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Abstract
Background The Pipeline Vantage Embolization Device (PEDV) is the fourth-generation pipeline flow diverter for intracranial aneurysm treatment. There are no outcome studies for the second PEDV version. We aimed to evaluate safety and efficacy outcomes. Primary and secondary objectives were to determine outcomes for unruptured and ruptured cohorts, respectively.
Methods In this multicenter retrospective and prospective study, we analyzed outcome data from eight centers using core laboratory assessments. We determined 30-day and ≥3-month mortality and morbidity rates, and 6- and 18-month radiographic aneurysm occlusion rates for procedures performed during the period July 2021–March 2023.
Results We included 121 consecutive patients with 131 aneurysms. The adequate occlusion rate for the unruptured cohort at short-term and medium-term follow up, and also for the ruptured cohort at short-term follow up, was >90%. Two aneurysms (1.5%) underwent retreatment. When mortality attributed to a palliative case in the unruptured cohort, or subarachnoid hemorrhage in the ruptured cohort, was excluded then the overall major adverse event rate in respective cohorts was 7.5% and 23.5%, with 0% mortality rates for each. When all event causes were included on an intention-to-treat basis, the major adverse event rates in respective cohorts were 8.3% and 40.9%, with 0.9% and 22.7% mortality rates.
Conclusions For unruptured aneurysm treatment, the second PEDV version appears to have a superior efficacy and similar safety profile to previous-generation PEDs. These are acceptable outcomes in this pragmatic and non-industry-sponsored study. Analysis of ruptured aneurysm outcomes is limited by cohort size. Further prospective studies, particularly for ruptured aneurysms, are needed.
- Aneurysm
- Flow Diverter
- Hemorrhage
- Subarachnoid
- Intervention
Data availability statement
Data are available upon reasonable request but UK HRA/REC compliance is needed.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
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What is already known on this topic
There are no published outcome studies for the globally-released second version of the Pipeline Vantage Embolization Device (PEDV) which has superseded the first version that was released to only a few testing centers.
What this study adds
For unruptured aneurysm treatment, the second PEDV version appears to have a superior efficacy (radiological occlusion rate) and similar safety profile to previous-generation Pipeline Embolization Devices. For the treatment of ruptured aneurysms, conclusions are limited due to the cohort size; however, observations are that efficacy appears similar to previous studies and may be acceptable, but that there appears to be a high rate of adverse events.
How this study might affect research, practice or policy
Overall, these are acceptable outcomes for unruptured aneurysm treatment in this pragmatic and non-industry-sponsored study. To justify the routine use of PEDVs for ruptured aneurysms, evidence from further prospective outcome studies is needed.
Introduction
For more than a decade, there has been a steady increase in the indications for use of flow diverter devices in the treatment of aneurysms.1 The first-generation Pipeline Embolization Devices (PEDs) were used increasingly following their introduction in 2011 with proven safety and efficacy (radiological occlusion rates).2 3 The second-generation (Pipeline Flex Embolization Device) improved the ability to reposition and redeploy the PED,4 while the third-generation (PED with Shield Technology) was coated with phosphorylcholine in order to reduce stent thrombogenicity and had similar efficacy (occlusion rates) and safety outcomes compared with previous generations.5 6 Further refinements resulted in the latest (fourth) generation (Pipeline Vantage Embolization Device (PEDV)) and aimed to improve delivery, distal opening, wall apposition, and ease of re-sheathing.7 8 The first limited-release version of PEDV was discontinued following deployment difficulties7 and replaced by a second version which is now the only commercially available PED (online supplementary fig. S1). Our study aim was to assess short-term and medium-term safety and efficacy (occlusion rates) outcomes of the second version. The primary and secondary objectives were to determine these outcomes for unruptured and ruptured cohorts, respectively.
Supplemental material
Methods
A multicenter, pragmatic study was performed in eight UK centers from July 2021 to March 2023. The inclusion criteria were all patients ≥18 years old who underwent PEDV aneurysm treatment. Centers used local protocols for patient selection, treatment, and follow up. We captured consecutive prospective clinical and radiological follow-up data. We also captured consecutive retrospective treatment data with details including multidisciplinary team make-up, population at risk, procedural details, and anticoagulation and antiplatelet protocols. The study was performed in accordance with the 1964 Declaration of Helsinki and later amendments (UK Research Ethics Committee and Health Research Authority IRAS 317314).
