Carotid artery revascularization has shown better outcomes for carotid artery disease management when compared to medical therapy alone, particularly for symptomatic patients. However, we still debate whether revascularization is beneficial for asymptomatic patients in the setting of contemporary medical therapy. The mode of revascularization Carotid Artery Stenting (CAS) or Carotid Endarterectomy (CEA) has also been debated. Earlier trials showed favorable outcomes for CEA versus CAS, but more recent data with contemporary devices and more operator experience suggest equivalent outcomes. Though some clinical guidelines for the prevention of stroke concluded equipoise for CAS and CEA, the Centers for Medicare and Medicaid Services (CMS) only reimburse CAS for symptomatic patients at a higher risk for surgical complications, thereby limiting its usage. Whether symptomatic or asymptomatic, a patient-centered approach should consider medical management, CAS and CEA as complementary to each other.
2. Keywords: Carotid Artery Disease; Carotid Artery Stenting; Carotid Endarterectomy; Carotid Revascularization; Extracranial Carotid Disease
About 800,000 people in US have stroke
every year, 87% are ischemic .
It is estimated that 20% of ischemic strokes in the United States are caused by
carotid artery disease . Medical therapy only was previously
found inferior to CEA for symptomatic and asymptomatic patients. However, the
benefit of carotid revascularization in asymptomatic patients is being
revisited in this era of improved medical therapy . Six Randomized Clinical Trials (RCT)
have shown superiority of CEA over medical management only [3 each among symptomatic (NASCET, VACS, ESCT) [4-6] and asymptomatic patients (ACCT, VA, ACAS)] [7-9]. Of
note, these trials have systematically excluded patients with higher risk
profiles, which on subsequent assessments revealed mortality rates about three
times greater with CEA than reported .
CAS is now considered a viable alternative to CEA, and this article intends to
focus and review the evolution of CAS as a treatment option for extra-cranial
carotid artery disease, and the future of this therapy.
and Percutaneous Revascularization
High risk features for CEA is based on various
factors considered in randomized trials and it comprises of many
clinical and anatomic variables. Clinical variables include age > 75 - 80
years, congestive heart failure/ LVEF ≤ 30%,
coronary artery disease (left main or two-vessel disease/ MI in <30 days/
unstable angina/ need for cardiac surgery within 30 days), chronic obstructive
pulmonary disease, and renal insufficiency. High-risk anatomic variables
include inaccessible lesions at or above C2 spinal level or below the clavicle,
previous neck or head radiation therapy or neck surgery, spinal immobility,
restenosis after a previous/ unsuccessful CEA, contralateral laryngeal palsy,
presence of tracheostomy or contralateral carotid occlusion.
Among high-risk patients, outcomes of
CAS using contemporary techniques have been reported in the randomized trial SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High
Risk for Endarterectomy), various case
series, and registry data. Studies of high-risk patients have grouped
symptomatic and asymptomatic patients together and the trial eligibility was
based on exclusion criteria from prior CEA trials. The SAPPHIRE trial has been the only multicenter
randomized trial of high-risk patients, comparing CEA with CAS in both
symptomatic and asymptomatic disease. The results support the role of CAS with
EPDs when compared with CEA at 30-days, 1-year and 3-years follow-up [11,12]. Event rates were comparable between
CAS and CEA patients and it concludes that CAS with embolic protection is not
inferior to CEA in high-risk patients and provides equivalent long-term
protection from stroke events.
Registry data with independent
adjudication of neurologic outcomes in >6,000 high surgical-risk patients in
(EmboShield and Xact Post Approval Carotid
Stent Trial) and CAPTURE2 (Carotid RX ACCULINK/RX ACCUNET Post-Approval Trial to Uncover
Unanticipated or Rare Events) studies showed a death rate of 0.9%, and a
rate of stroke of 3.6% in EXACT and 2.8% in CAPTURE2 . These adverse event rates were lower
than prior registries (study populations ranged from approximately 200 to 500)
of carotid stenting with distal EPDs, suggesting CAS a safe and effective
option among high risk surgical patients [14-17].
