Elsevier

World Neurosurgery

Volume 115, July 2018, Pages e200-e205
World Neurosurgery

Original Article
Outcomes After Off-Label Use of the Pipeline Embolization Device for Intracranial Aneurysms: A Multicenter Cohort Study

https://doi.org/10.1016/j.wneu.2018.04.012Get rights and content

Highlights

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    Off-label use of PED is not fully established.

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    Clinical and angiographic outcomes of off-label use of PED were examined.

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    Complications associated with off-label use of PED were also examined.

Objective

To examine outcomes of Pipeline embolization device (PED) use for treatment of intracranial aneurysms outside of U.S. Food and Drug Administration–approved indications.

Methods

Data from patients with aneurysms treated with off-label use of PED were pooled from 4 centers in a retrospective multicenter cohort study. Primary endpoints were decline in modified Rankin Scale score by at least 1 point and angiographic aneurysm occlusion at follow-up.

Results

The study cohort comprised 109 patients. Mean aneurysm size was 8.4 ± 7.4 mm, 20.2% of aneurysms were located in the posterior circulation, and 11.9% of aneurysms were ruptured. The most common reasons for off-label use were aneurysm size (50.5%), aneurysm location (25.7%), and both size and location (10.1%). Mean follow-up was 9 months. Complete occlusion was achieved in 82.5% of cases at last angiographic follow-up. Modified Rankin Scale score decline was found in 18.8% of cases. On univariate analysis, age, aneurysm size, aneurysm morphology, aneurysm location, reason for off-label use, and rupture status were not associated with clinical decline or aneurysm occlusion on angiography. On multivariate analysis, treatment of a ruptured aneurysm with PED was found to be an independent predictor of postoperative decline in modified Rankin Scale score, and size as the only reason for off-label PED use was found to be an independent predictor of complete occlusion on final angiography.

Conclusions

Off-label use of PED has a reasonable risk-to-benefit profile for appropriately selected aneurysms. Posterior circulation location and fusiform morphology do not appear to be associated with worse clinical or angiographic outcomes.

Introduction

The Pipeline embolization device (PED) (Medtronic, Minneapolis, Minnesota, USA) was developed to treat large, wide-necked intracranial aneurysms.1, 2, 3 In 2011, the U.S. Food and Drug Administration (FDA) specifically approved PED for the treatment of adults (≥22 years old) with large (diameter ≥10 mm) or giant (diameter ≥25 mm), wide-necked (≥4 mm or no discernible neck) saccular aneurysms arising from petrous to superior hypophyseal segments of the internal carotid artery (ICA). The long-term clinical and angiographic outcomes of PUFS (Pipeline for Uncoilable or Failed Aneurysms) showed that PED is safe and effective for large and giant wide-necked aneurysms of the ICA. At the 5-year follow-up of PUFS, complete occlusion occurred in 90.6% of the aneurysms treated with PED.2 Several case series have also reported favorable results treating similar aneurysms with PED.3, 4, 5 Despite limited supportive data, the use of PED for indications not specified in the original FDA approval has become increasingly widespread.6, 7 Particularly common off-label uses of PED include treatment of aneurysms with previous stent-assisted coiling, ruptured aneurysms, small or medium-sized (diameter <10 mm) aneurysms, distal circulation aneurysms, posterior circulation aneurysms, fusiform aneurysms, pseudoaneurysms, and carotid-cavernous fistulas.8

Although the safety of PED has been reported, several studies highlighted some significant complications that can occur with this procedure.9, 10, 11 Possible devastating outcomes associated with the off-label use of PED (i.e., the use of PED for indications not approved by the FDA), including unexpected intraparenchymal hemorrhage, perforator infarction, postoperative aneurysm rupture, and death, have not been rigorously investigated. Owing to the limited and conflicting data, questions remain about the safety and efficacy of off-label use of PED. In this article, we report our experience with the off-label use of PED in treating intracranial aneurysms at 4 neurovascular centers.

