ACT I

Published

Rosenfield K, et al. "Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis". The New England Journal of Medicine. 2016. 374(11):1011-20.
PubMed • Full text • PDF

Clinical Question

In patients with asymptomatic severe carotid stenosis (70-99%) at average risk for surgical complications, is carotid artery stenting with embolic protection noninferior to carotid entarterectomy with regard to death, stroke, or MI?

Bottom Line

In patients with asympatomatic severe carotid stenosis (70-99%) at average risk for surgical complications, carotid artery stenting with embolic protection was noninferior to carotid endarterectomy. Specifically, there was no difference in death, stroke, or MI at 30 days and ipsilateral stroke at 1 year. Extended follow up for 5 years showed similar rates of overall survival and stroke. Carotid artery stenting with embolic protection appears to be a reasonable alternative to endarterectomy in this population.

Major Points

Extracranial carotid artery disease is thought to be responsible for up to 20% of all strokes. Based on the strength of major RCTs including NASCET and ESCT, patients with symptomatic carotid artery stenosis (stroke or TIA) greater than 50% are routinely revascularized in order to reduce risk of subsequent stroke. A large meta-analysis of several RCTs comparing surgical endarterectomy (CEA) vs. carotid stenting in this population suggests higher perioperative stroke or death rates with stenting As a result, carotid stenting in this population is generally reserved for patients at high or unacceptable surgical risk.

The data are less clear regarding the optimal management of patients with asymptomatic severe carotid artery stenosis, the population in which the majority of revascularization procedures are performed. The ACAS and ASCT trials showed that among asymptomatic patients with carotid artery stenosis greater than 60%, the risk of stroke or death was lower when immediate endarterectomy was performed. The CREST trial suggested that endarterectomy and stenting with embolic protection provided similar outcomes in this population with perhaps higher complication rates with stenting in patients above age 70. However, this study was limited by including both symptomatic and asymptomatic patients and was not powered to detect outcome differences in the asymptomatic population.

The 2016 Asymptomatic Carotid Trial (ACT) I randomized 1453 patients with asymptomatic severe carotid stenosis (70-99%) not at high surgical risk to carotid stenting with embolic protection versus carotid endarterectomy. ACT I demonstrated that stenting was noninferior to endarterectomy with regard to a primary outcome of death, stroke, or MI at 30 days and ipsilateral stroke at 1 year. Notably, there was a 1.4% absolute risk increase in stroke at 30 days with stenting vs. endarterectomy although this was not statistically significant. At 5 years of follow up, stenting remained noninferior to endarterectomy with regard to both overall and stroke-free survival. The cumulative rate of stroke-free survival was 93.1% with stenting versus 94.7% with endarterectomy. Procedural complications were similar in both groups with a 1% absolute higher risk in cranial nerve injury with endarterectomy. These data suggest that carotid stenting with embolic protection is a reasonable alternative to carotid endarterectomy in patients with asymptomatic severe carotid stenosis at standard surgical risk.

Guidelines

No guidelines have been published reflecting the results of this study.

Design

• Multicenter, randomized, controlled trial
• N=1453
  • Carotid stenting (n=1,089)
  • Carotid endarterectomy (n=364)
• Setting: 65 sites in the US
• Period: March 30, 2005 - January 18, 2013
• Duration follow-up: 5 years
• Analysis: Intention-to-treat
• Primary outcomes: Death, stroke, nonfatal MI 30 days after procedure and ipsilateral stroke 1 year after procedure

Population

Inclusion Criteria

• Deemed a candidate for either CEA or carotid stenting per referring physician
• Age 79 or younger
• Bifurcation carotid stenosis 70-99%
• Asymptomatic carotid artery stenosis (no TIA, CVA, or amaurosis fugax within preceding 180 days)

Exclusion Criteria

• High surgical risk
• Substantial contralateral carotid stenosis (>60%)

Baseline Characteristics

From the stenting group.

• Demographics: Mean age 68 years, 61% male, 90% white
• Co-morbidities: HTN 91%, HLD 90%, past smoker 74%, current smoker 24%, DM 36%, CAD 53%, LV dysfxn 8%, PAD 36%, contralateral carotid disease 41%, CVA 7%, TIA 6%, COPD 12%, CKD 8%
• Lesion characteristics: Mean stenosis 74%, mean length 19mm, ulcerated 16%, thrombus 0.9%

Interventions

• All patients deemed to be candidates for either CEA or carotid stenting
• Patients randomized 3:1 to undergo stenting with embolic protection or carotid endarterectomy
  • For stenting, closed-cell, nitinol stents with a tapering diameter (Xact) were used in conjunction with distal embolic protection
• Before enrollment, a study neurologist or neurosurgeon verified asymptomatic status (free from stroke, TIA, or amaurosis fugax) 180 days from enrollment
• All patients treated with 325MG aspirin daily starting three days prior to procedure and indefinitely thereafter
• Patients who underwent stenting also received clopidogrel daily for 3 days prior to procedure and 3 months thereafter
• Neurologic assessment on day 1, months 1, 6, and 12, and every year thereafter until year 5
  • Study group assignment not blinded at these assessments (patients had neck scars with CEA)

Outcomes

Comparisons are stenting vs. CEA.

Primary Outcomes

Death, stroke, or MI (30 days) and ipsilateral stroke (365 days)

3.3% vs. 3.4% (95% CI upper limit 2.27; P=0.01 for noninferiority)

Secondary Outcomes

Death (30 days)

0.1% vs. 0.3% (P=0.43)

Stroke(30 days)

2.8% vs. 1.4% (P=0.23)

MI(30 days)

0.5% vs. 0.9% (P=0.41)

Freedom from clinically-driven target-vessel revascularization (1 year)

99.4% vs. 97.4% (P=0.005)

Overall survival (5 years)

87.1% vs. 89.4% (P=0.21)

Freedom from all stroke (5 years)

93.1% vs. 94.7% (P=0.44)

Adverse Events

Composite Complications (30 days)

2.8% vs. 4.7% (P=0.13)

Cranial Nerve Injury (30 days)

0.1% vs. 1.1% (P=0.02)

CEA incision or puncture site bleeding (30 days)

0.3% vs. 1.1% (P=0.07)

Criticisms

• Study stopped early due to slow enrollment, limiting potential power to detect an outcome difference between carotid stenting and CEA, although enrollment did reach 88% of target with 75% revised power.
• Significance of numerically higher 30 day stroke rate with stenting (1.4% absolute risk increase) unclear, particularly given concerns regarding underpowering.
• No medical therapy arm to assess benefit of any revascularization versus medical care only.
• No blinding at point of outcome assessment, allowing for potential outcome adjudication bias.

Funding

• Study funded by Abbott Vascular
• First author reports receiving advisory fees from study sponsor