Flow Diversion of Posterior Circulation Aneurysms: Systematic Review of Disaggregated Individual Patient Data

DISCUSSION

The experience of flow diversion for the treatment of posterior circulation aneurysms is relatively limited compared with the anterior circulation. For example, the most recent published meta-analysis by Liang et al¹⁰ combined 12 studies comprising 358 posterior circulation aneurysms treated with the PED to yield an 82% obliteration rate with an 18% complication rate. Posterior circulation aneurysms, however, represent an anatomically diverse group of aneurysms, with differing morphologic subtypes and technical challenges. To further investigate factors associated with the safety and efficacy of this treatment in posterior circulation aneurysms, we performed a systematic review of the literature to collect disaggregated, patient-level data and identified 301 individual cases of posterior circulation aneurysms treated with endoluminal flow diversion. This is the largest series of case-reported data to date, permitting more granular analysis of variables associated with complications, occlusion rates, and outcomes. Our findings reveal complications in 22%, angiographic occlusion in 65%, and good outcomes in 67%. Age, aneurysm size, prior treatment, and the number of flow diverters were significantly and independently associated with clinical and radiographic outcomes. We then performed a meta-analysis of prior large (≥10 patients) series,^{12⇓⇓⇓⇓⇓-18} demonstrating that our results are in line with prior aggregated studies and revealing an overall complication rate of 19.6% and a 75.2% occlusion rate (Fig 2).

Prior studies have shown that flow diversion in the posterior circulation can be performed successfully, albeit with higher inherent risks than in the anterior circulation. Several factors associated with complications and outcomes have been identified, including size, morphology, and the involvement of critical perforators.¹⁹ As part of their meta-analysis, Liang et al¹⁰ performed a meta-regression analysis and found that age was the only identifiable factor associated with angiographic outcomes. They found no factors associated with complications. The largest study in that meta-analysis was by Griessenauer et al,¹⁴ who reported a retrospective multicenter series of 129 patients with posterior circulation aneurysms treated with the PED. They analyzed aneurysms separately by morphology (saccular, fusiform, and dissecting) and found very few factors associated with angiographic outcomes or complications. In fact, the only significant variable found on multivariate analysis was clopidogrel responsiveness, which was associated with complications in saccular aneurysms.

More recently, Lopes et al¹⁶ reported a subgroup analysis of posterior circulation aneurysms from the International Retrospective Study of Pipeline Embolization Device (IntrePED) trial, a multicenter retrospective PED registry. They identified 91 patients with a mean follow-up of 21 months. Multivariate analysis identified fusiform morphology and the use of ≥3 PEDs as factors associated with combined neurologic morbidity and mortality. Aneurysm size was separately associated with morbidity, while the use of ≥3 PEDs, rupture status, and age were associated with mortality. Our data are consistent with these prior studies in that multivariate analysis identified only a few factors associated with outcomes. Increasing age was uniformly associated with higher procedural complications and poorer angiographic and functional outcomes, and advanced age has been associated with increased complications with interventional procedures in general.²⁰ Similar to findings in the IntrePED subgroup analysis,¹⁶ multiple FDs were associated with increased complications and poor functional outcomes in our systematic review. Deployment of multiple FDs increases the technical complexity of an intervention and has been associated with a higher risk of complications in prior studies,²¹ though a more recent analysis of this topic found no difference in complications with increasing PEDs.²² The important association of multiple flow diverters with both complication rates and outcomes on multivariable analysis may indicate that this factor is a more relevant marker of aneurysm complexity than size, location, or morphology alone. However, these findings should not discount the importance of size, location, and morphology, and additional studies will be required to further investigate these factors.

Most important, while we found no significant differences in outcomes among aneurysms of different locations on multivariable analysis, significant differences in complication rates and outcomes across aneurysm locations were found on univariate analysis (Online Supplemental Data and Fig 1). These univariate differences highlight the different pathologies, anatomy, and technical challenges of treatment with flow diversion predicted by each posterior circulation aneurysm subtype. For example, VBJ and basilar trunk aneurysms have poor natural histories^23,24 but also pose significant treatment challenges regardless of treatment technique.^24⇓-26 In our series, these aneurysms had the highest proportions of giant and fusiform morphologies and were treated with the greatest number of FDs. They, similarly, had the poorest outcomes (Fig 1). Conversely, vertebral artery aneurysms have a relatively benign natural history,²⁷ and endovascular treatment is known to be safe and effective.²⁸ Other unique challenges encountered in the posterior circulation include the bifurcation configuration of basilar apex aneurysms, which were the most likely to require adjunct coiling in our series, and distal locations of PICA and PCA aneurysms.

In the United States, the use of the PED for posterior circulation aneurysms remains off-label, though this device was used in most cases (85% in our series). Similarly, the FRED is approved in the United States for use with wide-neck and fusiform internal carotid artery aneurysms from the petrous segment to the terminus. The Surpass Streamline Flow Diverter has approval for the treatment of unruptured large and giant wide-neck intracranial aneurysms, including those in the posterior circulation. Other flow-diverting devices, including the p64, Derivo, and Tubridge are not yet approved for use in the United States. The decision to use flow diversion to treat posterior circulation aneurysms must be made in the context of other possible treatments. Before the widespread use of flow diversion, several studies evaluated the safety of surgical management,^26,29,30 which includes direct clipping or reconstruction, as well as proximal occlusion, bypass occlusion, and wrapping. Reported favorable neurologic outcomes range from 55% to 90%, depending on location and series.²⁶ Before flow diversion, endovascular options included primary coil embolization, stent- or balloon-assisted coil embolization, and vessel sacrifice. Favorable outcomes for endovascular treatment similarly range from 67% to 100%, again depending on location.²⁶ The ultimate choice of treatment technique must be based on individual anatomic, patient, and treating physician factors. Off-label use of flow diversion should be discussed with patients, even if it is considered the optimal treatment method.

We acknowledge several limitations to this study design. First and foremost, this systematic review identified data from case reports or small series and is, therefore, susceptible to publication bias. Case reports are often published to describe a novel approach, an unusual disease presentation, a notable complication, or an exceptional treatment outcome. Given the relative rarity of flow diversion for posterior circulation aneurysms and the novelty and controversy of this treatment in this population, it is reasonable to think that a substantial proportion of such cases have led to publication. A compilation of published case reports and series of flow diversion for posterior circulation aneurysms may, therefore, be a reasonable reflection of the overall population. This is supported by our meta-analysis (Fig 3), which shows similar findings in our series compared with prior large series of a similar patient population. Second, FD use has evolved across time with different generations of devices and increasing experience and skill— factors that could not be analyzed with our study design. Finally, antiplatelet therapy is a critical component of flow diversion. Antiplatelet responsiveness has been associated with complications in flow diversion of cerebral aneurysms— nonresponsiveness is associated with thrombotic complications, while hyper-responsiveness is associated with hemorrhagic complications.³¹ This association has also been specifically demonstrated with flow diversion of posterior circulation aneurysms.¹⁴ Unfortunately, our study design did not allow uniform assessment of antiplatelet management. This critical factor, however, warrants further study.