What Is the Role of Transcarotid Artery Revascularization in the Treatment of Carotid Stenosis?

A 70-year-old man presented to the emergency department after two 5-minute episodes of right-arm weakness. Upon evaluation, all neurologic deficits had resolved. He previously smoked cigarettes, but otherwise had no known medical history. Imaging demonstrated a 90% or higher stenosis of the left internal carotid artery. You made a diagnosis of symptomatic carotid artery stenosis and recommended carotid revascularization in addition to best medical therapy, including an antiplatelet agent and statin. He asked, “What’s the best option?”

Carotid endarterectomy (CEA), initially described in the 1950s, remains the surgical gold standard for carotid revascularization. Plaque removal is performed through a neck incision with low perioperative complication rates and durable long-term reduction of stroke risk. Transfemoral carotid artery stenting (TF-CAS), popularized in the 1990s, is a treatment alternative to CEA. It can be performed percutaneously, under local anesthesia, and may be preferred for high-risk medical patients or those with unfavorable anatomy for CEA (e.g., as a result of prior neck surgery or radiation).

In 2015, the Food and Drug Administration (FDA) granted 510(k) clearance — an expedited approval process that allows a company to market a new medical device if it is deemed substantially equivalent to another FDA-approved device — for transcarotid artery revascularization (TCAR) as a third procedural option for high-risk patients with carotid stenosis^1,2 (Fig. 1 shows the three revascularization strategies). In 2022, FDA approval was extended to make the option available to standard-risk patients.³ TCAR is a hybrid procedure during which a stent is placed directly into the carotid artery through a small incision at the base of the neck.⁴ The procedure utilizes an extracorporeal circuit to establish flow reversal in the internal carotid artery for cerebral protection. TCAR may serve as a useful therapeutic alternative for select patients, such as those with prior neck surgery (high risk for CEA) or a diseased aortic arch (high risk for TF-CAS); however, the long-term durability and effectiveness of this newer procedure remain uncertain.

Carotid revascularization paradigms have historically been informed by high-quality evidence. Use of CEA for stroke risk reduction is predicated on robust data derived from randomized controlled trials. Meta-analyses suggest a 30 to 50% relative reduction in stroke risk over medical therapy alone among appropriately selected patients.^5,6 Although medical therapy has irrefutably improved over time, likely decreasing this effect, the demonstrable stroke reduction benefit has led the American Heart Association to support CEA for appropriately selected individuals with 70% or higher carotid stenosis.⁷

Likewise, the utility of TF-CAS has also been informed by several high-quality randomized trials comparing its performance with that of CEA.^8,9 These studies demonstrated that the periprocedural risk of stroke seems to be greater for TF-CAS than for CEA, with similar stroke rates beyond the initial periprocedural period.^8,9 Accordingly, the American Heart Association recommends TF-CAS as an alternative to CEA for select patients at low or average risk of complications with stenting.⁷

In contrast to the high-quality trial data surrounding CEA and TF-CAS, no randomized trial evidence exists regarding TCAR. With no enrolling randomized trials, clinicians are relying on observational studies to inform therapeutic decision-making. Industry-sponsored single-arm prospective TCAR studies have documented a 1.9% perioperative stroke risk,⁴ whereas registry-based analyses demonstrated an in-hospital stroke risk similar to that of CEA (1.4% for TCAR vs. 1.4% for CEA)¹⁰ and a decreased in-hospital stroke risk compared with TF-CAS (1.3% for TCAR vs. 2.4% for TF-CAS).¹¹ However, long-term durability is not defined, and the roles of selection bias and unmeasured confounding in these nonrandomized studies remain difficult to quantify.

Nevertheless, in 2020, TCAR already represented 17% of carotid revascularization procedures at centers that offered it.¹² By June 2021, TCAR had been performed in more than 21,000 patients across nearly 500 centers.¹³

A randomized trial would be the optimal study design to define the safety and efficacy of TCAR. Several possible trial options exist. One feasible design is to model a trial after the actively enrolling Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2; ClinicalTrials.gov number, NCT02089217), which are two parallel trials of CEA versus best medical therapy and TF-CAS versus best medical therapy for asymptomatic patients with carotid stenosis.¹⁴ The primary outcome in CREST-2 is stroke or death within 44 days of randomization or ipsilateral stroke up to 4 years.¹⁴ Each of the two trials plans to enroll 1240 participants with 70% or higher carotid stenosis.¹⁴ Unfortunately, the design of CREST-2 does not include TCAR¹⁴; therefore, a randomized trial of TCAR would ideally be developed to compare best medical therapy, CEA, TF-CAS, and TCAR. Only then can we define the efficacy and safety of TCAR versus established mainstays of therapy. In such a trial, we would additionally consider enrolling symptomatic patients, which may necessitate fewer participants.^4,5,8 We would also require carotid stenosis severity to be defined by computed tomography angiography, given the documented variation in duplex ultrasound criteria used across the United States.¹⁵

The already widespread adoption and utilization of TCAR will likely make sufficient enrollment for any such trial more difficult than it would have been had a trial been conducted before TCAR’s FDA approval. This underscores the important role of using high-quality observational studies and/or registry data to inform clinical decision-making when high-quality level 1 evidence is unavailable. However, observational work should not serve as an equivalent substitute for a randomized trial. Accordingly, there remains an ongoing need for a comparative trial to guide clinical practice and the optimal role of TCAR.

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