Study endpoints
The primary safety endpoint was the cumulative occurrence of major adverse events at all follow-up timepoints. The primary efficacy endpoint was adequate occlusion at short-term, 6-month (range 3–9 months) follow up. The secondary efficacy endpoint was adequate occlusion at medium-term, 18-month (12-30) follow up. Further definitions are provided below.
Patient details
Data collected included age at presentation and gender. In the ruptured aneurysm cohort, the Hunt and Hess scale was used to assess the pre-operative clinical state of the patient.
Aneurysm details
We collected detailed data on rupture status, previous treatment, location, size, and morphology. Data included aneurysm type (true or pseudoaneurysm), shape (saccular, fusiform, or blister), smooth or irregular (lobulated/daughter sac), whether located in sidewall or bifurcation, and whether thrombosed. Aneurysm measurements included neck, dome width, height, and maximum diameter. Dome-to-neck, width-to-height, and aspect ratios were calculated for all aneurysms. Details were similarly collected for any secondary (non-target) aneurysms treated by the same PEDV during the same session.
Procedure details
We recorded access routes (radial or femoral), catheters used, data on device deployment failure, and adjuncts used (eg, coiling or balloon angioplasty). O’Kelly Marotta scaling (OKM) was determined immediately after PEDV deployment.9
Adverse events
Adverse events were classified according to International Retrospective Study of the Pipeline Embolization Device (IntrePED) methodology.10 “Neurologic adverse events” included subarachnoid hemorrhage (SAH), intraparenchymal hemorrhage, ischemic stroke, parent artery stenosis, and cranial neuropathy. Complications were considered “peri-procedural” if occurring <30 days after embolization and “post-procedural” if occurring ≥30 days. A persistent clinical deficit at 7 days following the event was defined as a “major” adverse event. Other events that resolved within 7 days with no clinical sequelae were defined as “minor” adverse events.
Follow-up imaging
Digital subtraction angiography (DSA), computed tomography angiography (CTA), and magnetic resonance angiography (MRA) were used alone or in combination according to local center protocol. Follow-up imaging was performed at short- and medium-term. A Modified Raymond Roy Classification (MRRC) scale of I or II was considered “adequate occlusion”; and IIIa or IIIb “inadequate occlusion” (online supplementary fig. S2).11 OKM was used additionally in cases with follow-up DSA. In-stent stenosis and patency of aneurysmal arterial branches were assessed. In-stent stenosis was graded as 0%, <50% stenosis, or ≥50% stenosis. Cross-sectional imaging allowed longitudinal axial aneurysmal size comparisons,12 and interval increases were recorded with a threshold of >2 mm. Retreatment rates were determined.
Statistical analysis
Both core laboratory and local reader outcome assessments were made for each case. Inter-rater reliability was determined using weighted Cohen’s kappa.13 For all discrepant readings, core laboratory assessments were used. Outcomes were calculated on both a complete per-protocol basis (device deployed and followed up) and an intention-to-treat (ITT) basis (included device not deployed or patient deceased before follow up). Aneurysm characteristics and occlusion rates were performed on a per-aneurysm basis because some patients had >1 aneurysm treated with ≥1 PEDV. Fisher exact tests (and the Freeman–Halton extension) were employed for comparative statistics. Descriptive and comparative statistics were calculated using SPSS (IBM Version 26.0).
Results
Eight centers were included in the study (six in England, one in Scotland, and one in Wales) with a mean population-at-risk of 2.25 million per center catchment area. All cases were selected following consensus at local neurovascular multidisciplinary team meetings which included senior (UK consultant grade; US attending equivalent) interventional neuroradiologists (median three per center) and neurovascular surgeons (median two per center). The operators had 9.1±5.9 years (mean±SD; range 2–25 years) of experience.
Patients and aneurysm characteristics
The unruptured cohort included 108 patients with 116 aneurysms on an ITT basis. The PEDV could not be deployed safely in 3/108 (2.8%) patients with 4/116 (3.4%) aneurysms. One terminally-ill patient 1/108 (0.9%) palliated for a partially thrombosed fusiform basilar artery giant aneurysm died within the peri-procedural time window before follow-up imaging, giving 104 patients with 111 aneurysms for complete per-protocol analysis (table 1). The ruptured cohort included 22 patients with 25 aneurysms on an ITT basis, with 17 patients with 20 aneurysms available for complete per-protocol analysis. In this cohort, 5 patients with five aneurysms died from SAH complications within the peri-procedural time window before follow-up imaging. Of all the patients treated with PEDV, 37/121 (30.6%) were retreatments (36 previous endovascular procedures (coiling, intrasaccular device implantation, stenting), 1 open surgery (wrapping)). Single aneurysms were treated in 111/121 (91.7%) procedures, and two aneurysms were treated in 10/121 (8.3%) procedures.
