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

Abstract

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.

Figure 1

Trial profile

Figure 2

Kaplan–Meier estimates of cumulative incidence The numbers above and below the lines refer to the 8-year incidence (SE) (%). (A) Disabling stroke or death (primary outcome measure). (B) Any stroke or perioperative death. (C) Stroke that lasted more than 7 days or perioperative death within 30 days of treatment. (D) Non-perioperative stroke or TIA. (E) Non-perioperative stroke. (F) Non-perioperative ipsilateral stroke or transient ischaemic attack. (G) Non-perioperative ipsilateral stroke. (H) Any cause of death. Except where stated, stroke refers to events in any territory. A, B, C, and H are analysed from date of randomisation; D and G are analysed from 30 days after treatment. No stroke that occurred more than 30 days after treatment lasted for fewer than 7 days.

Figure 3

Subgroup analysis to compare the rates of the outcome event of stroke in any territory that lasted more than 7 days or perioperative death, according to various baseline characteristics p values are associated with treatment–covariate interaction tests. The dotted vertical line is the hazard ratio in the overall population. Analyses are by intention to treat. n=number of events. N=number of patients in each group. EVT=endovascular treatment. CEA=carotid endarterectomy. HR=hazard ratio. TIA=transient ischaemic attack. MI=myocardial infarction.

Figure 4

Meta-analysis of the main multicentre randomised controlled trials Comparison of long-term benefit of endovascular treatment versus endarterectomy for symptomatic carotid artery stenosis in prevention of non-perioperative ipsilateral stroke. The summary estimate statistic is a Peto odds ratio (fixed-effect model), the centre of the diamond is the point estimate, and the ends of the line are the 95% CI. The I-square statistic gives an indication of heterogeneity, where 0% suggests that it might not be important. The value of I-squared depends on the magnitude and direction of effects and the strength of evidence for heterogeneity (p value from χ² test).