Carotid artery stenting: it's all about appropriate patient selection and keeping to the indications

Abstract

With increasing carotid artery stenting (CAS) expertise and improved CAS equipment, recent trials have demonstrated better results for CAS compared with earlier studies. As a result, it may be argued that CAS is currently non-inferior to carotid endarterectomy (CEA), at least in some patient subgroups. Consequently, there have been recent calls for extending CAS indications to include average surgical risk patients with symptomatic or asymptomatic carotid stenosis. However, CAS remains a less cost-effective option than CEA. Opening the floodgates to unrestricted CAS for both symptomatic and asymptomatic carotid patients would have considerable cost implications for any health system. Appropriate patient selection and keeping to the indications are crucial to optimize CAS outcomes.

Keywords::

• carotid artery stenting
• carotid endarterectomy
• stroke
• symptomatic

The optimal management of patients with carotid stenosis is a highly controversial issue and subject to extensive debate [1,2]. In the last few years, carotid artery stenting (CAS) has repeatedly challenged and attempted to replace the ‘gold standard’ of carotid endarterectomy (CEA) as the treatment of choice for symptomatic carotid artery stenosis. In a previous issue of Expert Reviews of Cardiovascular Therapy, Hawkins et al. discussed the specific characteristics that render patients with carotid artery stenosis at higher stroke risk with CAS than with CEA [3]. Increasing age and symptomatic status are the most robust predictors of clinical events after CAS, whereas certain anatomic/physiologic criteria (e.g., a type III aortic arch, the presence of aortic arch atheroma, an angulated distal internal carotid artery) increase the difficulty of performing a straightforward procedure, thereby increasing CAS risk [3].

Early randomized trials comparing CAS versus CEA in symptomatic patients reported inferior results for CAS [4–7]. Differences in carotid plaque morphology and a higher incidence of microemboli during CAS compared with CEA in symptomatic patients may account for these inferior results. However, it was recognized that improvements in CAS technology (mesh covered stents, reversal of flow embolic protection and transcervical approaches), better patient selection, centralization of CAS procedures and improvements in CAS expertise could enhance CAS outcomes in the future [4–8].

According to some recent guidelines, CAS rather than CEA is recommended in certain symptomatic patients with >50% stenosis who are considered at high surgical risk for anatomical reasons, for example, those with tracheal stoma and scarred necks from radiotherapy or surgery [9–11]. In addition, CAS is recommended in symptomatic patients with severe comorbidities (such as severe uncorrectable coronary heart disease, congestive heart failure or chronic obstructive pulmonary disease) [9–11]. It may be argued that these recommendations are arbitrary and not supported by conclusive evidence. For example, a recent report challenged the hypothesis of ‘high-risk candidate for CEA’ and demonstrated excellent results with CEA in such ‘high-risk’ patients [12]. Another report supported that the current criteria for CAS overestimate its efficacy in symptomatic patients and in individuals at high surgical risk [13]. This single-center, non-randomized, retrospective cohort study compared the outcomes of patients undergoing CAS (n = 271) versus CEA (n = 830) during a 6-year period. Among symptomatic patients, physiologic high-risk status (age >80 years, congestive heart failure, left ventricular ejection fraction <30%, unstable angina, a history of myocardial infarction ≤30 days before, hemodialysis, severe lung disease, contralateral carotid occlusion and before or after coronary artery bypass graft/valve repair) was associated with increased stroke/death rates in patients undergoing CAS compared with CEA (14.3 vs 2.7%, respectively; p < 0.01). Furthermore, anatomic high-risk status (contralateral laryngeal nerve palsy, carotid restenosis, history of neck irradiation, high or lesion and prior neck surgery) was associated with a trend toward increased stroke/death rates in CAS versus CEA patients (16.1 vs 0.0%, respectively; p = 0.14). Finally, among symptomatic patients undergoing CAS, patients with physiologic and anatomic high-risk factors had higher stroke/death rates compared with non-high-risk CAS patients (14.3 vs 0.0% and 16.1 vs 0.0%, respectively; for both p ≤ 0.05) [13]. These results demonstrate that CAS may not be a preferable option over CEA in patients considered as ‘high risk’, and at least some of these extremely high-risk patients are probably best treated by intensive medical therapy without any intervention.

