Treatment of Carotid Artery Stenosis: Surgery, Stenting, or a Statin?
Abstract & Commentary
By Matthew Fink, MD Vice Chairman, Professor of Clinical Neurology, Weill Medical College, Chief of Division of Stroke and Critical Care Neurology, NewYork-Presbyterian Hospital Dr. Fink reports no relationships relevant to this field of study.
Synopsis: In high-risk patients with significant carotid artery stenosis, carotid endarterectomy and carotid stenting appear equivalent both for efficacy and adverse events.
Source: Gurm HS, et al; SAPPHIRE Investigators. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med 2008;358:1572-1579.
As more information becomes available from randomized clinical trials, we are able to make more rational decisions regarding the treatment of patients with carotid artery stenosis. In the December 2006 Neurology Alert, Dr Stieg discussed the results of the French randomized trial1 of carotid endarterectomy (CEA) vs. carotid artery stenting (CAS) and noted that the 30-day risk and 6-month risk of stroke or death were higher in the CAS group (9.6% vs. 3.9% at 30 days; 11.7% vs. 6.1% at 6 months). The French study was terminated early by the Safety Monitoring Committee due to safety and futility issues. Dr. Stieg concluded that, based on that study, CEA was the preferred treatment unless the patient had a high surgical risk.
The current report cited above from the SAPPHIRE investigators has extended their earlier report2 to provide us with 3-year follow-up data on 260/334 patients who were originally randomized to carotid endarterectomy or carotid artery stenting with an emboli-protection device. These patients had symptomatic carotid artery stenosis >50%, or asymptomatic carotid stenosis > 80%, and were considered high-risk for surgery based on medical comorbidities, contralateral carotid occlusion, previous neck surgery or radiation, and age > 80 years. The SAPPHIRE report in 2004 showed that CAS was not inferior to CEA (p=0.004), and showed a trend of fewer cardiovascular events at 1 year (cumulative incidence=12.2% for CAS and 20.1% for CEA, but not significant for superiority). The current report shows that the primary end point at the end of 3 years (composite of death, stroke, or myocardial infarction) was not significantly different between the two groups: the stenting group had a cumulative incidence of 24.6% (Kaplan-Meier estimate, 26.2%), while the endarterectomy group had a cumulative incidence of 26.9% (Kaplan-Meier estimate, 30.3%). Of note, most of the major adverse events between 1 and 3 years was due to deaths, the majority of which were from non-neurological causes. Death rates were approximately 7-8% per year. All patients were treated with aspirin and clopidogrel for 2-3 weeks after stent placement, but there is no further information about other medical therapies during the follow-up period.
Commentary
SAPPHIRE is the first well-designed trial to report the long-term results of CEA vs. CAS for both symptomatic and asymptomatic carotid artery stenosis in high-risk patients. The results show no significant differences in outcome between the two procedures. Can we extrapolate these data to the usual, low- or moderate-risk patient with carotid stenosis? I don't believe so, and we will need to wait for the results of a large trial3 designed to answer that question before we have a definitive answer.
But, what role does medical therapy play? In the earlier trials comparing CEA to "best medical therapy" in both symptomatic and asymptomatic patients, aspirin was the only defined medical therapy, and statins were only introduced in the 1990s.4,5 Yet, most of the deaths that occur after CEA or stenting are from myocardial infarction and non-neurologic cardiovascular causes. Statins have been shown to have a profound effect in reducing death from cardiovascular causes, but they also have been shown to decrease the progression of carotid atherosclerosis and in many cases to cause reduction in carotid atherosclerosis. The recent study that looked at the benefits of simvastatin with or without ezetimide6 showed that in both groups with familial hypercholesterolemia treated with intensive lipid-lowering medications, regression in the mean carotid artery intima-media thickness was seen in 45% of all patients given simvastatin therapy over a 24-month period. In addition, new plaque formation was seen in only 2.8% of patients who were treated with simvastatin alone. There is no study that has compared current best medical therapy (antiplatelet, statin, antihypertensives, lifestyle modifications) with CEA or CAS and it is highly unlikely that such a study will ever be performed. Yet, the impact of these medical therapies, based on the cardiovascular literature, is likely to be profound and should be instituted in all at risk-patients, regardless of whether they are being considered for CEA or CAS.
References
1. Mas JL, et al. N Engl J Med 2006;355:1660-1671.
2. Yadav JS, et al. N Engl J Med 2004;351:1493-1501.
3. CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial). www.clinicaltrials.gov, number NCT00004732.
4. Sacco RL, et al. Stroke 2006;37:577-617.
5. Goldstein LB, et al. Stroke 2006;37:1583-1633.
6. Kastelein JJ, et al. N Engl J Med 2008;358:1431-1443.
In high-risk patients with significant carotid artery stenosis, carotid endarterectomy and carotid stenting appear equivalent both for efficacy and adverse events.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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