The role of CAS in standard-risk
patients is yet to be conclusively determined, and the evidence base has
limitations. Given the lack of use of EPD and limited carotid stent usage, the
relevance of the CAVATAS trial data 
to contemporary practice is limited. Other trials including EVA 3S , SPACE  and ICSS  are limited by low CAS operator
A well-designed, NIH-funded CREST trial (Carotid Revascularization
Endarterectomy Versus Stenting Trial) enrolled > 2500 patients
including both symptomatic (53%) and asymptomatic, standard-risk patients.
Contrary to SPACE, EVA3S, and ICSS, there was a role-in phase to ensure
experienced operators. There was no statistically significant difference in the
primary outcome up to 4 and10 years after carotid revascularization [22,23]. During the
periprocedural period, though the incidence of the primary end point was
similar with carotid- artery stenting and CEA (5.2 and 4.5%, respectively;
hazard ratio for stenting, 1.18; 95% CI, 0.82 to 1.68; P = 0.38), the rates of
the individual end points differed between CAS and CEA groups [death, 0.7% vs.
0.3%; P = 0.18; stroke, 4.1% vs. 2.3%; P = 0.01 (driven by an increased
incidence of minor rather than major stroke); myocardial infarction, 1.1% vs.
2.3%; P=0.03]. (22) Over 10 years of follow-up,
there was no significant difference between patients who underwent stenting and
those who underwent endarterectomy with respect to the primary outcome. The
rate of post procedural ipsilateral stroke also did not differ between groups .
most recent trial among standard-risk patients comparing CEA and CAS is ACT1
(Asymptomatic Carotid Trial), which enrolled 1453 patients and revealed no
significant difference in the primary outcomes (death, stroke, myocardial
infarction at 30 days and ipsilateral stroke at 1 year) between the CAS and CEA
groups (P = 0.01 for non-inferiority) .
Current Guidelines for Carotid
The 2011 American College of Cardiology and American Heart
Association (AHA) are the most recent guidelines, endorsed by various societies
about the role of CAS in management of carotid disease, listed below; .
Ø CAS is indicated as an alternative to CEA for symptomatic
patients at average or low risk of complications associated with endovascular
intervention when the diameter of the lumen of the internal carotid artery is
reduced by more than 70% as documented by noninvasive imaging or more than 50%
as documented by catheter angiography and the anticipated rate of
periprocedural stroke or mortality is less than 6%. (Class I, Level of
Ø It is reasonable to choose CAS over CEA when
revascularization is indicated in patients with neck anatomy unfavorable for
arterial surgery (Class IIa, Level of Evidence: B),
Ø Prophylactic CAS might be considered in highly selected
patients with asymptomatic carotid stenosis (minimum 60% by angiography, 70% by
validated Doppler ultrasound), but its effectiveness compared with medical
therapy alone in this situation is not well established. (Class IIb, Level of
Although the debate will likely
continue, CREST and ACT1 appear to have restored confidence for CAS as a
treatment option for carotid disease. Looking forward, the randomized trial
CREST-2 is underway among patients with ≥70%
asymptomatic stenosis to assess the treatment differences between medical
management vs CEA and the treatment differences between medical management and
CAS. The medical management in both trials will include aspirin 325 mg/d for
the entire follow-up period. CAS
patients will be on dual antiplatelet therapy for 1-month post-procedure. The
primary risk factor targets include systolic blood pressure <140 mm Hg, and
LDL cholesterol <70 mg/dl, whereas the secondary risk factors modifications include
non-HDL cholesterol <100 mg/dl, hemoglobin A1c <7.0%, smoking cessation, targeted
weight management, and >30 minutes of moderate exercise 3 times a week. The primary
endpoint is the proportion of patients who experienced any stroke or death
within 44 days of randomization or ipsilateral ischemic stroke thereafter up to
4 years .