Patient and aneurysm characteristics (per-protocol analysis)
Antiplatelets and anticoagulation
Regimens varied between center pre- and post-treatment (online supplemental table S1). Four centers (50%) routinely performed platelet resistance testing using VerifyNow (Accriva Diagnostics, San Diego, CA, USA). One center (12.5%) performed testing only when clopidogrel was used.
Treatment
Interventional approaches and catheter details are summarized in online supplemental table S2. The most common guide catheter for a transfemoral approach was the Neuron MAX (Penumbra, Alameda, CA, USA) and for a transradial approach the Benchmark (Penumbra). Implanted PEDV sizes ranged from 2.5×10 to 6.0×50 mm. Adjunctive coiling was performed in 41/121 (33.9%) patients. In-stent balloon angioplasty was performed in 20/121 (16.6%) patients. Two patients (1.7%) underwent adjunctive Woven EndoBridge (WEB) (MicroVention, Aliso Viejo, CA, USA) implantation. Immediate postinterventional occlusion rates are shown in online supplemental table S3.
Clinical outcomes
Six patients (6/130, 4.6%) died in the peri-procedural period on an ITT basis (5/6, 83.3% from presenting SAH). All surviving patients (124/124) had a minimum of ≥3 months clinical follow up of which 88/124 (71.0%) had ≥6 months follow up (online supplemental table S4).
Safety endpoints
The primary safety endpoint (cumulative major adverse event rate) was 8.3% (9/108) patients with unruptured aneurysms on an ITT basis (table 2). The mortality rate was 0.9% (1/108) on an ITT basis. All major adverse events were neurological. There was one major adverse event ≥3 months and no adverse events ≥6 months. On a per-protocol basis, the cumulative major adverse event rate was 7.7% (8/104) and the mortality rate was 0% (detailed below); if the three patients requiring alternative treatment for failed PEDV deployment are added, the respective rates were 7.5% (8/107) and 0%.
Clinical outcomes (intention-to-treat analysis unless otherwise described)
Clinical outcomes for ruptured aneurysms were assessed as a secondary objective (table 2). The primary safety endpoint (cumulative major adverse event rate) was 9/22 (40.9%) patients on an ITT basis. The mortality rate was 5/22 (22.7%) on an ITT basis. All major adverse events were neurological, and there were no adverse events ≥30 days. On a per-protocol basis, the cumulative major adverse event rate was 23.5% (4/17) and mortality rate was 0% (detailed below).
Peri-procedural adverse events (without neurological sequelae)
PEDV deployment failure occurred only within the unruptured patient cohort (3/108, 2.8%) procedures (detailed in table 2, including subsequent endovascular treatments). Operators reported that PEDV deployment was challenging in 6/108 (5.6%) and 1/22 (4.5%) of unruptured and ruptured procedures, respectively, due to PEDV proximal migration, shortening, herniation into aneurysm, or improper sizing, or due to inadequate large catheter support. In all seven cases, the PEDV was deployed without clinical complication. Other adverse events without neurological sequelae were intraprocedural thrombi formation which were treated therapeutically, extracranial ICA dissections which did not appear to be stenotic and were treated therapeutically, and groin hematomas which were managed conservatively.
Peri-procedural neurological adverse events in the unruptured cohort
Seven patients (7/108, 6.5%) had ischemic strokes, two of which lasted more than 7 days and were categorized as major complications. Two patients (2/108, 1.9%) had cranial neuropathies. One in the form of horizontal diplopia which started on day 17 after the procedure and lasted for 10 days. The other had a right retinal branch artery occlusion presenting on day 7 after the procedure with right eye pain and persistent visual loss. Another patient had hemorrhagic transformation of an asymptomatic subcortical ischemic infarct on day 24 after the procedure. Clinical features resolved after 8 days and the patient was discharged. A patient who presented with worsening cognition, gait imbalance, and confusion due to a thrombosed fusiform basilar artery giant aneurysm underwent palliative stepwise Leo stent (Balt, Montmorency, France) placement followed by a subsequent PEDV and coiling procedure. The patient developed a fatal SAH 3 days after the final procedure. While adjudication concluded that imminent death was inevitable regardless of PEDV implantation in this terminally-ill patient,14 15 arguably the ITT-derived mortality rate better represents real-world use.
