CREST: Stenting and endarterectomy show similar net safety and efficacy for carotid stenosis

Susan Jeffrey

February 26, 2010

San Antonio, TX(updated) - Final results of the long-awaited Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) show similar net outcomes with carotid artery stenting (CAS) and carotid endarterectomy (CEA) for the treatment of carotid stenosis, researchers report[1]. The results were presented here at the American Stroke Association International Stroke Conference 2010.

CREST is the largest prospective randomized trial to date comparing these two interventions, with 2502 patients from 117 US and Canadian centers.

On the composite primary end point of any stroke, MI, or death during the periprocedural period or ipsilateral stroke on follow-up, stenting was associated with a 7.2% rate of these events vs 6.8% with surgery, a nonsignificant difference.

However, individual risks varied, they found. At 30 days, the rate of stroke was significantly higher with stenting, at 4.1% vs 2.3% with surgery. Major stroke, though, was not different, at less than 1% in both groups. Conversely, MI was higher with carotid endarterectomy, at 2.3% vs 1.1% with stenting, again a statistically significant difference.

Patients who had an MI, however, reported a better quality of life after recovery than those who had a stroke, the authors noted.

Rates of ipsilateral stroke during a mean follow-up of 2.5 years were equal between groups, at 2.0% for stenting and 2.4% with surgery.

Dr Wayne Clark

Dr Wayne Clark (Oregon Health Sciences University, Portland) was principal investigator from the lead enrolling center for CREST and presented the findings here on behalf of the CREST investigators. He pointed out that the event rates in this trial were lower than have been seen in prior studies, something he credited to the rigorous credentialing process and lead-in phase for operators in this study.

"I think both procedures are excellent, with low perioperative rates and apparently excellent clinical durability, so I'm excited to say that I think we have two good options to treat patients," Clark told reporters here.

Differences in outcomes by age

Dr Thomas G Brott

There were also differences seen in outcome with age, the investigators reported. During the lead-in phase, it was noticed there was a higher risk of events for older patients with stenting, said principal investigator Dr Thomas G Brott (Mayo Clinic, Jacksonville, FL).

That higher event rate was also seen in the randomized trial, with those approximately 69 years of age and older having better outcomes with surgery, and those younger than 69 having slightly better outcomes with stenting.

"When we went into this, I think we thought the less invasive procedure would be best suited for the older patient," Brott said. "Now that we have data from studies in the US and Europe, we have to question that."

Although they did not present the data in detail here, Clark did note that outcomes were also similar for symptomatic and asymptomatic patients and for men and women in this trial.

"CAS may offer a reasonable alternative to CEA, particularly in patients who prefer a less invasive procedure and in younger patients," Dr Wesley S Moore (University of California, Los Angeles), a surgeon and co-principal investigator, concluded in a statement from the National Institutes of Health (NIH)[2].

"However, it should be kept in mind that for the end point of stroke, CEA has been shown to be the safer procedure. It is when heart attacks are added that the results of the two procedures become similar," Moore added.

Lead-in phase

CREST compared CAS and CEA for stroke prevention in patients with both asymptomatic and symptomatic extracranial carotid stenosis. The trial was preceded by an NIH-funded lead-in phase meant to credential interventionalists in what was at the time the fairly new and evolving technology of carotid stenting.

The study included 1321 symptomatic and 1181 asymptomatic patients, who were randomized to receive either stenting using the same stent and distal-protection devices (Acculink and Accunet, Abbott Vascular, Redwood City, CA) or carotid endarterectomy. Subjects were 35% female, and only 9.3% were minorities.

Patients with symptomatic stenosis had a >50% stenosis by angiography or >70% by ultrasound or computed tomography/magnetic resonance angiography (CT/MRA), a newer imaging technique that was used later in the trial for enrollment purposes. Asymptomatic patients had lesions of >60% by angiography, >70% by ultrasound, or >80% on CT/MRA.