Another area where CAS has received intense criticism is the applicability of the results of clinical trials in the ‘real-world’ setting; in other words, the ability to replicate the results of CAS clinical trials outside these trials. A well-conducted study used the Nationwide Inpatient Survey data files from 2005 to 2009 (n = 81,638 CAS patients) [14]. Of these, 16,078 (19.6%) patients underwent the procedure as part of a clinical trial. The mean age of the patients, the proportion of women and non-whites treated with CAS as part of a clinical trial were all lower compared with those treated outside clinical trials. Furthermore, the in-hospital mortality was >twofold higher among patients treated with CAS outside compared with inside clinical trials (1.12 vs 0.53%, respectively; p = 0.0005). Finally, the composite end-point of stroke, cardiac events and death was significantly (p = 0.02) higher among patients treated with CAS outside versus inside clinical trials [14]. Based on these and other results, a group of stroke-prevention clinicians from the USA and other countries advised the Centers for Medicare and Medicaid Services not to extend the current reimbursement indications for CAS, as this would have negative health and economic consequences for the countries that would follow such an inappropriate action [15–19].

Some authors have supported extending the indications of CAS to include patients with asymptomatic carotid artery stenosis [20–22]. The arguments supporting this recommendation are that CAS is associated with low stroke/death rates and also improves the neurocognitive performance of asymptomatic carotid patients [20–22]. However, it has been argued that most asymptomatic patients should be managed by best medical therapy alone and that neither CAS nor CEA should be routinely offered to these patients because of the large number of patients that require treatment to prevent one stroke [23,24]. Until the optimal management of asymptomatic carotid patients is resolved, the use of CAS for most asymptomatic patients should be considered questionable, and certainly not one that should be funded by healthcare organizations. On the other hand, it is clear that recent CAS registries have demonstrated better outcomes compared with earlier ones. Improvement in clinical outcomes with CAS has been associated with the development of embolic protection devices, namely proximal flow reversal (e.g., the Mo.Ma^® Ultra flow interruption device, Medtronic, Invatec S.p.a., Roncadelle, Italy [25] or the Gore^® Parodi Anti-Embolic System, W.L. Gore, Flagstaff, AZ, USA) [26,27] and distal filter protection devices (e.g., the FiberNet distal filter system) [28]. Proximal embolic protection devices achieve external and common carotid artery endovascular occlusion, thus resulting in cessation or reversal of blood flow. This technique is associated with a very low stroke incidence and thus improved CAS results. Some studies have reported better results with flow reversal devices than with filters [29,30]. However, the benefits of flow reversal have not been observed universally [31–33].

Another way to achieve better outcomes with CAS is by using an approach other than the classic one via the femoral artery. The performance of CAS via the femoral approach may be difficult or even impossible due to the presence of extensive aortoiliac occlusive disease or anatomic variations of the aortic arch (e.g., bovine aortic arch). In such patients, a different approach might offer advantages and better outcomes. For example, in patients with a bovine aortic arch and left internal carotid artery stenosis, a right radial or brachial approach may be associated with better outcomes [34]. Another approach which has gained favor in the last few years is the transcervical route. A recent systematic review showed that CAS via the transcervical approach is a safe procedure that is associated with a low incidence of stroke and complications [35].

In conclusion, recent advances in CAS (e.g., flow reversal, transcervical approach, better stents, etc.) may improve CAS results and render CAS an appropriate ‘alternative’ to CEA at least in specific patient subgroup. Implementation of best medical therapy [1,36–38], appropriate patient selection and keeping to the right indications are crucial to optimize CAS outcomes. All physicians performing CAS or CEA should keep an independently audited record of their outcomes because patient benefit depends upon low complication rates.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.