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Critical Issues and Controversies in Carotid Artery Stenosis

Many randomized controlled trials (RCTs) concerning carotid disease management are obsolete (or even flawed) by today’s standards. Nevertheless, current decision-making may be influenced by their results. In their comment on our article, Moris et al raise some issues that should be addressed in future RCTs. Some additional comments may be of interest. The recently published long-term results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) are an example of how opinion can be misled from (even unintentional) flaws in study design. The CREST was conducted in 117 centers in the United States and Canada. All CREST interventionalists had to undergo comprehensive training and credentialing in order to ensure low periprocedural event rates. The recruitment period for CREST was December 2000 to July 2008. At that time, the general belief was that a carotid intervention (endarterectomy [CEA] or stenting [CAS]) should not be offered early after a neurologic event. For this reason, the recommendation at that time was that a carotid intervention should be offered within 6 months of the index event. This was one of CREST’s inclusion criteria, that is, ‘‘patients were considered to be symptomatic if they had had a transient ischemic attack, amaurosis fugax or minor nondisabling stroke involving the study carotid artery within 180 days before randomization.’’ The recommendation that CEA/CAS should be performed within 2 weeks of the index event was added in the 2006 guidelines. By that time, it was realized that by prolonging the time to surgery, the risk of a recurrent event increases substantially (whereas the periprocedural stroke risk is reduced considerably). Obviously, when the CREST recruitment period began in 2000, the organizing committee was not aware of the 2006 recommendation. Consequently, many of the symptomatic patients recruited in CREST were offered CAS/CEA outside the current 2-week optimal threshold for intervention. Therefore, should results not obtained in accordance with current guidelines or by today’s standards influence decisions? Several other factors render the majority of the carotid RCTs obsolete, for example: 1. Best medical treatment (BMT): Earlier RCTs did not implement what is now considered as BMT. For example, in 2010, the Asymptomatic Carotid Surgery Trial published its 10-year results comparing CEA versus no intervention for patients with asymptomatic carotid. Use of lipid-lowering drugs was similar between the 2 groups, and this use increased from about 10% in 1993 to >80% in 2003. Despite that, the vast majority of patients receiving statins were prescribed simvastatin 10 mg/d, which reflects suboptimal treatment. Baseline statin use was not recorded in some studies (eg, the General Anaesthesia versus Local Anaesthesia trial). Any RCT not using current BMT is flawed as it does not reflect optimal current practice. 2. Specific center performance/experience with CAS/CEA: The strict credentialing process in CREST is likely to be one of the reasons why this RCT reported improved results for CAS compared with previous RCTs. In contrast, a recent systematic review of >1 500 000 CEA and CAS procedures showed that for asymptomatic patients, CAS was associated with in-hospital/30-day death/stroke rates that exceeded the 3% of American Heart Association (AHA)–recommended risk threshold in 9 (43%) of 21 registries; for symptomatic patients, CAS exceeded the 6% by the AHA-recommended risk threshold in 13 (72%) of 18 registries. Therefore, should RCTs guide clinical practice if they do not reflect reality?