Data raise questions about expanded availability of CAS

The question of whether carotid artery stenting should be available for all patients boils down to the data, which can be cast in different lights, speakers said at the International Symposium on Endovascular Therapy.

Two experts — William A. Gray, MD, system chief of the division of cardiovascular disease at Main Line Health and president of the Lankenau Heart Institute in Wynnewood, Pennsylvania, and Anthony J. Comerota, MD, FACS, FACC, medical director of the Eastern Region of the Inova Heart and Vascular Institute and Inova Alexandria Hospital in Virginia — went head to head on this topic during a debate at ISET.

All studies were under scrutiny, but the CREST trial took center stage, with each expert providing his take on the data.

Increased uptake

Gray noted that it is reasonable to ponder whether CAS or endarterectomy is best for patients, as endarterectomy outcomes, particularly in terms of stroke and death, have improved significantly during the last 40 years.

“It is without a doubt the gold standard. It is an elegant, effective operation, and I send more patients today for it than I ever have before because I know there are certain patients for whom stenting is not appropriate,” Gray, who was tasked with arguing in favor of CAS, said during his presentation. “However, we can’t lose sight of the fact that over the last decade — not 40 years — carotid stenting started with risks for stroke and death that were around 8% and are now down to 1% to 1.5%. This occurred in a miraculously short period of time, and current considerations should recognize the more recent, state-of-the-art outcomes, and not reference the 'pioneer' days.”

The positive FDA approval trials, which focused on high-risk patients, demonstrated the noninferiority or near-superiority of CAS compared with endarterectomy. Subsequently, around 2005, after FDA and CMS approval, the volume of CAS significantly increased, leading to a significant reduction in overall complication rates, according to Gray.

Four trials — EVA-3S, SPACE, ICSS and CREST — then provided insight into the use of CAS in standard-risk symptomatic patients. The first three trials, however, suggested that these patients fared worse with CAS, but they had several issues, including that operator experience was inadequate and embolic protection was absent or underutilized, he noted.

Supporting evidence

The CREST trial, which was published in The New England Journal of Medicine in 2010, showed no difference between CAS and endarterectomy in freedom from the primary endpoint (stroke, MI or death during the periprocedural period and ipsilateral stroke within 4 years), freedom from all-cause mortality at 4 years, freedom from ipsilateral stroke from 31 days to 4 years and freedom from target lesion revascularization at 4 years, according to Gray.

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“Where there were differences — minor stroke and MI — we see that minor stroke didn’t lead to any residual deficit in the vast majority of patients, but MI actually had a strong association with death at 4 years,” he said. “So, the difference between stenting and surgery was really between minor stroke and MI, and MI had a mortality outcome, confirming the previously known impact of MI after major vascular procedures.”

Gray also highlighted the lower rates of access-site complications and cranial nerve injury with CAS vs. endarterectomy. Patient satisfaction was also better at 2 weeks and 1 month with CAS, but they were similar for CAS and endarterectomy at 1 year, which was not surprising given the surgical access point, according to Gray.

There were also no differences between the two procedures in terms of cost at the time of index hospitalization or out to 1 year, he added.

“In my mind, CREST really answers the question of whether CAS should be available to all patients,” Gray said. “In the final reckoning, endarterectomy and stenting have similar primary outcomes, so why are we even having this conversation? We are because, although the FDA approved all of these procedures in all patients, CMS has only approved CAS in high-surgical-risk patients, which, based on the data, seems silly.”

Questions still remain and investigation is ongoing, Gray noted, but this should not impede the availability of CAS.

“Should CAS or endarterectomy be done on every patient? No. Should it be available to everybody? Yes,” he said.

A different take

In his rebuttal, Comerota noted that a more complete picture of the CREST trial, which he agreed is one of the most rigorous trials in this field, is necessary before drawing firm conclusions.

Nonfatal MI, for instance, is an inappropriate primary endpoint when discussing CAS and endarterectomy, which are procedures designed to reduce the future risk for stroke. MI is included because of the concern for subsequent mortality in patients with MI, he said, but stroke and death are of greater relevance.

For example, Comerota noted that in CREST, one patient in approximately 2,500 died from a procedure-related MI, whereas 13 died from a procedure-related stroke within 30 days.

“Clearly, that’s a window into what is important,” he said. “By no means am I minimizing the importance of MI, but what you see is an increased risk for MI in carotid endarterectomy patients, which led to equivalence in the primary endpoint. However, if we did not have MI as a primary endpoint, stroke and death were significantly lower in patients who were randomized to carotid endarterectomy, whereas we see that only death from MI occurred within 30 days.”

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The same observations were seen out to 4 years, which Gray emphasized during his presentation, he added.

Further, Comerota noted, although only one patient died from a procedure-related MI at 30 days, six patients with nonfatal procedure-related MIs in the CAS group and seven with nonfatal procedure-related MIs died in the endarterectomy group, making for a difference of only one patient, at 4 years.

Important subanalyses

Comerota also questioned whether outcomes of CAS and endarterectomy may differ based on other factors, such as symptomatic status, sex and age. Again, he highlighted data from the CREST trial.

In CREST, there was a significant increase in stroke and death in the CAS group vs. the endarterectomy group in both symptomatic and asymptomatic patients, according to Comerota, and in terms of the primary endpoint, women appeared to benefit more from endarterectomy than CAS.

“If we get down into the nitty gritty and integrate procedure-related events in women and men and whether they were symptomatic or asymptomatic, symptomatic women offered CAS had a 9.2% primary endpoint compared with 4% in the endarterectomy group. That’s impressive,” he said. “Men did reach the primary endpoint in favor of CAS vs. endarterectomy, and when you see the stroke and death rate, it’s significantly higher for women.”

A trend toward similar observations, although not significant, was observed in asymptomatic patients, Comerota noted.

Age is also a determinant of outcome, he added. Young patients were served better with CAS, whereas those older than 64 years had better outcomes with endarterectomy. Similarly, patients with sequentially remote and long lesions fared better with endarterectomy. There were also differences in surgical outcome whether the CEA arteriotomy was closed with a patch or not. Those patients undergoing CEA who were not patched had an increased risk for stroke and restenosis. Notably, in the no-patch group, the procedures were predominantly performed by neurosurgeons. The majority of vascular surgeons closed the arteriotomy with a patch.

“One could argue that the primary endpoint would have been reached if vascular surgeons performed the CEAs in CREST compared with the inclusion of neurosurgeons, who generally do not have familiarity in handling atherosclerotic blood vessels,” he said.

“Based upon the best available data, CAS should only be available for symptomatic men younger than 70 years with a single short carotid lesion.” – by Melissa Foster

References:

Gray WA. Carotid stenting should be available for all patients now: pro.

Comerota AJ. Carotid stenting should be available for all patients now: con. Both presented at: the International Symposium on Endovascular Therapy (ISET); Jan. 27-30, 2019; Hollywood, Fla.

Disclosures: Gray reports he is a consultant for Abbott Vascular, Boston Scientific, Cook Medical, Medtronic, Shockwave, W.L. Gore; he is a major stockholder in Biocardia, Contego Medical, Silk Road; and he has contracted research with Abbott Vascular, Boston Scientific, Intact Vascular, Shockwave and W.L. Gore. Comerota reports he is a consultant for the NIH ATTRACT Trial; he has received grant or research support for the NIH ATTRACT Trial and Cook-VIVO Trial; and he has received NIH funds as a CREST Trial site principal investigator.