Section snippets

Materials and Methods

We conducted a retrospective analysis on a prospectively collected database of patients whose intracranial aneurysms were treated with PED outside the FDA-approved indications between 2011 and 2015. The data were collected from 4 well-known neurovascular centers at different institutions. Each center reviewed its own radiographic images and entered data into a combined database. Institutional review board approval for use of patients' retrospective data was obtained separately from each

Baseline Characteristics

The data of 109 patients were included (83.5% women and 16.5% men). Mean patient age was 54.4 ± 12.3 years. The mean size of the aneurysm was 8.36 ± 7.36 mm. Table 1 summarizes the reasons for off-label usage. The most common reasons for off-label use were aneurysm size <10 mm (50.5%), aneurysm location (25.7%), and a combination of both size <10 mm and location (10.1%). Table 2 summarizes the aneurysm locations. The most common location of the aneurysms was in the ICA-ophthalmic segment

Discussion

Flow diverter devices have been gaining popularity in the treatment of intracranial aneurysms. Several studies have shown that their use is feasible and effective for unruptured aneurysms with complex anatomy, for which coiling or surgical intervention could be challenging.13, 14, 15, 16 Variable rates of aneurysm occlusion and complications have been reported in the literature. Brinjikji et al.10 conducted a meta-analysis that included 29 studies of flow diversion for aneurysms. The

Conclusions

Off-label use of PED has a favorable risk-to-benefit profile for appropriately selected aneurysms. Although patient selection is likely to be a major factor in achieving acceptable results with this technology, posterior circulation and fusiform aneurysms do not appear to be associated with worse clinical or angiographic outcomes. The treatment of ruptured aneurysms with PED may be a reasonable option in some cases. However, the potential adverse effects of dual antiplatelet therapy in the

References (26)

  • I. Arrese et al.

    Flow-diverter devices for intracranial aneurysms: systematic review and meta-analysis

    Neurosurgery

    (2013)
  • T. Becske et al.

    Long-term clinical and angiographic outcomes following Pipeline embolization device treatment of complex internal carotid artery aneurysms: five-year results of the Pipeline for Uncoilable or Failed Aneurysms Trial

    Neurosurgery

    (2017)
  • D.F. Kallmes et al.

    International retrospective study of the Pipeline embolization device: a multicenter aneurysm treatment study

    AJNR Am J Neuroradiol

    (2015)
  • T. Becske et al.

    Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial

    Radiology

    (2013)
  • G.K. Wong et al.

    Flow diverters for treatment of intracranial aneurysms: current status and ongoing clinical trials

    J Clin Neurosci

    (2011)
  • F.C. Albuquerque et al.

    A reappraisal of the Pipeline embolization device for the treatment of posterior circulation aneurysms

    J Neurointerv Surg

    (2015)
  • N. Chalouhi et al.

    Treatment of posterior circulation aneurysms with the Pipeline embolization device

    Neurosurgery

    (2013)
  • S.B. Murthy et al.

    Treatment of intracranial aneurysms with Pipeline embolization device: newer applications and technical advances

    Curr Treat Options Neurol

    (2016)
  • F. Briganti et al.

    Italian multicenter experience with flow-diverter devices for intracranial unruptured aneurysm treatment with periprocedural complications—a retrospective data analysis

    Neuroradiology

    (2012)
  • W. Brinjikji et al.

    Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis

    Stroke

    (2013)
  • T.E. Darsaut et al.

    Aneurysm rupture after endovascular flow diversion: the possible role of persistent flows through the transition zone associated with device deformation

    Interv Neuroradiol

    (2013)
  • D. Roy et al.

    Endovascular treatment of unruptured aneurysms

    Stroke

    (2001)
  • F. Briganti et al.

    Endovascular treatment of cerebral aneurysms using flow-diverter devices: a systematic review

    Neuroradiol J

    (2015)

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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