A Review of Current Carotid Artery Stent Trials
CAS for high-surgical-risk patients will most likely be approved in the coming year.
In the US there are multiple carotid artery stent trials and registries underway; one trial has recently been completed. Two randomized, controlled trials that are currently in progress are the SAPPHIRE trial and the CREST trial. In addition, there are several registries including ARCHeR, SHELTER/BEACH, MAVERICK, CABERNET, SECURITY, and CARESS.
The SAPPHIRE trial, the first carotid artery stent trial to be conducted in the US, was a randomized, controlled trial comparing carotid artery stenting (CAS) with emboli protection to carotid endarterectomy (CEA) in patients at high surgical risk. This trial was sponsored by Cordis Corporation, a Johnson & Johnson Company, (Miami, FL) utilizing the Cordis PRECISE nitinol carotid artery stent and the AngioGuard emboli prevention device (Figure 1). If there was a consensus of the neurologist, surgeon, and interventionalist, the patient was randomized to undergo either surgery or stenting. If the surgeon declined and the interventionalist agreed, then the patient was entered into the stent registry. If the interventionalist refused and the surgeon agreed, then the patient was entered in the surgical registry. Only centers with experienced interventionalists and surgeons were allowed into the study, and the Executive Committee reviewed the last 50 cases of the operators. The enrollment criteria required a stenosis of &Mac179;70% (measured by ultrasound) in symptomatic patients and &Mac179;80% in asymptomatic patients. Patients had to have one or more comorbid conditions that increased their surgical risk. The primary endpoints were death, stroke, and/or MI at 30 days postprocedure, and major adverse clinical advance plus death and/or ipsilateral stroke at 31 days to 12 months postprocedure. A quality of life and economic analysis are also being performed.
The SAPPHIRE study was designed to enroll at least 400 patients in the stent registry arm and up to 600 patents in the randomized arm. This study was stopped at the discretion of the sponsor after 723 patients were enrolled, and it posed several challenges. Many investigators had already reached their own conclusions regarding the benefit of CAS in these high-risk patients and had difficulty randomizing. In addition, many surgeons were reluctant to operate on these patients. This study was important, as it will finally provide information regarding CEA complication rates in a large group of patients that have been previously excluded from CEA studies. The SAPPHIRE study will also indicate which patients are truly inoperable, and it will also reveal whether CAS is superior to CEA in high-surgical-risk patients. The initial data will be presented at the American Heart Association meeting in November, and 1-year data will be available early next year.
The other major randomized study is the CREST study, which is jointly sponsored by Guidant Corporation (Indianapolis, IN) and the NIH. It randomizes symptomatic but low-surgical-risk patients to either CAS or CEA. The entry criteria are similar to the NASCET study. This study utilizes the Guidant AccuLink stent as well as the AccuNet emboli prevention device and it is expected to enroll 2,500 patients. The trial was started this year and should be completed within 5 to 7 years.
There are numerous carotid artery stent registries underway. The high-risk registries have many features in common. They have high-surgical-risk criteria similar to the SAPPHIRE trial. They all use emboli prevention devices and typically include nitinol stents or stainless steel self-expanding stents. The sample size is generally 400 patients and the primary endpoint is stroke, MI, and death at 30 days and at 1 year.
This summary of the various trials indicates that the field of CAS research is very active and dynamic. It has been helped substantially by the decision of the Health Care Financing Administration to provide reimbursement for CAS trials performed under an FDA IDE. It is expected that CAS for high-surgical-risk patients will be approved late next year on the basis of the SAPPHIRE 1-year results. n
Jay Yadav, MD, is Director of Vascular Carotid Intervention in the Department of Cardiology at the Cleveland Clinic Foundation in Cleveland, Ohio. Dr. Yadav may be reached at (216) 444-6160; firstname.lastname@example.org.