3.1 Introduction

Flow diversion is the technique of endoluminal reconstruction of the parent artery with a low-porosity stent leading to aneurysm thrombosis followed by neointimal growth across the aneurysm neck. It represents the latest technique in the cerebrovascular specialist′s armamentarium for the treatment of complex and difficult-to-treat aneurysms, particularly wide-neck aneurysms, giant aneurysms, and aneurysms with fusiform morphology. The majority of flow diverters have received CE mark and Food and Drug Administration (FDA) approval for the treatment of aneurysms of the internal carotid artery (ICA) below the circle of Willis. In addition, there is a growing body of literature investigating flow diversion for the treatment of anterior and middle cerebral artery aneurysms and aneurysms involving the posterior circulation. In this chapter, we discuss the current regulatory approval status of flow diverters, as well as published occlusion rates for on-label and off-label applications.

3.2 Brief Overview of Flow Diverters—Approval Status and Indications

Flow diversion is one of the fastest growing areas in neurointervention, and new or updated devices are in constant development. This chapter focuses on four principal flow diverters: the Pipeline Embolization Device (PED; ev3/Covidien, Irving, CA), the SILK/SILK + (SFD; Balt Extrusion, Montmorency, France), the Flow Redirection Endoluminal Device (FRED; MicroVention, Tustin, CA), and the Surpass flow-diverting stent (SUR; Stryker Neurovascular, Fremont, CA).

Currently, the PED is the only flow diverter approved by the FDA for use in the United States. The PED and the other devices discussed have received CE-mark approval for use in the European Union. A detailed overview of the technical specifications of these devices may be found in Chapter 9. The approval status and indications for these devices are summarized in Table 3.1.

3.3 Literature Review and Analysis of Occlusion Rates

Various grading schemes have been published to evaluate the degree of occlusion for aneurysms treated with endovascular techniques. ¹ , ² , ³ Several new grading scales specific to flow diversion have been proposed and are discussed in Chapter 13. At present, no one system is in universal use. The reports reviewed in this chapter use variously the Roy and Raymond scale, the O′Kelley-Marotta scale, Kamran-Byrne scale, or simply the authors’ own evaluation of complete versus incomplete occlusion. Owing to variability across studies as well as degrees of partial aneurysm occlusions across reports and devices, using a unified scale is not possible. Thus, only complete occlusion rates are presented in this review.

3.4 Anterior Circulation—Internal Carotid Artery Below the Circle of Willis

Three landmark trials have established the role of flow diverters, in particular the PED, for the treatment of giant, wide-neck, and fusiform aneurysms of the ICA: Pipeline for the Intracranial Treatment of Aneurysms (PITA), Lylyk and colleagues’ “Buenos Aires Experience,” and the Pipeline for Uncoilable and Failed Aneurysms trial (PUFs). ⁴ , ⁵ , ⁶ The study by Lylyk et al, termed the Buenos Aires experience, was a prospective, all-inclusive case series of 63 predominantly anterior circulation aneurysms of the ICA, though 8 aneurysms were located in the posterior circulation. Approximately half of aneurysms studied were large or giant, wide-neck (dome-to-neck ratio of < 2 or neck ≥ 4 mm) lesions of the cavernous and paraophthalmic region. Sixty-three percent of aneurysms treated were unruptured and untreated lesions, while the remainder had previously been treated with subsequent recanalization. Seven previously ruptured and previously treated aneurysms were included. Seventy percent of aneurysms were treated with a single PED, while 30% were treated with multiple devices. Only four patients were treated with adjunctive coil embolization, all of whom had only a single PED placed. At 6-month follow-up angiography, 93% of patients demonstrated complete occlusion.

