Richard Green, MD, discusses how these trial data have caused the endovascular community to debate the safety of CAS and proper trial design–and how that is a good thing.
Endovascular Today: Were the training requirements of SAPPHIRE more rigorous than EVA-3S? If so, why?
Dr. Green: The SAPPHIRE investigators, while early in their experience, were still more experienced than the majority of the EVA-3S group. The sponsors determine the training requirements for CAS studies in the US. The FDA signs off on that protocol. The current status in the US is that of perhaps 20 to 30 trial sites with extensive experience and everyone else. Although the CAPTURE data indicate no difference in outcome based upon operator experience, I find it hard to believe that a handful of cases are equivalent to hundreds of cases. I do not believe that either SAPPHIRE or EVA-3S demonstrated real-world use of CAS.
Endovascular Today: In the CEA arm of the study, EVA-3S reported one of the lowest rates of adverse events ever recorded. Do you have any thoughts on why its adverse event rate was so low?
Dr. Green: Carotid surgery is getting safer. This is a procedure that can be done under regional anesthesia and has the advantage of distal control of the ICA before any manipulation of a potentially unstable plaque. I think the MAE rate for CEA reported in EVA-3S is real world, and it is corroborated by similar results looking at administrative databases in the states of California and Maryland.
Endovascular Today: What is the overall significance of EVA-3S?
Dr. Green: Data from several sources now indicate that outcomes after CAS are related to a number of factors that are different than the factors influencing outcomes after CEA. The results of EVA-3S, if confirmed, would suggest that the symptomatic patient is at higher risk for CAS. These data in no way prove that, but they should raise our suspicion and prompt further investigation. I would hope that future studies require operators past their learning curves and utilize the best technology available. In other words, let us test the hypothesis by using high-volume operators and give them the option of a variety of protection systems and stent designs to optimize the result in each patient.
Endovascular Today: What can the EVA-3S and SPACE trials teach us?
Dr. Green: Trials designed poorly, even if prospective and randomized, do not provide definitive answers to difficult questions.
Endovascular Today: What are your thoughts on the decision to publish these data by Lancet and the New England Journal of Medicine?
Dr. Green: Both studies have certainly generated lots of discussion, and that is good as long as we insist on corroborating data before changing practice patterns.
Endovascular Today: Why was the CEA MAE rate so high in SAPPHIRE? How does that MAE rate compare to other studies of CEA?
Dr. Green: SAPPHIRE was the first CEA trial to look at and include MI as a primary endpoint. We have to remember that these patients were at extremely high risk for operation largely because of cardiac disease. I do not believe that the high MAE rates were a reflection of the surgeons, as many of them participated in ACAS (Asymptomatic Carotid Artery Stenosis) and had superb outcomes.
Endovascular Today: Why were the CEA results better in EVA-3S (MAE: 3.9%) than in SAPPHIRE (MAE: 12.6%)?
Dr. Green: The patients in EVA-3S and SAPPHIRE differed in the degree of operative risk. The former was a low-risk trial, the latter a high-risk trial. EVA-3S attempted to be a real-world trial and failed because of the lack of expertise in the CAS group. SAPPHIRE was never intended to be a real-world trial; it was conceived to show noninferiority of a new technique in a population known to be at extremely high risk for the conventional therapy.
Richard Green, MD, is Chairman, Department of Surgery at Lenox Hill Hospital in New York. Dr. Green may be reached at (212) 434-3400; firstname.lastname@example.org.