Transcarotid Artery Stenting: Hype or Hope?

Abstract

HomeStrokeVol. 53, No. 1Transcarotid Artery Stenting: Hype or Hope? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBTranscarotid Artery Stenting: Hype or Hope? Gert J. de Borst, MD, PhD Gert J. de BorstGert J. de Borst Cotrrespondence to: Gert J. de Borst, MD, PhD, Department of Vascular Surgery G04.129, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, the Netherlands. Email E-mail Address: [email protected] https://orcid.org/0000-0002-1389-4141 Department of Vascular Surgery G04.129, University Medical Center Utrecht, the Netherlands. Search for more papers by this author Originally published7 Dec 2021https://doi.org/10.1161/STROKEAHA.121.036464Stroke. 2022;53:108–110This article is a commentary on the followingIn-Hospital Outcomes of Urgent, Early, or Late Revascularization for Symptomatic Carotid Artery StenosisOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 7, 2021: Ahead of Print See related article, p 100Carotid endarterectomy (CEA) remains the safest method of revascularization within the urgent (<48 hours) period after symptoms. That is the main conclusion of the recent Vascular Quality Initiative analysis on in-hospital outcomes in symptomatic patients comparing transcarotid artery revascularization (TCAR), transfemoral carotid stenting (TFCAS), or CEA performed within different time intervals after the most recent symptom.1 This analysis is an important new step in assessing the true additive value of TCAR to our treatment armamentarium of carotid disease, especially for symptomatic patients.Thus far, in randomized controlled trials (RCTs) comparing endovascular revascularization versus surgery, only transfemoral techniques were included while no comparative studies of TCAR versus CEA have yet been performed. A meta-analysis of pooled data from RCTs on symptomatic patients revealed a significantly higher risk of procedural nondisabling ipsilateral stroke with TFCAS than with CEA.2 TFCAS was also associated with a 4× higher procedural risk of new ischemic brain lesions measured by diffusion-weighted magnetic resonance imaging (DW-MRI).3Without exception, all RCTs have now shown that beyond the 30-day period, severe restenosis was rare, while the long-term risk of any stroke following either TFCAS or CEA appeared to be virtually the same.2 The key message, therefore, is that the magnitude of the initial procedural risk remains the single most important factor to determine the optimal revascularization technique (endovascular versus open surgery) in terms of stroke-free survival.4 To put it simply, if the procedural risk related to carotid stenting can be further reduced, stenting will assume an ever increasing role in clinical practice. This reduction in procedural risk might be achieved through patient selection and further evolution in stent design and catheterization routing. It is here that TCAR was initially designed as an alternative to TFCAS to avoid aortic arch manipulation and related embolic stroke and DWI lesions. TCAR data appeared in 104 reports in the last 5 years of which 57 in the last 12 months (Pubmed, July 2021) including 6 reviews and meta analyses. Several cohort series and single-arm trials have claimed favorable procedural stroke/death rates for TCAR as compared with TFCAS. Still, there are several elephants in the room that need to be discussed before TCAR can fulfill a more generalizable role5:No RCT has compared TCAR with either CEA or TFCAS (and this was disregarded in most of the published reviews);The quality of the studies is very modest. The Methodological Index for Non-Randomized Studies score classified studies (6/18) as moderate or poor quality (12/18). No high-quality study has yet been performed;Most of the registry cohorts to evaluate TCAR were dominated by inclusion of asymptomatic patients;Proper comparison of TCAR versus CEA in symptomatic patients only has thus far not been performed;Most data were derived from company-sponsored single-arm studies or comparative analyses with historical controls;Three-quarters of the patients of all available data originate from the Vascular Quality Initiative registry limiting generalizability of outcome;Data on compliance with the instructions for use are mostly lacking;Anatomic suitability and exclusion criteria for TCAR have been underreported. One-fourth of patients may be unsuitable for TCAR because of anatomic restrictions such as a short neck or flow reversal intolerance;In TFCAS, the pathophysiological mechanism of 30-day stroke (in one-third of the cohort) was hemodynamic. While TCAR may reduce the risk of embolic stroke, it cannot diminish the risk of hemodynamic stroke;Patient preference and cost-effectiveness would come into play once noninferiority of TCAR relative to CEA could be proven.The study by Cui et al1 still carries many of the above limitations (retrospective analysis, nonrandomized and registry data) but does bring an important message, as this study now for the first time reports selectively on symptomatic patients only and introduces the crucial item of timing in relation to TCAR outcomes. The second claim of the authors, however, that among revascularization performed outside of the 48 hours TCAR and CEA have comparable outcomes cannot be hold based on the data provided. The reported in-hospital procedural outcomes do not unequivocally document the value of TCAR (1) because no direct comparison with either TFCAS or CEA was performed and (1) as in-hospital outcome may underscore true procedural outcome as over one-quarter of perioperative strokes occur following discharge (after both carotid artery stenting and CEA).Inherent to the nonrandomized Vascular