHR Journal Library website for further project information. Further funding was provided by the Medical Research Council, Stroke Association, Sanofi-Synthélabo and the European Union.

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials.

Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.

BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.

Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial.

BACKGROUND: Endovascular treatment (angioplasty with or without stenting) is an alternative to carotid endarterectomy for carotid artery stenosis but there are scarce long-term efficacy data showing that it prevents stroke. We therefore report the long-term results of the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). METHODS: Between March, 1992, and July, 1997, patients who presented at a participating centre with a confirmed stenosis of the internal carotid artery that was deemed equally suitable for either carotid endarterectomy or endovascular treatment were randomly assigned to either treatment in equal proportions by telephone or fax from the randomisation service at the Oxford Clinical Trials Unit, UK. Patients were seen by an independent neurologist at 1 and 6 months after treatment and then every year after randomisation for as long as possible, up to a maximum of 11 years. Major outcome events were transient ischaemic attack, non-disabling, disabling, and fatal stroke, myocardial infarction, and death from any other cause. Outcomes were adjudicated on by investigators who were masked to treatment. Analysis was by intention to treat. This study is registered, number ISRCTN 01425573. FINDINGS: 504 patients with stenosis of the carotid artery (90% symptomatic) were randomly assigned to endovascular treatment (n=251) or surgery (n=253). Within 30 days of treatment, there were more minor strokes that lasted less than 7 days in the endovascular group (8 vs 1) but the number of other strokes in any territory or death was the same (25 vs 25). There were more cranial nerve palsies (22 vs 0) in the endarterectomy group than in the endovascular group. Median length of follow up in both groups was 5 years (IQR 2-6). By comparing endovascular treatment with endarterectomy after the 30-day post-treatment period, the 8-year incidence and hazard ratio (HR) at the end of follow-up for ipsilateral non-perioperative stroke was 11.3% versus 8.6% (HR 1.22, 95% CI 0.59-2.54); for ipsilateral non-perioperative stroke or TIA was 19.3% versus 17.2% (1.29, 0.78-2.14); and for any non-perioperative stroke was 21.1% versus 15.4% (1.66, 0.99-2.80). INTERPRETATION: More patients had stroke during follow-up in the endovascular group than in the surgical group, but the rate of ipsilateral non-perioperative stroke was low in both groups and none of the differences in the stroke outcome measures was significant. However, the study was underpowered and the confidence intervals were wide. More long-term data are needed from the on going stenting versus endarterectomy trials. FUNDING: British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.

Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial.

BACKGROUND: In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), early recurrent carotid stenosis was more common in patients assigned to endovascular treatment than it was in patients assigned to endarterectomy (CEA), raising concerns about the long-term effectiveness of endovascular treatment. We aimed to investigate the long-term risks of restenosis in patients included in CAVATAS. METHODS: 413 patients who were randomly assigned in CAVATAS and completed treatment for carotid stenosis (200 patients had endovascular treatment and 213 patients had endarterectomy) had prospective clinical follow-up at a median of 5 years and carotid duplex ultrasound at a median of 4 years. We investigated the cumulative long-term incidence of carotid restenosis after endovascular treatment and endarterectomy, the effect of the use of stents on restenosis after endovascular treatment, risk factors for the development of restenosis, and the effect of carotid restenosis on the risk of recurrent cerebrovascular events. Analysis was by intention to treat. This study is registered, number ISRCTN01425573. FINDINGS: Severe carotid restenosis (>or=70%) or occlusion occurred significantly more often in patients in the endovascular arm than in patients in the endarterectomy arm (adjusted hazard ratio [HR] 3.17, 95% CI 1.89-5.32; p<0.0001). The estimated 5-year incidence of restenosis was 30.7% in the endovascular arm and 10.5% in the endarterectomy arm. Patients in the endovascular arm who were treated with a stent (n=50) had a significantly lower risk of developing restenosis of 70% or greater compared with those treated with balloon angioplasty alone (n=145; HR 0.43, 0.19-0.97; p=0.04). Current smoking or a history of smoking was a predictor of restenosis of 70% or more (2.32, 1.19-4.54; p=0.01) and the early finding of moderate stenosis (50-69%) up to 60 days after treatment was associated with the risk of progression to restenosis of 70% or more (3.76, 1.88-7.52; p=0.0002). The composite endpoint of ipsilateral non-perioperative stroke or transient ischaemic attack occurred more often in patients in whom restenosis of 70% or more was diagnosed in the first year after treatment compared with patients without restenosis of 70% or more (5-year incidence 23%vs 11%; HR 2.18, 1.04-4.54; p=0.04), but the increase in ipsilateral stroke alone was not significant (10%vs 5%; 1.67, 0.54-5.11). INTERPRETATION: Restenosis is about three times more common after endovascular treatment than after endarterectomy and is associated with recurrent ipsilateral cerebrovascular symptoms; however, the risk of recurrent ipsilateral stroke is low. Further data are required from on-going trials of stenting versus endarterectomy to ascertain whether long-term ultrasound follow-up is necessary after carotid revascularisation. FUNDING: British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.