Post-procedural neurological adverse events in the unruptured cohort
Three patients (3/108, 2.8%) had ischemic strokes that resolved within 7 days. One patient had a cranial neuropathy on day 55 after the procedure presenting with headache and left temporal hemianopia which resolved with steroids after 14 days. One patient who underwent stent-within-stent deployment developed delayed asymptomatic occlusion of the left intracranial ICA diagnosed on imaging on day 64 after the procedure. One patient developed clinical features suggestive of meningitis 165 days after the procedure; however, cross-sectional imaging showed 10 mm enlargement of the thrombosed component of the aneurysm and mass effect. This was successfully managed with a reduction from dual to single antiplatelet therapy with a corresponding cessation of aneurysm growth and resolution of the surrounding edema.
Periprocedural neurological adverse events in the ruptured cohort
All complications in this cohort were peri-procedural. Five patients had a poor initial presentation (Hunt and Hess 4–5) and died shortly after the procedure. These cases were included on an ITT basis but excluded from per-protocol analyses as adjudication concluded that death was likely to be attributable to the presenting SAH without contribution from PEDV implantation. Four patients (4/23, 17.4%) developed ischemic stroke, three of which were categorized as major complications. Adjudication was inconclusive for the cause of the ischemic strokes and the data were not excluded from per-protocol analyses. One patient re-ruptured, developed hydrocephalus, and underwent extraventricular drain insertion (procedure and complication management detailed in table 2).
For all neurological events, unruptured and ruptured, we have shown the association between which antiplatelet therapy was used in these patients, and whether VerifyNow was employed (online supplemental table S5).
Follow-up imaging and aneurysm occlusion
There was variation in imaging follow-up protocols between centers (online supplemental table S6). DSA was used preferentially in some centers if the aneurysm had been coiled, or if in-stent stenosis was suspected but indeterminate on MRA due to susceptibility artefact. To determine the suitability of MRA for PEDV follow-up imaging, we also compared those follow-up DSAs (considered reference standard) and MRAs (considered index test) that were performed within 3 months of one another. Nine aneurysms from six centers (mean imaging interval 2.1 months) were included with perfect agreement (kappa=1.0) in MRRC assessments (time-of-flight and contrast-enhanced MRA were used eight times and once, respectively). Therefore, MRA was considered suitable for the estimation of accurate occlusion rates alongside DSA. When MRA and DSA were compared for in-stent stenosis assessment, there was a 6/9 (66.6%) discrepancy rate as MRA was considered uninterpretable due to susceptibility (online supplemental fig. S3); 2/9 (22.2%) patients demonstrated <50% stenosis on DSA but were uninterpretable on MRA. Therefore, MRA was not considered accurate for estimating in-stent stenosis.
Efficacy endpoints
Aneurysm occlusion
Short-term follow-up imaging (6 months) was available for 110/111 unruptured aneurysms. The primary efficacy endpoint was 100/110 (90.9%) aneurysms adequately occluded on a per-protocol basis (table 3). On an ITT basis, we classified the one aneurysm without short-term follow-up imaging as inadequately occluded, and we included the four aneurysms which failed flow diversion (all of which had available short-term follow-up imaging) to give 104/115 (90.4%) aneurysms that met the efficacy endpoint. The complete occlusion rate (MRRC 1) was 70.9% (78/110) and 71.3% (82/115) on a per-protocol and ITT basis, respectively.
Unruptured aneurysms imaging follow up (per-protocol analysis).
Medium-term follow-up imaging (18 months) was available for 13/111 unruptured aneurysms (including the one aneurysm without short-term follow-up imaging). The secondary efficacy endpoint was 12/13 (92.3%) aneurysms adequately occluded on a per-protocol basis (table 3). The complete occlusion rate (MRRC 1) was 10/13 (76.9%) on a per-protocol basis (no additional ITT cases). Of the 12/13 aneurysms that could be compared longitudinally between the two follow-up timepoints, 10/12 (83.3%) aneurysms were stable and 2/12 (16.7%) improved from MRRC 2 to MRRC 1.
Short-term follow-up imaging for 20/20 ruptured aneurysms was assessed as a secondary objective. The primary efficacy endpoint was 18/20 (90.0%) aneurysms adequately occluded on a per-protocol basis (table 4). The complete occlusion rate (MRRC 1) was 80% (16/20). There was no medium-term follow-up imaging.