This trial is expected to be completed in 2020, and it may dictate the future
treatment strategy for asymptomatic patients with carotid disease.
Due to reimbursement restrictions, not
only is there a growing lag in innovation for CAS (the only update in recent
years is trans carotid stenting), but also compromise of operator experience.
Nonetheless, there are few recent developments to overcome the challenges with
CAS, most notably being trans carotid stenting and proximal embolic protection
Catheter manipulation of the aortic
arch in patients at high risk for traditional CEA adds to the risk of stroke
among CAS patients. To overcome this, transcarotid stenting is being studied - a
hybrid technique of carotid stenting, with a cut down and reversal of ante
grade flow in the Common Carotid Artery (CCA), External Carotid Artery (ECA)
and Internal Carotid Artery (ICA). This procedure provides protection against
embolization by avoiding endovascular manipulation within the aortic arch via
surgical CCA access and also by providing flow reversal in advance of any
manipulation of the lesion and throughout the stenting procedure. The ROADSTER
(Reverse Flow Used During Carotid Artery Stenting Procedure) trial enrolled
sixty-seven patients as lead-in cases, and 141 enrolled in the pivotal phase.
In the pivotal cohort, 26% were symptomatic and 74% were asymptomatic. Results
showed a technical success rate of 99%.
By hierarchical analysis, the all-stroke rate in the pivotal group was
1.4% (2 of 141), stroke and death was 2.8% (4 of 141), and stroke, death and MI
was 3.5% (5 of 141). One patient (0.7%) experienced postoperative hoarseness
from potential Xth
cranial nerve injury, which completely resolved at the 6-month follow-up visit . This may be a niche procedure for a patient
with a hostile arch and/or high-risk CEA anatomy, and a
complementary approach to existing carotid revascularization techniques. In
addition to flow reversal it facilitates management by operators less
comfortable with navigating arch and using embolic protection devices.
Proximal embolic protection devices
provide another tool to prevent embolization while undergoing CAS. Flow stasis
is established before crossing ICA lesion as the CCA and ECA are balloon
occluded, with the brain perfused through the circle of Willis.
In 14 European centers, 157 patients were enrolled in a prospective registry.
Protected carotid stenting was performed with the Mo. Ma™ system (Medtronic; Minneapolis, MN),
which occludes both the common and external carotid arteries via 2
independently inflatable compliant low-pressure balloons before any device is
advanced across the lesion. The observed in-hospital stroke/death rate was low
(2.5%). The 30-day death/stroke rate was 5.7% (9 patients) and the 30-day major
stroke/death rate was 1.3% (2 patients) .
The multicenter ARMOUR (ProximAl PRotection with the MO.MA Device DUring
CaRotid Stenting) trial evaluated the 30-day safety and effectiveness of the
prospective registry, enrolled 262 subjects from September 2007 to February
2009. The 30-day major adverse cardiac and cerebrovascular events rate was 2.7%
[95% CI (1.0 - 5.8%)] with a 30-day major stroke rate of 0.9%. No symptomatic
patient suffered a stroke during this trial .
In summary, though there is a potential for further
refinement of CAS tools/techniques, more important may be a re-evaluation of
the current paradigm for choosing patients for carotid revascularization. One
may also need to move beyond using symptomatic status and percent carotid stenosis
as the sole determinants of need for revascularization. Combining more
sophisticated prediction models incorporating various clinical variables along
with advanced imaging may allow a more accurate estimation of an individual's risk of any neurologic events. Finally, CAS, CEA, and medical therapy should
be considered as complementary therapeutic modalities for the treatment of
patients with carotid disease.
Citation: Rogers RK, Younas F (2018) Update on Percutaneous Management of Carotid Bifurcation Disease. Int J Angiol Vasc Surg: IJAVS-108. DOI: 10.29011/ IJAVS -108/100008