Quality Initiative data source, and potentially due to selection bias, relative numbers per time cohort were unbalanced. Out of 2006 cases in the urgent group, only 144 received TCAR. TCAR was also underrepresented in the early and late cohorts at a rate of 1:4 versus CEA.Of even more relevance, CEA patients had a more severe clinical presentation in all time groups. Patients undergoing TCAR presented with stroke in 49.3% in the urgent group and 50.7% in the late group, versus 72.7% and 66.7% in the CEA group respectively. A registry-based study found a perioperative stroke/death rate of 5.5% in patients presenting with stroke versus 2.4% or 2.8% in TIA or ocular TIA patients, respectively.6 As the relative proportion of patients with a preprocedural stroke versus those with a hemispheric or ocular TIA will affect the overall outcome for all symptomatic patients, outcome analyses need to be corrected for type of presenting symptom.Most guidelines now recommend that carotid revascularization should be undertaken within 14 days of the index event, whereas some advocate 48 hours.7 At the time, the 2-week threshold was arbitrarily selected for methodological convenience rather than having any clinical relevance. Unfortunately, there are very few high-quality data on the outcomes in patients undergoing urgent (<48 hours) or early (<2 weeks) revascularization. Of the RCTs, the Carotid Revascularization Endarterectomy Versus Stenting Trial reported the shortest median interval still being 22 days for CEA and 18 days for CAS. In all except 2 RCTs, the mean delay from the index event to revascularization was >1 month.8 As a consequence, in a pooled analysis of individual patient data (n=4.138) from 4 randomized trials, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). TFCAS within 7 days was associated with a 5-fold excess risk (8.3% versus 1.3%) of procedural stroke compared with CEA and a 2-fold excess risk (7.1% versus 3.6%) when performed between 8 and 14 days. No granular data on outcome <48 hours was available. Single-center data previously reported a 4.4% death/stroke rate in 206 patients who underwent CEA ≤48 hours of symptom onset suggesting that patients can safely undergo CEA in the hyperacute period.9Based on data by Cui et al revealing acceptable stroke rates of 4% for urgent CEA versus >6.5% stroke rate for the stenting techniques in the urgent phase, and suggesting safer outcomes with delayed stenting, it may perhaps not be surprising that a comfort zone may evolve where there is little or no impetus for urgent revascularization, offset by the consequences of increased procedural risks. This is a harmful assumption, as at all times, the fear for the potential increased procedural risks needs to be outweighed against the proven benefits of intervening early. The logistics of providing a comprehensive revascularization service are substantial in many health systems. In the Dutch Audit for Carotid Interventions, registering 6459 patients by 52 hospitals, the majority (4832; 75%) were treated <14 days.10 Surprisingly, in the Vascular Quality Initiative data set, roughly half the symptomatic patients undergoing revascularization were treated beyond the 14-days threshold. The move toward expedited interventions clearly poses a considerable challenge. Reducing the overall waiting time most probably will prevent more strokes than debating the specific type of revascularization technique applied. Meanwhile, the omission of high-quality data regarding TCAR outcomes stratified for delay means that guidelines will continue to recommend CEA as the first-choice intervention in the early time period.7,11 Further, for the first time, a very recent guideline now adopted lower risk thresholds for procedural strokes in symptomatic patients (4% instead of 6%). Clearly this creates an even greater gap between accepted versus observed stroke rates with early stenting.11In CAS patients, higher age, plaque vulnerability, and complex carotid/aortic arch anatomy have been identified as risk factors.3,12 In mostly symptomatic patients, new ischemic brain lesions were identified on repeat examination at 24 to 48 hours after 4 (12.9%) TCAR versus 11 TFCAS procedures (33.3%; P=0.03). Unfortunately, the timing of the intervention (relative to the index event) was not reported. A small pilot study (TCAR versus CEA versus TFCAS, 16 versus 10 versus 8 patients) using intraoperative transcranial Doppler found that TCAR was associated with a significant lower rate of embolization as compared with TFCAS but not with CEA. However, no study has ever compared post-TCAR with post-CEA DW-MRI. It remains to be seen whether flow reversal can reduce the prevalence of new DWI lesions below the rate observed in CEA.12There is no doubt that carotid stenting has evolved considerably during the last 2 decades, but for now, CEA remains safer than stenting for most patients in all periods after onset of symptoms. So how can TCAR establish a generalizable and safe role in a real-world setting? At all times, as a prophylactic procedure, carotid revascularization should occur early after index symptoms to prevent as many strokes as possible. Although the current evidence is promising, independent and preferentially investigator-driven well-designed randomized controlled studies comparing TCAR with CEA in recently symptomatic patients are necessary to establish the true value of TCAR in carotid revascularization.Disclosures None.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 110.Cotrrespondence to: Gert J. de Borst, MD, PhD, Department of Vascular Surgery G04.129, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, the Netherlands. Email g.j.[email protected]nl