Carotid Endarterectomy vs Stenting: When Randomized Becomes a Dirty Word

Abstracts & Commentary

Synopsis: Among patients with severe carotid-artery stenosis and coexisting conditions, carotid stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy.

Source: Yadav JS, et al. The SAPPHIRE Investigators. Protected Carotid Artery Stenting vs Endarterectomy in High-Risk Patients. N Engl J Med. 2004;351:1493.

Carotid endarterectomy (CEA) is the standard of care for patients with symptomatic carotid stenosis of > 70% severity. In men, CEA may be considered for stenoses as mild as 50-69%. For asymptomatic patients with stenoses > 60%, CEA may also be advisable, but the benefits are less robust. It is on this backdrop, that an alternative therapy, carotid artery stenting (CAS) with distal embolic protection, enters into the clinical calculus. Very recently, on August 31, 2004, the first stent system for the carotid (Guidant Corp.) passed through FDA approval.

The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial compared CAS with CEA in a group of patients with comorbid conditions putting them in a high-risk category. In fact, these patients would have been excluded from prior randomized studies comparing efficacy of CEA with best medical management. Many of these patients had clinically significant cardiac disease, contralateral carotid occlusion, or had restenosis following prior CEA. Of a total of 747 patients entered into the study, 413 were determined to be non-randomizable, and were treated with CEA or CAS at the discretion of their treating physicians. The vast majority of these (406) were determined to be poor surgical candidates, and underwent CAS. The randomized cohort was therefore quite small, comprising the remaining 334 patients. These were equally divided between CEA and CAS. The goal of the trial was not to show that CAS was superior to CEA, but rather clinical equivalence or non-inferiority.

The primary end point was stroke, myocardial infarction, or death within 30 days, or stroke/death up to 1 year. There were 20 events in the CAS patients and 32 in the CEA group, a non-significant trend in favor of CAS. This finding established non-inferiority of CAS, when compared to CEA. With the inclusion of myocardial infarction up to 1 year (a secondary end point), the advantage of CAS reached statistical significance (12% for CAS vs 20% for CEA, P 0=.048). Peri-procedural complications, including stroke, within 30 days, were 4.4% among CAS patients and 9.9% among CEA patients (P = .09). The complication rate for CAS for these high-risk patients compares favorably to that of CEA in low-risk patients (3-6%).

Unfortunately, the SAPPHIRE study was terminated early when recruitment of patients slowed in the face of competition from non-randomized CAS registries. Had the study been taken to completion, the study may have been powered to show superiority of CAS over CEA, rather than merely non-inferiority.

Commentary

Although controversial and only partially randomized, the SAPPHIRE study is the only existing direct comparison between CAS and CEA. In the aftermath of SAPPHIRE, a series of industry-sponsored trials, bearing catchy acronyms such as CABERNET, MAVERIC, and SECURITY, have focused on CAS alone, to the exclusion of CEA. With these studies, merely collections of cases rather than true science, CAS technology has continued to push ahead of the less sexy CEA procedure. Only the publicly funded CREST study (Carotid Revascularization Endarterectomy vs Stenting Trial), along with a similar European trial will offer an unbiased, randomized head-to-head comparison. Unfortunately, such trials can be a hard sell to patients, especially now that stents are FDA approved and readily available to patients and physicians outside the confines of research studies. In addition, CAS is a moving target. Today’s stents are superior to those of yesterday, and the more advanced stents to come (eg, those eluting anti-fibrotic drugs) will not bear comparison to those of today. Surgical technique remains essentially static, while endovascular technology is ever changing. Coronary artery stents are dramatically reducing the indications for coronary artery bypass grafting. Similarly, for carotid artery stenting, the future is now, with or without randomized trials. —Alan Z. Segal

Alan Z. Segal, MD Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital is Assistant Editor of Neurology Alert.