Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy: 3-Year Results - SAPPHIRE: 3-Year Results

Description:

The goal of the trial was to compare carotid stenting with an embolic protection device versus carotid endarterectomy (CEA) in patients with severe symptomatic or asymptomatic carotid artery stenosis and increased surgical risk.

Hypothesis:

The rate of the composite endpoint of death, myocardial infarction (MI), or stroke within 30 days plus ipsilateral stroke or death between 31 days to 3 years will be similar between the stent arm and the CEA arm.

Study Design

  • Randomized
  • Stratified

Patients Screened: 747
Patients Enrolled: 334
Mean Follow Up: 3 years
Mean Patient Age: 72
Female: 33

Patient Populations:

Stenosis of at least 50% in symptomatic patients or at least 80% in asymptomatic patients and at least one high surgical risk criterion

High surgical risk defined as:
  • Age greater than 80 years
  • Congestive heart failure
  • Abnormal stress test
  • Need for open heart surgery
  • Severe pulmonary artery disease
  • Contralateral carotid occlusion
  • Contralateral laryngeal nerve palsy
  • Restenosis after CEA
  • Previous radical neck surgery or radiation therapy to the neck

Exclusions:

Ongoing stroke, total carotid artery occlusion, recent percutaneous or surgical intervention, or ostial lesion

Primary Endpoints:

Composite of death, stroke, or MI at 30 days plus death or ipsilateral stroke between 31 days to 1 year

Secondary Endpoints:

Composite of death, stroke, or MI at 30 days plus death or ipsilateral stroke between 31 days to 3 year

Drug/Procedures Used:

Patients with severe internal carotid artery stenosis and high surgical risk were randomized to stenting with embolic protection (n = 167) or CEA (n = 167). A team of an interventionalist, vascular surgeon, and neurologist determined if the patient was too high risk to be randomized in the trial, and was then entered in a registry.

Concomitant Medications:

All patients received aspirin and heparin during the procedure. Patients who received a stent were also treated with clopidogrel prior to and for 2-4 weeks after the procedure.

Principal Findings:

Complete follow-up was available in 85.6% of the stent group and 70.1% of the CEA group. The incidence of the prespecified secondary endpoint at 3 years was 24.6% for the stent group and 26.9% for the CEA group (p = 0.71). Among asymptomatic patients, this endpoint occurred in 21.4% versus 29.2% and among symptomatic patients, 32.0% versus 21.7%, respectively.

Cumulative mortality was 20.0% versus 24.2% (p = 0.68), respectively. Between 1 and 3 years, there were 19 additional deaths in the stent group and 14 additional deaths in the CEA group. The cause of death was cardiac in 49% of the stent group and 43% of the CEA group.

Cumulative stroke was 10.1% versus 10.7% (p = 0.77), respectively. In the stent group, 26.7% of the strokes were contralateral versus 40% of the CEA group. Between 1 and 3 years, there were four additional ipsilateral strokes in the stent group and one additional stroke in the CEA group.

Cumulative target vessel revascularization was 3.0% versus 7.1% (p = 0.26), respectively, for stenting versus CEA.

Interpretation:

Among high surgical risk patients with a severe carotid artery stenosis, carotid artery stenting with embolic protection produces similar long-term results to CEA. Specifically, there is no difference in the composite outcome of death, stroke, or MI at 30 days plus death or ipsilateral stroke between 31 days to 3 years.

Mortality was high during follow-up, given the advanced age and comorbidities of the patient population. Approximately half of the deaths were due to cardiac causes. Strokes continued to accumulate at a similar rate in both groups, both late in follow-up and also in contralateral locations. Target vessel revascularization was infrequent in both groups.

The high loss-to-follow-up that occurred in both groups, but especially the CEA group is concerning, since it could have produced a source of bias. These findings do not apply to low to intermediate surgical risk patients with carotid artery stenosis. This patient population is currently being evaluated in the ongoing CREST trial.

References:

Gurm HS, Yadav JS, Fayad P, et al. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med 2008;358:1572-1579.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Interventions and Vascular Medicine

Keywords: Cause of Death, Registries, Myocardial Infarction, Stroke, Follow-Up Studies, Embolic Protection Devices, Endarterectomy, Carotid, Comorbidity, Carotid Arteries, Carotid Stenosis, Stents


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