Study Shows Stroke Risk Higher for Women with Stents

 

Stroke Risk Higher in Women

In a new subgroup analysis of the Carid Reotvascularization Endarterectomy versus Stenting Trial (CREST), investigators report that the composite primary outcome of any stroke, MI, or death in 30 days or ipsilateral stroke on follow-up among both symptomatic and asymptomatic women was similar between groups.

However, perioperative stroke was significantly higher among female 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 Dr Helmi Lutsep (Oregon Health and Science University, Portland) said in an interview. “However, I don’t think that we’re ready to say that carotid stenting should be entirely avoided in women.”

In the original trial, 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 Dr Rafael Llinàs (Johns Hopkins Medicine, Baltimore, MD) said during an interview. “I had assumed the funny idea that there’s not that much difference between men and women.”

Llinàs speculates that the higher stroke risk in women may relate to the challenge of navigating and manipulating devices in smaller arteries. “This is probably the case, although it’s difficult to know,” he said.

The main results of CREST were published July 1, 2010 in the New England Journal of Medicine.The subanalysis was presented here at the American Neurological Association 2010 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, Abbot Vascular) or underwent endarterectomy. Subjects were 35% female, and only 9.3% were minorities.

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

There was no difference seen in the composite primary end point 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 end-point 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, while those receiving surgery had more MIs. In this analysis, the rate of periprocedural MI 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 four years later. The numbers were 2.2% for those with stenting vs 3.0% in surgical patients (p=0.29).

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’s not clear what numbers other, less experienced, surgeons might have, perhaps changing the risk/benefit ratio considerably. Llinàs acknowledges this could be a concern.
Editorialists sticking with surgery

In an editorial accompanying the published CREST results, Drs Stephen Davis and Geoffrey Donnan (University of Melbourne, Australia) say that for now surgery is their treatment of choice, at least for patients with symptomatic carotid stenosis.

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.

Trials include the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S), the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and, more recently, the International Carotid Stenting Study (ICSS).

A meta-analysis of these three trials, published online September 10, 2010 in the Lancet, found a similar differential in outcomes by age, as was observed in CREST. The Carotid Stenting Trialists’ Collaboration concludes, “Stenting for symptomatic carotid stenosis should be avoided in older patients (age >70 years) but might be as safe as endarterectomy in younger patients.”

Lutsep said, “We are currently investigating risk factors that may be different in women enrolled in CREST compared with the men, but don’t have a final answer for you on the age question—it is certainly something we’ll be looking at.”

The editorialists say, “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 one year using the 36-Item Short-Form Health Survey summary scales confirmed that major and minor stroke had effects on physical and mental health. MI did not.

In the end, the risk/benefit issue is complex, they 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.”