Ruptured aneurysm imaging follow up (per-protocol analysis)
Sac branch remodeling and in-stent stenosis
Of the 26/131 aneurysms (19.8%) that had arterial branches originating from the aneurysm sac, no branch was reduced in caliber at follow up and adequate occlusion was seen in 88.5% (23/26). In-stent stenosis rates are confounded but included for completeness (online supplemental table S7).
Aneurysm size increase
Longitudinal cross-sectional imaging was available to determine interval changes in axial diameter in 100/111 (90.1%) and 17/20 (85.0%) unruptured and ruptured aneurysms at short-term follow up, respectively. An increase in size was seen in 5/100 (5.0%) and 1/17 (5.9%) aneurysms, respectively (online supplemental table S8). At medium-term follow up, 5/13 (38.5%) unruptured aneurysms had longitudinal cross-sectional imaging and no increase in size was seen.
Retreatment
Two aneurysms (2/131, 1.5%) underwent further flow diversion for a remnant and an enlargement, respectively (detailed in table 3 and online supplemental table S8).
Subgroup analyses
A subsequent publication will present subgroup analyses including center heterogeneity; however, some initial observations were included (online supplemental table S9) after we examined the relationship between occlusion rates and (1) sidewall/bifurcation aneurysm location, (2) aneurysm neck size, and (3) aneurysm size. We found that adequate occlusion was associated with narrow-neck aneurysms at short-term follow up in the ruptured cohort.
Discussion
Principal findings
The adequate occlusion rate for the unruptured cohort at short-term and medium-term follow up, and also for the ruptured cohort at short-term follow up, was >90% regardless of whether analysis was on an ITT or per-protocol basis.
The major adverse event rate inevitably differed according to our analysis method: when mortality attributed to a palliative case in the unruptured cohort, or to SAH in the ruptured cohort, is excluded then the overall major adverse event rate in respective cohorts was 7.5% and 23.5%, with a 0% mortality rate for both. When all event causes are included on an ITT basis, the major adverse event rates in respective cohorts were 8.3% and 40.9%, with a 0.9% and 22.7% mortality rate.
Comparison with studies worldwide
There were technical difficulties in 24.6% of treatments using first-version PEDVs of which 19.3% were due to stent ‘hang up’ on the pusher wire during deployment.7 In our study of second-version PEDVs, technical difficulties were encountered in 8.3% and 4.5% of the unruptured and ruptured cohorts respectively, plausibly demonstrating deployment improvements of the redesigned PEDV. In contrast to the 2.8% of second-version PEDVs which failed to deploy in the unruptured aneurysm cohort (0% in the ruptured cohort), all first-version PEDVs were deployed eventually in the earlier study, although not all were optimally placed due to deployment difficulty.7 This second-version PEDV deployment failure rate appeared to be similar to the previous generation of PEDs with Shield Technology (2.0–2.2%).5 6
Unruptured cohort
For our primary objective (treatment efficacy in unruptured aneurysms), the primary efficacy endpoint (adequate occlusion at short-term follow up) appeared higher than the previous generation of PEDs with Shield Technology when pragmatic and ITT methodology was employed using similar follow-up timepoints.6 Here, the adequate occlusion rates for the two studies were 90.4% and 78.8% at short-term and 92.3% and 90.3% at medium-term, respectively. The complete occlusion rates for the two studies were 71.3% and 69.2% at short-term and 76.9% and 82.7% at medium-term, respectively. When also compared with a large, single-center registry of 1000 aneurysms treated by PED, the PEDESTRIAN study, our medium-term adequate occlusion rates appeared higher (92.3% and 80.2%) and complete occlusion rates appeared comparable (76.9% and 75.8%).16 The short-term efficacy of first-version PEDVs, where 5% ruptured aneurysms were included, was 95.5% and 77.9% for adequate and complete occlusions, respectively.7
For our primary objective (treatment safety in unruptured aneurysms), the primary safety endpoint (cumulative occurrence of major adverse events at follow up) appeared similar to that seen in a pragmatic study of earlier-generation PEDs using a similar short-term follow-up timepoint and a similar adverse event classification system.3 Here, the major adverse event rates for the two studies were 8.3% and 6.8%, respectively. For comparison, major adverse event rates using the same classification but longer follow up in previous generation PEDs ranged from 7.4% to 13.3%.6 10 12 The short-term safety of first-version PEDVs, which appeared to use a different classification system, appeared to have a major adverse event rate of 4.8% on an ITT basis.7 The first and second PEDV version studies showed a 1.7% and 0.9% mortality rate, respectively. Both study rates were 0% on a per-protocol basis, which compares with 1.6–3.3% in the previous-generation PED studies described earlier.3 6 10 12
Ruptured cohort