Again, the primary end point was a composite of clinical stroke, MI, or death during the periprocedural period plus ipsilateral stroke on the vessel that was treated, with patients followed out to four years. End points were blindly adjudicated by two independent neurologists.

Enrollment in the CREST trial began with symptomatic patients only but was slow at the outset, Clark noted. "We started very slowly there, and I think early on there were concerns that we'd ever finish," he said. "As we added more sites, things got better, and at about the midpoint of the trial, we decided also to include asymptomatic patients."

The patients were well matched for age, risk factors, and degree of stenosis, he noted, with more than 85% of patients in both groups having stenoses of >70%.

"Again, overall on the primary end point—stroke, MI, death periprocedurally plus ipsilateral stroke out to four years—there was no significant difference between the two treatment groups," he said. Kaplan-Meier curves confirmed most events were periprocedural.

CREST: Primary, secondary and safety end points

End point CAS CEA Hazard ratio (95% CI) p
Primary end point <4 y 7.2 6.8 1.11 (0.81-1.51) 0.51
Primary end point : Periprocedural components 5.2 4.5 1.18 (0.82-1.68) 0.38
Periprocedural stroke and MI        
Any periprocedural stroke 4.1 2.3 1.79 (1.14-2.82) 0.01
Periprocedural major stroke 0.9 0.7 1.35 (0.54-3.36) 0.52
Periprocedural MI 1.1 2.3 0.50 (0.26-0.94) 0.03
Cranial nerve palsies 0.3 4.8 0.07 (0.02-0.18) 0.0001
Ipsilateral stroke after periprocedural period <4 y 2.0 2.4 0.94 (0.50-1.76) 0.85
CAS=carotid artery stenting
CEA=carotid endarterectomy

Further analysis of the quality-of-life data and economic data from CREST is ongoing and will be presented in the future, Clark added.

"Now, to paraphrase Marc Antony, I come here today not to bury carotid endarterectomy but to praise it," he concluded wryly. "As such, at experienced centers, I think our results show that both procedures have very low perioperative complication rates and excellent long-term results. I feel we now have two options that we can offer to our patients to prevent them having carotid artery strokes."

At odds with ICSS?

During the question period, Clark was asked how the CREST researchers explain the difference between their findings and those published only the day before in the Lancet from the International Carotid Stenting Study (ICSS). In that paper, interim safety results at 120 days appeared to favor carotid endarterectomy over carotid stenting for patients with symptomatic carotid stenosis only.

The ICSS results showed higher rates of stroke, death, or periprocedural MI in patients treated with stenting vs endarterectomy. The primary outcome of that study is the three-year rate of fatal or disabling stroke in any territory, and results are expected in 2012.

"I think the Lancet results do point out that, whether it's tPA past three hours or carotid artery stenting, different results and sometimes conflicting results can occur between European and US trials," Clark replied.

CREST had a very detailed credentialing process, he added, and the almost 1600 practice cases done during this period, whether they were proctored or not, were not included in the randomized CREST trial. "So you can make your own inference on why I think the results might be different," he said.

In an interview, ICSS principal investigator Dr Martin M Brown (University College London, UK) acknowledged that the CREST investigators had stricter criteria for investigators to join the trial, which might have made some difference, but thought it was probably more likely to be related to the mix of patients. CREST had both symptomatic and asymptomatic patients, while ICSS included only symptomatic patients.

"We may need to wait until they do the analysis of just their symptomatic patients to know whether it closely matches our trial or not," he said. "I think there'll be a lot more interesting analysis coming out of the trial, and we're hoping to combine all our data together with the CREST results in due course so that we can look at different risk factors."

"The CREST trial provides doctors and patients with much-needed risk/benefit information to help choose the best carotid procedure based on an individual's health history," said Dr Walter J Koroshetz, deputy director of National Institute of Neurological Disorders and Stroke, in the NIH statement. "This personalized decision making should translate into improved patient outcomes."

The study was supported by the National Institute of Neurological Disorders and Stroke with supplemental funding by Abbott. The investigators report no conflicts of interest.

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