An interim safety analysis of the ongoing International Carotid Stenting Study (ICSS) offers strong temporary evidence that carotid endarterectomy is preferable to carotid stenting. In a paper appearing in the Lancet, the ICSS investigators report on the incidence of stroke, death, or procedural MI in the 1,713 patients enrolled in the trial. In the carotid stenting group the rate was 8.5% (72 events) versus 5.2% (44 events) in the endarterectomy group (HR 1.69, 1.16-2.45, p=0.006).

The results, write the authors, “suggest that carotid endarterectomy should remain the treatment of choice for symptomatic patients with severe carotid stenosis suitable for surgery.” However, they note that “stenting is also likely to be better than no revascularization in patients unwilling or unable to have surgery because of medical or anatomical contraindications.” The primary endpoint of the ongoing trial is the 3-year rate of fatal or disabling stroke in any territory.

In a second paper, appearing in Lancet Neurology, the ICSS-MRI study group reports the results of an MRI substudy in 231 patients.  Due to the possibility of an ascertainment bias in the main trial caused by the fact that investigators were aware of the treatment received by study subjects, the substudy was performed to obtain an objective, blinded analysis of the rate of ischemic brain injury. One day after treatment new ischemic lesions were found in 50% of the stenting group versus 17% of the endarterectomy group. Cerebral protection devices did not improve outcome in the stenting group.

Here is the Lancet press release:

CAROTID STENTING NOT AS EFFECTIVE AT PREVENTING STROKE OR AS SAFE AS STANDARD SURGERY IN THE SHORT-TERM

Carotid endarterectomy (CEA), surgery that removes material causing the narrowing of the artery that supplies blood to the brain, is safer than implantation of a carotid artery stent, in which a wire mesh stent is inserted to hold open the artery, as a treatment for carotid blockages that can lead to stroke. Surgery almost halves the risk of stroke and death within 30 days after treatment compared to stenting, and significantly reduces the risk of stroke, death, and treatment-related heart attacks in the first few months after diagnosis. These are the findings of two Articles published Online First in The Lancet and The Lancet Neurology.

The standard treatment for symptomatic carotid stenosis (narrowing of the arteries that supply blood to the brain), one of the main causes of stroke, is surgery (endarterectomy) to remove fatty deposits via an incision in the neck. Stenting, a less invasive treatment which does not require general anaesthesia, and has potentially fewer complications and a faster recovery time, is also used as an alternative treatment option. However, although studies comparing CEA and carotid artery stenting (CAS) have been published, none have established whether stenting is equivalent to surgery in terms of safety and efficacy.

The International Carotid Stenting Study (ICSS) investigators assessed the effectiveness of stenting and endarterectomy at preventing stroke, death, and procedure-related heart attacks in 1713 patients with recently symptomatic carotid stenosis. Patients were randomly assigned to stenting (n=855) or surgery (n=858) and followed for up to 120 days after randomisation.

Findings showed that patients in the stent group had a significantly greater risk of stroke, death, or procedure-related heart attack within 120 days of randomisation—absolute risk 8.5% compared with 5.2% in the surgery group. Additionally, within 30 days of treatment the rate of stroke or death in the stent group was nearly twice the rate recorded in the surgery group. This difference was mainly due to a higher number of non-disabling strokes recorded in the stent group (36 vs 11 within 30 days of treatment), whereas the number of disabling strokes or deaths did not differ significantly (26 vs 18).

The authors conclude: “Completion of long-term follow-up is needed to establish the efficacy of treatment with a carotid artery stent compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for symptomatic patients suitable for surgery.”

Because investigators who assessed patients during follow-up were not blinded to treatment allocation, there was the possibility of ascertainment bias (distortion of the results) which might explain the higher incidence of non-disabling strokes found in the stent group. Therefore the second Article, published in The Lancet Neurology, reports a blinded analysis of the ICSS trial to assess the rate of ischaemic brain injury on MRI after treatment in the two groups.

231 patients (124 from the stenting group and 107 from the surgery group) had MRI scans before and after treatment which were assessed by investigators who were masked to treatment.

MRI results showed that about three times as many patients had new ischaemic lesions after stenting than after surgery (50% vs 17%).

The authors conclude that these neuroimaging data confirm that carotid surgery is safer then carotid stenting. They point out that the increased risk of non-disabling stroke after stent treatment is unlikely to have been caused by ascertainment bias. Most of the new ischaemic lesions were not associated with symptoms of stroke at the time of stenting and the authors suggest that the most likely explanation is that particles of atheromatous plaque are released during implantation of the stent, which are too small to cause any noticeable symptoms at the time but nevertheless lead to small areas of brain damage.