The endovascular treatment of intracranial aneurysms using the Pipeline Embolization Device (PED; Medtronic) has been deemed safe and effective following a study involving data on 1,000 aneurysms from a single-centre registry. The study, the findings of which are published in the research journal Neurosurgery, found high rates of long-term complete aneurysm occlusion, stable or improved functional outcomes, and low rates of both complications and mortality.
“The PED is the most extensively investigated FD [flow diverter] available on the market,” the study’s researchers, Ivan Lylyk (Department of Interventional Neuroradiology and Neurosurgery, Instituto Médico ENERI-Clínica La Sagrada Familia, Buenos Aires, Argentina) and colleagues, write. “Initially, treatment with the PED was aimed principally at wide-necked and uncoilable aneurysms located in the anterior circulation below the internal carotid artery (ICA) bifurcation.
“As experience with PED grew and the technology matured, its use has expanded to include less complex and posterior circulation aneurysms, along with a greater understanding of associated complications; however, long-term follow-up data on these new indications are limited. Here, we report the results of the Pipeline Embolization Devices for the treatment of intracranial aneurysms (PEDESTRIAN) registry. We report the clinical and radiographic results from 1,000 aneurysms of various size and morphology treated with the PED, including those patients with long-term follow-up (≥5 years).”
In their retrospective review of data from the PEDESTRIAN registry, Lylyk et al included patients with complex intracranial aneurysms treated using the PED between March 2006 and July 2019—including those with unfavourable anatomy and/or recurrence following previous treatment, but excluding those with acute subarachnoid haemorrhage. These criteria saw a total of 835 patients (mean age=55.9±14.7 years; 80.4% female) with 1,000 aneurysms included in the review, who were assessed via the primary angiographic endpoint of complete occlusion and long-term stability. Clinical and radiological follow-up was performed at three-to-six months, 12 months, and yearly thereafter.
In total, 1,214 PEDs were deployed, Lylyk et al report, with a single device being used in 84.2% (n=842), and two or fewer devices being used in 95.8% (n=958) of aneurysms. Adjunctive coiling was performed in 9.3% (n=93) of cases. Intraoperative technical complications occurred in 4.8% (n=48) of treated aneurysms, with incomplete wall apposition of the device requiring balloon angioplasty representing the majority of technical complications (3.3% [n=33]) seen across the patient cohort.
Follow-up catheter angiography was available for 87.4% (n=730) of patients—with 861 aneurysms—at a mean of 24.6±25 months. Twelve-month angiography using Raymond Roy Classification (RRC) revealed complete occlusion (RRC I) of 75.8% (588/776) of aneurysms, while 4.4% (34/776) had a residual neck (RRC II) and 19.8% (154/776) showed residual filling (RRC III). For the 323 patients for which intermediate angiographic follow-up data (from two-to-four years) was available, complete occlusion was observed in 92.9%, and this improved further to 96.4% of patients (159/165) in delayed angiography (beyond five years). On logistic regression, Lylyk et al write that factors influencing 12-month complete aneurysm occlusion were age, male sex and hypertension.
Retreatment was required in 4% (n=40) of aneurysms, of which 92.5% (37/40) involved implanting another FD device, they add. Meanwhile, regarding clinical results, modified Rankin Scale (mRS) scores remained stable or improved in 96.2% (n=803) of patients in the periprocedural period (≤30 days), increasing to 99.1% (n=828) in the longer term (≤5 years), with multivariate analysis identifying age and non-saccular aneurysm morphology as independent predictors of mRS scores worsening. Because of this, Lylyk et al conclude: “Clinical and angiographic outcomes progressively improved over long-term follow-up, demonstrating intracranial aneurysm treatment with PED is safe and effective in a large cohort of aneurysms.”
Stroke-related complications occurred in 3.6% (n=30) of patients—with the majority of these cases being caused by in-stent thrombosis (2.5% [n=21])—and nine deaths occurred due to stroke. “We found a trend towards lower rates of thromboembolic complications since the implementation of prasugrel,” the authors add, reporting that 26 (4.4%) patients on the antiplatelet medication clopidogrel developed stroke compared with four (1.6%) patients on prasugrel. Haemorrhagic complications occurred in 1.8% (n=15) of patients, resulting in 11 deaths. The overall morbidity rate, including from subarachnoid haemorrhage, was 2.7% (n=23) and the all-cause mortality rate was 4.6% (n=38) across the entire patient cohort, while only aneurysm size was found to be a significant predictor of neurological death when assessed using Cox logistic regression.
In their report, Lylyk et al also draw comparisons between their review of the PEDESTRIAN registry, and previous studies of the PED in treating intracranial aneurysms—most notably the IntrePED (International retrospective study of Pipeline Embolization Device) study, which analysed 793 patients from 17 centres around the world, and saw multiple devices used in approximately twice as many aneurysms, as well as comparable mortality rates. The authors also discuss “comparable rates of long-term complete occlusion and complications…with a slightly higher rate of mortality” in the PEDESTRIAN registry compared to the multicentre, prospective, interventional single-arm PUFS (Pipeline for uncoilable or failed aneurysms) trial involving 108 patients, and “slightly lower rates of complete occlusion at six months and one year” compared to the prospective, international, multicentre postmarket ASPIRe (Aneurysm study of pipeline in an observational registry) study—along with similar rates of major morbidity and neurological mortality.
“Our study has several limitations inherent to the retrospective, single-centre design of data analysis, which may limit generalisability of the data, as well as the lack of core lab adjudication,” Lylyk and colleagues add. In spite of this, Lylyk told NeuroNews that, with up to 13 years of follow-up for the first cases in the PEDESTRIAN registry, this series demonstrates “for the first time” that PEDs are safe and effective “in the very long run”.
