Carotid Revascularization Endarterectomy vs. Stenting Trial: Long Term Follow-up

DESCRIPTION (provided by applicant): This is a competitive renewal for the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) that is designed to establish the relative efficacy of carotid endarterectomy (CEA) versus carotid artery stenting (CAS). During the initial funding period we have successfully completed enrollment of our pre-specified cohort of 2522 participants. Peri-procedural and mid-term outcomes, over a projected mean follow-up of 2.8 years, will be reported in February of 2010 or earlier. The primary results from CREST, publication of the primary results from ICSS, and the results of other revascularization trials including SAPPHIRE, EVA-3S, and SPACE will provide solid Level 1A evidence to guide carotid treatment over a 2 to 4 year time horizon. This is in contrast to patients living decades after CEA and CAS have been performed. The discordance between the time horizons of studies and the duration that patients may benefit creates a knowledge gap where there is a true dearth of evidence. In this competitive renewal we seek funding to continue to monitor these participants for an additional 5 years, with the potential for follow-up of up to 10 years. Our Primary Aim is to extend follow-up of the CREST cohort beyond 4 years and to assess the relative efficacy of CEA versus CAS over the 6 to 10 year post-procedural period in the prevention of ipsilateral stroke. Secondary aims will 1) assess if there are effect modifiers of the long-term durability of the two procedures, such as age, sex, pre-operative degree of stenosis and symptomatic status, 2) assess if there is a temporal change or pattern in the relative efficacy of the two procedures, 3) assess differences between groups in the rates of restenosis or revascularization, 4) link Medicare-eligible CREST participants with inpatient and outpatient CMS data files to assess patient outcomes and utilization of healthcare services, 5) collect DNA on available randomized subjects for future studies of genetic determinants of response to revascularization. We plan to extend follow-up of the existing 2522 enrolled with annual clinic visits interspersed with midpoint telephone contacts, from an average 2.8 years at the time of primary outcome reporting to an average 7.5 years, with a maximum follow-up of 10 years. With extended follow-up, statistical analysis of the primary aim will assess post-procedural treatment differences from Day 31 for up to 10 years of follow-up and is designed to provide 90% power to detect a hazard ratio of 1.67. With the focus of long-term follow-up on clinical outcomes, simplification of the follow-up protocol will result in reduced patient/clinic burden, reduced cost, and improved data quality. It is anticipated that CREST long-term results will have practice-changing implications regarding the standard of care for managing symptomatic and asymptomatic carotid arterial stenosis.