This successful trial was affirmed with two subsequent prospective single-arm trials: PITA and PUFs. ⁴ , ⁶ PITA included 31 patients harboring mostly sidewall aneurysms of the ICA with an average size of 11.5 mm. Fifty-two percent of aneurysms underwent adjunctive coil embolization. PUFs were more restrictive in aneurysm location and morphology, including 106 wide-neck (≥ 4 mm) aneurysms of the ICA at least 10 mm in diameter. Aneurysm location was limited to the ICA from the petrous segment to the superior hypophyseal segment. Only a single patient underwent combined flow diversion and coil embolization within the study, though six aneurysms had been previously coiled. A median of three PEDs were used per aneurysm. Both the PITA and PUFs trials demonstrated occlusion rates at 6-month follow-up of 93.3 and 73.6%, respectively. The occlusion rate in PUFs increased to 86% at 12 months, suggesting that angiographic cure may be prolonged in patients who undergo flow diversion alone without adjunctive coil embolization. These studies are summarized in Table 3.2.

Many additional studies have evaluated efficacy of the PED in the anterior circulation. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ Most published studies to date have not excluded patients based on aneurysm location, and as a result, many publications include a small number of aneurysms either in the posterior circulation or aneurysms distal to the superior hypophyseal artery. Occlusion results from these trials are generally favorable with complete angiographic occlusion ranging from 55.7 to 92% ( Table 3.3). ⁷ , ⁹

While the PED remains the most popular flow diverter in use in the United States, several trials have evaluated the Silk/Silk + (SFD), Surpass (SUR), and FRED for aneurysms of the ICA.

Eight major studies investigating the SFD have been published to date. ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ Most studies included aneurysms in an “all-comers” fashion, though most aneurysms were previously ruptured and coiled or unruptured, untreated, large, or giant aneurysms of the ICA. Most series also contain a minority of posterior circulation aneurysms. Many of the patients underwent adjuvant coil embolization due to a 2010 BALT safety advisory and update to the instructions for use (IFU) that warned of an increased risk of rupture with SFD deployment without adjunctive coil embolization. One study included patients treated with both the SFD and other conventional stents including coronary stents and the LEO stent (Balt Extrusion, Montmorency, France). ¹⁶ Occlusion rates for the SFD in the aforementioned applications ranged from 49% at 1 month to 87.8% complete occlusion at a mean follow-up of 17.8 months, reflecting the trend of higher occlusion rates with longer follow-up times. ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ Notably, one study reported a 23% recanalization rate of previously occluded aneurysms treated with flow diversion without adjuvant coil placement. ¹⁹ No aneurysms in this study treated with the SFD with adjuvant coiling recanalized. This observation confirmed the need for long-term angiographic follow-up and supported BALT′s revised IFU, which instructs users to perform coil embolization in conjunction with stent placement. Details of the aforementioned studies are highlighted in Table 3.4.

While several reports of the FRED flow diverter have been published to date, only one study sufficiently limits inclusion criteria to include predominantly anterior circulation aneurysms isolated to the ICA. ²⁰ , ²¹ , ²² Kocer et al reported a single-center experience with 33 patients with wide-neck, saccular, and fusiform aneurysms predominantly of the ICA proximal to the origin of the anterior choroidal artery; however, 2 patients with dissecting fusiform aneurysms of the vertebral arteries were included. They reported a complete occlusion rate of 67 and 80% at 3- and 6-month follow-up, respectively. This study is limited by incomplete follow-up, with only 8 of 33 patients with 12-month follow-up. Of these eight, 100% of aneurysms were completely occluded at 12 months. ²²

Relative to the PED and SFD, published experience with the Surpass flow diverter for aneurysms of the ICA is limited. de Vries and coauthors published a prospective single-center study of 37 patients with aneurysms in the anterior and posterior circulation and the middle cerebral artery (MCA). The majority of cases consisted of saccular aneurysms located within the ICA from the cavernous through ophthalmic segments. Adjuvant coils were used in two patients. They reported a complete occlusion rate of 94% at 6 months. ²³ The largest published series included 165 patients with wide-neck, saccular aneurysms of the cerebral circulation. In this series, 22% of aneurysms were distal to the circle of Willis and 14.5% in the posterior circulation. The authors reported a complete occlusion rate of 75%, which improved to 78% when only anterior circulation aneurysms were included. ²⁴