Carotid Stenosis Procedures Equally Effective for Long-Term Prevention

By Crystal Phend
BOSTON, April 9, 2008-- High-risk patients with severe carotid artery stenosis may have equivalent long-term outcomes whether treated with stenting or conventional endarterectomy, researchers found.
The cumulative incidence of major adverse events through three years was 24.6% for stenting done with emboli protection compared with 26.9% for endarterectomy (P=0.71), reported Donald E. Cutlip, M.D., of Harvard, and colleagues, in the April 10 issue of the New England Journal of Medicine.
The incidence of stroke in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial was an identical 9% at three years whether patients had stenting or gold-standard open surgery.
Short-term safety results had likewise shown no difference between procedures, even though the EVA-3S trial had suggested an advantage for endarterectomy among symptomatic patients (See: Endarterectomy Safer than Carotid Stenting in Symptomatic Patients).
The SAPPHIRE findings represent the first look at longer-term efficacy in a randomized clinical trial, said co-author Hitinder S. Gurm, M.D., of the University of Michigan in Ann Arbor, in an interview.
Physicians can now choose between procedures for these patients based on individual anatomy and medical problems, he said, "knowing that whatever procedure the patient gets, the long-term outcome would be fairly similar."
Patients in the SAPPHIRE study had symptomatic carotid stenosis of more than 50% of the luminal diameter or asymptomatic stenosis of more than 80%.
All were at high surgical risk based on clinically significant cardiac disease, severe pulmonary disease, contralateral carotid occlusion, contralateral laryngeal-nerve palsy, recurrent stenosis, previous radical surgery or radiation therapy to the neck, or an age of more than 80 years.
The trial originally included 334 patients randomized to stenting with an emboli-protection device or carotid endarterectomy. At three years, 143 stenting group patients and 117 surgery group patients had clinical follow-up data available.
The primary endpoint of major adverse events through one year showed no difference between the groups.
Likewise for long-term outcomes, the major secondary endpoint of death and ischemic events through 30 days and death and stroke through three years showed only a nonsignificant 2.3% lower incidence for stenting versus surgery (95% CI -11.8 to 7.0).
Most of the events that occurred from one to three years of follow-up were deaths, and the majority of those were from non-neurological causes. None of the event rates differed between groups.
The cumulative incidence rates through three years for stenting versus endarterectomy included:
18.6% versus 21% for all-cause mortality (P=0.68).
2.2% versus 2.9% for neurological-related deaths (P=0.99), of which two deaths in the stenting group and three in the endarterectomy group occurred beyond one year.
9% for stroke in both groups (P=0.99).
5.4% versus 8.4% for MI (P=0.39).
2.4% versus 5.4% for target vessel revascularization (P=0.71).
These findings apply only to high surgical risk patients, the researchers cautioned.
"On the basis of the similar long-term outcomes among high-risk patients in the two treatment groups, it may be tempting to infer that endarterectomy is preferable for lower-risk patients," they said.
But physicians need to await the results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), which included low- and moderate-risk patients, Dr. Gurm said.
It's also important to note, he said, that some patients might not have benefited from either invasive procedure because the death rate was high over three years, he said. A medical therapy arm was not included in this study.
Although the study included only patients referred for an intervention other than medical therapy, the researchers suggested that "invasive treatment for prevention of stroke is reasonable, even in a high-risk population, if the projected five-year mortality is less than 50% and the intervention is not itself associated with an increased risk of death or other major adverse effects related to safety."
The study was sponsored by Cordis. Dr. Gurm reported being named as an inventor on patents related to carotid artery stenting. A co-author reported being the inventor of the Angioguard emboli-protection device used in the SAPPHIRE trial, being a shareholder in Angioguard at the time of its purchase by Johnson & Johnson in 1999, and receiving recurring payments from Johnson & Johnson as a former shareholder of Angioguard. Other authors reported conflicts of interest for Cordis, Boston Scientific, Abbott Vascular Devices, Johnson & Johnson, Cook, ev3, and Lumen Medical. Two authors were employees of Cordis (a Johnson & Johnson company) and reported owning equity interest and holding stock options in Johnson & Johnson.
Primary source: New England Journal of MedicineSource reference:Gurm HS, et al "Long-term results of carotid stenting versus endarterectomy in high-risk patients" N Engl J Med 2008; 358: 1572-9.