Women in CREST: Higher Stroke Rate With Carotid Stenting vs Surgery

Allison Gandey

September 15, 2010

September 15, 2010 (San Francisco, California) — In a new subgroup analysis of CREST — the Carotid Revascularization Endarterectomy versus Stenting Trial — investigators report that the composite primary outcome of any stroke, myocardial infarction, or death in 30 days or ipsilateral stroke on follow-up among both symptomatic and asymptomatic women was similar between groups.

Stroke rate higher in women receiving stents.

However, perioperative stroke was significantly higher among women patients who underwent carotid stenting vs carotid endarterectomy.

"Neurologists should put the sex of the patient into the mix when they decide the best treatment for them," lead investigator Helmi Lutsep, MD, from the Oregon Health and Science University in Portland, told Medscape Medical News. "However, I don't think that we're ready to say that carotid stenting should be entirely avoided in women."

In the original trial, Dr. Lutsep points out, the primary outcome did not differ between men and women, despite the higher rate of periprocedural strokes in women in the stenting group reported here.

"I was a little surprised to see the slight increased stroke risk among women," presenter Rafael Llinàs, MD, from Johns Hopkins University in Baltimore, Maryland, said during an interview. "I had assumed the funny idea that there's not that much difference between men and women."

Dr. Llinàs speculates that the higher stroke risk in women may relate to the surgical challenge of manipulating smaller arteries. "This is probably the case, although it's difficult to know," he said.

The subanalysis was presented here at the American Neurological Association 135th Annual Meeting.

Higher Stroke

CREST is the largest prospective randomized trial to date comparing these interventions, with 2502 patients from 117 US and Canadian centers. Patients received the same stent and distal protection devices (Acculink and Accunet devices; Guidant Corporation) or underwent endarterectomy. Subjects were 35% women; only 9.3% were minorities.

In this analysis, the authors presented data comparing these modalities in the 872 women enrolled in CREST.

There was no difference seen in the composite primary endpoint between stenting and endarterectomy, although events were numerically higher with stenting and symptomatic status. It "did not alter this finding," report the researchers.

Within 30 days of the procedure, significantly more primary endpoint events occurred with stenting.

In the original study, overall primary outcome events were similar, but individual risks varied: Patients in the stenting group had more strokes, whereas those receiving surgery had more myocardial infarctions. In this analysis, the rate of periprocedural myocardial infarction for women was similar regardless of the procedure, but periprocedural stroke risk was significantly higher with stenting.

Rates of ipsilateral stroke though were similar up to 4 years later. The numbers were 2.2% for those with stenting vs 3.0% in surgical patients (P = .29).

If artery size is playing a role in the risk of stroke, this could have worrisome implications for other, less specialized centers. CREST surgeons underwent a very detailed credentialing process with strict criteria to join the trial. If highly skilled and prescreened surgeons had higher adverse event rates, it is not clear what numbers other less experienced surgeons might have, perhaps changing the risk benefit ratio considerably. Dr. Llinàs acknowledges this could be a concern.

Women and Stenting

Martin M. Brown, from the Institute of Neurology at the University College London in England, served as principal investigator of the International Carotid Stenting Study (ICSS). He is also corresponding author of a recently reported meta-analysis of the ICSS findings with 2 other large European trials comparing stenting and surgery. The studies are known as SPACE (Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy) and EVA-3S (Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis) (Lancet. Published online September 10, 2010).

Asked by Medscape Medical News to comment on this new CREST analysis, Prof. Brown said they had also found a slightly higher risk with stenting vs surgery for women in the recently reported meta-analysis but notes he finds it difficult to interpret CREST results in general because they often combine results from symptomatic and asymptomatic patients, as they have done in this presentation.

Those with and without symptoms, he said, "have such different outcomes and such different risks that it doesn't make any sense to combine them at all."

Still, he said, the primary endpoint and stroke risk reported here is "quite a bit higher" than endarterectomy. "They're going to have to conclude I suppose that it's not appropriate to treat women with stenting at all."

An interesting calculation that could be made both with their own and the CREST data would be to calculate the combined effect of age and sex on outcomes. "What we ought to do — and we haven't done this because you end up with rather a small group of patients — is look at young men vs old men and younger women vs older women."

Both CREST and the Carotid Stenting Trialists' Collaboration meta-analysis showed a strong effect of increasing age on the risk for endpoint events with stenting.

Dr. Lutsep added, "We are currently investigating risk factors that may be different in women enrolled in CREST compared to the men, but don't have a final answer on the age question — it is certainly something we'll be looking at."

Presenter Bias

In a recent Medscape Viewpoints , Frank Veith, MD, from the New York University Medical Center, New York City, raised concerns about what he calls the spinning of CREST.

CREST, he says, was designed and conducted in an exemplary manner. "It has attracted a great deal of attention, and its findings should be part of a solid and definitive basis for determining medical practice. Yet, when the findings of CREST have been presented, the conclusions differ greatly, depending on the bias of the presenter."

If a vascular specialist with a bias toward carotid endarterectomy interprets the CREST findings, the lower stroke and mortality rates justify the conclusion that surgery is superior and should be used preferentially to treat patients who require an invasive procedure for carotid stenosis.

In contrast, Dr. Veith points out, if a vascular specialist with a bias toward carotid stenting interprets the findings, he or she will regard them as definitive and will conclude that the equivalent and low overall adverse event rates for the 2 procedures justify the widespread and increased use of stenting to treat patients who have symptomatic or asymptomatic carotid stenosis.

"The extent to which the preliminary results of CREST are being spun should be recognized," Dr. Veith notes. "The truth lies somewhere in between these 2 diametrically opposed views."

The take-home message from CREST, Mark Alberts, MD, says in a Medscape Video Blog , is that the 2 interventions are roughly equivalent, with some tradeoffs in terms of stroke among men and women and myocardial infarction in men. Dr. Alberts is director of the stroke program at Northwestern Memorial Hospital in Chicago, Illinois.

Editorialists Sticking With Surgery

In an editorial accompanying the published CREST results, Dr. Stephen Davis and Dr. Geoffrey Donnan from the University of Melbourne in Australia say that for now, surgery is their treatment of choice, at least for patients with symptomatic carotid stenosis (N Engl J Med. 2010;363:80-82).

Despite being among the largest of the randomized trials, with what they call "impressively low complication rates," results of CREST in the periprocedural period are similar to those seen in previous trials of symptomatic patients.

The editorialists suggest, "The crux of the debate about the CREST results is this: Can periprocedural stroke and myocardial infarction be considered equivalent events in terms of longer-term health implications? We think not." Post hoc analyses of health status at 1 year using the 36-item Short-Form Health Survey summary scales confirmed that major and minor stroke had effects on physical and mental health. Myocardial infarction did not.

In the end, the risk–benefit issue is complex, the editorialists argue, and should be discussed with patients. "We conclude that until more data are available, carotid endarterectomy remains the preferred treatment for most patients with symptomatic carotid stenosis; treatment for asymptomatic stenosis remains controversial. However, given the lack of significant difference in the rate of long-term outcomes, the individualization of treatment choices is appropriate."

This study was supported by the National Institute of Neurological Disorders and Stroke, with additional support by Abbott Vascular Solutions.

American Neurological Association 135th Annual Meeting: Poster M-1. Presented September 13, 2010.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.