ACT I, CREST Support Carotid Stenting as Alternative to Surgery, but Larger Question Looms

LOS ANGELES—Carotid artery stenting holds up well over the long term against endarterectomy in asymptomatic and symptomatic patients with severe carotid stenosis, according to results from the ACT I and CREST trials presented at the International Stroke Conference here. But neither trial can address whether either procedure is needed in an era when stroke rates are falling due to more aggressive medical therapy.

Researchers hope that question will be answered by the ongoing CREST-2 trial, which is actually 2 separate trials comparing either stenting or endarterectomy plus intensive medical management to intensive medical management alone in patients with asymptomatic high-grade carotid stenosis.

It is known that the incidence of stroke has declined with improvements in preventive medications, Kenneth Rosenfield, MD, of Massachusetts General Hospital (Boston, MA), one of the principal investigators of ACT I, told TCTMD. “The question is does medical therapy reduce it enough to mitigate the benefits of revascularization in a patient with a tight carotid artery stenosis,” he said.

He said he hopes CREST-2 will clarify the issue, adding that it depends on enrolling enough patients and a population that is representative enough for the findings to be generalizable to a wide range of patients with asymptomatic severe carotid disease.

Both the ACT I and CREST findings were published simultaneously online in the New England Journal of Medicine.

ACT I

Lawrence Wechsler, MD, of the University of Pittsburgh Medical Center (Pittsburgh, PA), presented the results of ACT I, which included 1,453 asymptomatic patients enrolled at 62 US sites from 2005 to 2013 after stopping short of the planned goal of 1,658 patients due to slow accrual. The patients, who were all younger than 80 years and had standard surgical risk, were randomized 3:1 to stenting with the Xact stent and an Emboshield, Emboshield Pro, or Emboshield NAV6 protection device (all Abbott Vascular) or to endarterectomy.

The primary endpoint was the rate of stroke, death, or MI within 30 days of the procedure and ipsilateral stroke from 31 days to 1 year. The rate was 3.8% with stenting and 3.4% with surgery, a difference that met criteria for noninferiority (P = .01).

Within the first 30 days, there were no significant differences between groups in rates of various outcomes, although minor stroke was numerically higher after stenting (2.4% vs 1.1%; P = .20) and composite morbidity, which included cranial and peripheral nerve injury, vascular injury, noncerebral bleeding, wound complications related to neck incision or femoral puncture site, and other complications, was numerically higher after surgery (4.7% vs 2.8%; P = .13).

Follow-up out to 5 years did not reveal any disparity in outcomes between the 2 arms, either.

“Carotid stenting is a reasonable alternative to carotid endarterectomy for patients who have asymptomatic stenosis [and] who for whatever reason need or desire to undergo a revascularization procedure,” Wechsler said.

CREST

Thomas Brott, MD, of the Mayo Clinic (Jacksonville, FL), presented the 10-year results of the CREST trial, which randomized 2,502 patients with conventional surgical risk to stenting with the RX Acculink stent and, when possible, the RX Accunet embolic protection device (both Abbott Vascular) or to endarterectomy at 117 centers in the United States and Canada. The trial included both asymptomatic and symptomatic patients.

Previously presented results with follow-up to 4 years showed that there was no difference in the rate of stroke, MI, or death within 30 days or subsequent ipsilateral stroke between the 2 trial arms. But because the average life expectancy for Medicare patients is 20 years for women and 18 for men, the researchers wanted to examine longer-term outcomes. Overall, 1,607 patients consented to long-term follow-up.

The primary endpoint for long-term follow-up was ipsilateral stroke after the periprocedural period. That occurred in 6.9% of stented patients and 5.6% of patients who underwent endarterectomy (HR 0.99; 95% CI 0.64-1.52). The findings were similar in both asymptomatic and symptomatic patients.

Looking at the primary composite endpoint of periprocedural events plus subsequent ipsilateral stroke, there was still no difference between the stenting and surgery groups (11.8% vs 9.9%; HR 1.10; 95% CI 0.83-1.44), with consistent results across subgroups defined by age, sex, symptom status, and severity of stenosis.

Only for the composite endpoint of periprocedural stroke and death plus subsequent ipsilateral stroke was there a discrepancy between the trial arms. That outcome was more frequent after stenting (11.0% vs 7.9%; HR 1.37; 95% CI 1.01-1.86), with much of the difference emerging shortly after the procedures.

There was no difference over the long-term in the rate of restenosis or revascularization (12.2% vs 9.7%; HR 1.24; 95% CI 0.91-1.70).

Choice Comes Down to Shared Decision Making

Rosenfield told TCTMD that the ACT I results show that carotid stenting is durable and that the trial “should ultimately impact reimbursement and selection for patients.”

Although there are patients who would benefit more from endarterectomy and others who would fare better with stenting, there is a large group of patients who would benefit equally from either intervention, Rosenfield said.

“What this trial confirms is that it is completely reasonable and appropriate to offer those patients who would benefit from either one a choice and make a shared decision about what the best treatment is for them,” he said. “The hope is that this enables this therapy to be more available and accessible to patients because they deserve to have this treatment available, as they have surgical revascularization.”

Mark Alberts, MD, of the University of Texas Southwestern Medical Center (Dallas, TX), said ACT I and CREST together “show the durability of both endarterectomy and stenting [and] that they’re both now major players in terms of our treatment armamentarium for patients with symptomatic or asymptomatic carotid stenosis. So this is good because… it gives us different options to offer our patients and it sort of opens the door to have an informed discussion.”

Factors that might come into play when choosing one or the other include local expertise—whether a certain area has more skilled surgeons or more skilled interventionalists—and cardiac risk, according Ralph Sacco, MD, of the University of Miami (Miami, FL).

For example, if patients have high cardiac risk, said Sacco, who is a past president of the American Heart Association, they might do better with stenting because the trials have shown that MI risk is higher with endarterectomy.

Wechsler said that patients might shy away from surgery if they do not want general anesthesia or a scar on their neck or simply do not want to undergo a surgical procedure. On the other hand, he said, stenting is a newer procedure that involves disturbing the plaque in the carotid artery and potentially sending fragments into the brain.

Wait for CREST-2

In an editorial accompanying the NEJM papers, J. David Spence, MD, of Western University (London, Canada), and A. Ross Naylor, MD, of Leicester Royal Infirmary (Leicester, England), acknowledge that the issue about the durability of stenting “has now surely been resolved.”

But there remain questions surrounding the generalizability of trial findings to routine clinical practice, about the need for any carotid artery interventions in asymptomatic patients, and about the relevance of trial findings in the context of contemporary medical therapy, they say.

“Pending the completion of CREST-2, we think that it would be desirable for interventionists and surgeons to forgo stenting and endarterectomy in low-risk asymptomatic patients outside the trial,” they argue. “This restraint would not only spare patients from procedures that may be unnecessary, but it should also facilitate early completion of the trial… so that it may be possible to identify which patients will benefit from an intervention rather than medical therapy alone in an evidence-based rather than an eminence-based manner.”