Enterprise stent for the treatment of symptomatic intracranial atherosclerotic stenosis: an initial experience of 44 patients

Approximately 5–10 % of all strokes and transient ischemic attacks (TIAs) are secondary to intracranial atherosclerotic disease (ICAD), whose incidence varies by race being more prevalent among Chinese, Japanese, African-Americans, and Hispanics [1, 2]. Although endovascular treatment emerged in the 1980s as a potential option for intracranial atherosclerotic stenosis (ICAS) with promising results upon device development and improvement [3, 4], its superiority to optimal medical treatment remains controversial [5]. In SAMMPRIS, the only randomized controlled trial (RCT) comparing the Wingspan stent and optimal drug therapy, Wingspan stent use was associated with a higher rate of perioperative complications [6]. Complex ICAS, i.e., that in tortuous vascular segments, long (>15 mm) lesions and/or arterial bifurcations, has been associated with higher rates of complications and renders particularly difficult the deployment of the Wingspan stent because of its high radial force and rigidity [7, 8]. The self-expanding, closed-cell Enterprise stent, which was originally designed for neck remodeling in the treatment of wide-necked intracranial aneurysms [9], appears better suited than the Wingspan stent for the treatment of complex ICAS because of its high flexibility, special carrier system structure [10] and reduced radial force [10], which is nonetheless sufficient to prevent elastic recoil and restenosis. In the study by Henkes et al. [11], treatment of intracranial atherosclerotic arterial stenosis with the Enterprise stent yielded a relatively lower in-stent restenosis rate than with the Wingspan stent; however, reperfusion hemorrhage and plaque shift in high-grade (>70 %) stenoses remained concerns. This paper reports the long-term safety and efficacy results of our single-center experience since we began in 2009 to use balloon dilatation and Enterprise stent deployment exclusively for the treatment of complex severe ICAS.

In this retrospective single-center study, undersized balloon angioplasty followed by stenting with the Enterprise stent appeared safe and effective in treating complex symptomatic ICAS, i.e., that in tortuous vascular segments, long lesions or bifurcations which render challenging deployment of the Wingspan stent and are associated with higher periprocedural risk rates. Use of the Enterpise stent in the latter setting was associated with a higher procedural success rate (100 %), lower rate of complications (perioperative stroke incidence, 9.1 %) and better long-term outcome (ISR rate, 6.8 %) than published results for the Wingspan stent.

The best treatment option for symptomatic intracranial atherosclerotic stenosis remains controversial [14, 15]. Results from WASID and SAMPPRIS studies suggested that optimal medical therapy may reduce the recurrence rate of stroke [6, 16]. Intracranial stents are also thought to minimize stroke recurrence by improving blood flow, especially for severe stenosis with serious hypoperfusion [17, 18]. Since 2000, many studies have reported the safety and efficacy of stenting for ICAD. Wingspan is currently the only self-expanding stent approved by FDA for ICAD treatment. Many single- and multicenter clinical studies have proven that stenting for ICAD is relatively safe, however, in the multicenter, randomized controlled SAMMPRIS trial, optimized medical therapy was superior to stenting combined with medical treatment in prevention of stroke for patients with ICAD.

Possible explanations for the higher periprocedural event rate in SAMMPRIS than in previous registries include higher stenosis severity and earlier treatment in SAMMPRIS (within 30 days of the qualifying event) [11, 19]. The design characteristics of the Wingspan stent also increased procedural difficulties and risks, particularly in tortuous vascular pathways, longer-segment lesions or cases involving arterial bifurcation [20‐22]. The LMA classification seems to be helpful in informing individual therapy and predicting stenting results. In cases with tortuous access pathways, it became difficult and dangerous to superselect or navigate the Wingspan system to the target the stenosis segment. Jiang and his colleagues reported a mortality rate of 0, 0, and 25 % for types A, B, and C lesions, respectively [13]. In this study, 21 patients (47.7 %) and 19 patients (43.1 %) were classified with type B and C morphology, respectively. All procedures were performed successfully without fatalities. According to LMA classification, 17 (38.6 %) and 5 (11.3 %) patients were classified as type II and III, respectively, by access. The high procedural success rate might be related with the design of the stent delivery system. The Enterprise self-expanding nitinol stent was originally developed for neck remodeling in the treatment of wide-necked intracranial aneurysms. The stent is introduced through a standard 0.021-inch inside diameter microcatheter and can be partially deployed as much as 70 % within the artery with the possibility of recapturing and redeployment if needed [23].

In a previous study, Henkes and his colleagues demonstrated that undersized balloon angioplasty and deployment of an Enterprise stent is safe and effective for intracranial stenosis, resulting in a rate of major complication of 7.7 % within 30 days post procedure. Several authors also investigated the safety and feasibility of drug-eluting stent placement for ICAD [24, 25], and albeit yielding better long-term patency rate, they are frequently too stiff to access distal stenosis lesions which might result in a penetration event. Although a relatively higher rate of periprocedural complications was observed in the present study, it may be related to the high grade of stenosis (>70 %) and the complicated stenosis lesions treated in the selected patients.

Atherosclerotic stenosis often involves the origin of a major artery [26]. In this study, the incidence of lesions involving bifurcation or ostium was 63.6 % (28/44). Balloon angioplasty or stenting may result in occlusion of branches due to the atheromatous components squashed into the origin of branches, especially in patients with type D, C, and F locations according to LMA classification, resulting in subsequent infarction. Thus, preprocedural evaluation such as wall imaging of targeted stenosis becomes necessary. Three of the complications of ischemic stroke that occurred in our study were related to occlusion of perforating arteries.

A high rate of ISR is the major limitation of intracranial angioplasty. The ISR rate of Wingspan procedures was reported to range between 7.5 % and 31.2 % [27]. Several factors may contribute to ISR, such as stent thrombogenicity, vascular injury by balloon dilatation, inflammatory reactions of the vessel wall, stent radial force, lesion length, as well as uncontrollable diabetes. Compared with Wingspan, the Enterprise stent exerts less radial force [10], and Zsolt et al. reported satisfactory ISR rates with the Enterprise stent (24.7 % restenosis during a mean 6.9 months of follow-up) compared with Wingspan stent [4]. In the present study, 3 (6.8 %) patients suffered ISR proved by DSA examination, two of whom received further intervention.

The present study has limitations inherent to its retrospective design and relatively small sample size for a 4-year enrollment period, which likely introduce selection bias. Prospective, multicenter, randomized controlled trials with longer-term follow-up and larger sample size are warranted.

This is a case series study of ICAS treated by Enterprise stent placement. Deployment of an Enterprise stent with undersized balloon angioplasty in the treatment of symptomatic intracranial atherosclerotic stenosis appears safe and effective, with a high technical success rate, relatively low periprocedural complication rate, and favorable outcome during follow-up.