For our secondary objective (treatment efficacy in ruptured aneurysms), the primary efficacy endpoint (adequate occlusion at short-term follow up) appeared higher than that seen in a study of previous-generation PEDs followed up at a similar timepoint and when applying pragmatic and ITT methodology.17 Here, the adequate occlusion rates for the two studies were 90.0% and 80.8% at short term, respectively. The complete occlusion rates for the two studies were 80.0% and 69.2%, respectively. When a range of follow up and study methodology was combined in a pooled analysis of 12 studies comprising 145 patients, the complete occlusion rate was similar to our study at 87.5%.18
The primary safety endpoint (cumulative occurrence of major adverse events at follow up) is difficult to compare directly with previous PED studies due to different and/or unclear morbidity classifications. The estimated major adverse event rate was 26.9% (7/26)17 and 16.5% (23/145)18 in the aforementioned similar study and pooled analysis, respectively. In contrast, the major adverse event rate in our study was 40.9% and 23.5% on an ITT and per-protocol basis, respectively. One adverse event was a re-rupture (1/20, 5%) in our study which compares to 2.1%17 and 3.8%18 in the respective publications mentioned previously. The mortality rate was 11.5%17 and 7.9%18 in the respective publications, and 10.5% in the IntrePED ruptured subgroup.10 In comparison, the mortality rate in our study was 22.7% and 0% on an ITT (including death from SAH) and per-protocol basis, respectively.
Strengths and limitations
To the best of our knowledge, this was the first pragmatic, non-industry-sponsored study of the second PEDV version. We gave a range of outcomes on a per-protocol and ITT basis that will allow comparison with a wide range of studies.
Nonetheless, the study has several limitations. Our additional analyses demonstrated that MRA was suitable for aneurysm occlusion but not in-stent stenosis assessment. However, the number of cases used for these assessments were small. Second, while the prospective follow-up data are considered reliable, the retrospective treatment data are considered less reliable. Third, while outcomes were captured comprehensively in the short term for both adverse event and imaging follow up, there were limited outcome data for longer-term follow up. It is noteworthy, however, that there is a known rapid reduction in the likelihood of adverse events following previous-generation PED procedures,3 6 19 20 and in the current study no adverse events were seen ≥6 months. Furthermore, previous generations of PEDs demonstrate increased adequate and complete occlusion rates over time,6 19 20 a finding also noted in the current study. Fourth, while similar in size to other relevant studies of ruptured aneurysms,18 it is unclear how data relating to this secondary objective compare to other studies given methodological heterogeneity and a dataset enriched with small (60%) and blister (15%) aneurysms. Fifth, one drawback of a pragmatic study design is the lack of a standardized follow-up imaging protocol. While we showed that MRA appeared suitable for aneurysm occlusion assessment and therefore equivalent to DSA, there was a range of timings within our short-term and mid-term definitions limiting direct comparison with any studies with a standardized follow-up imaging protocol using ranges which are narrower.
Conclusions
There are no published outcome studies for the second PEDV version which has superseded the limited-release first version. The second version appears easier to deploy compared with the first version. For unruptured aneurysm treatment, the second version appears to have a superior efficacy and similar safety profile to previous-generation PEDs. Overall, these are acceptable outcomes in this pragmatic and non-industry-sponsored study. Analysis of ruptured aneurysm outcomes is limited by cohort size. While efficacy appears similar to previous studies and may be acceptable, there appears to be a high rate of adverse events. To justify the routine use of PEDVs for ruptured aneurysms, evidence from further prospective outcome studies is needed.
Data availability statement
Data are available upon reasonable request but UK HRA/REC compliance is needed.
Ethics statements
Patient consent for publication
Ethics approval
This study involved human participants and was approved by UK Research Ethics Committee and Health Research Authority IRAS 317314 (https://classic.clinicaltrials.gov/ct2/show/record/NCT05626504). Participants gave informed consent to participate in the study before taking part.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
TCB and AB are joint first authors.
AM and AS are joint senior authors.
Twitter @ThomasCBooth
Contributors TCB designed data collection tools, monitored data collection for the whole trial, wrote the statistical analysis plan and analyzed the data, and drafted and revised the paper; he is also guarantor. ABa collected, cleaned, curated, and analyzed the data and drafted the paper. JL, HS, ABl, AI, TM, JB, APN, TP, FII, NK, PB, SS, JS, DW, CT, AK-V, AAS, MAE-L, AM, and AS collected, cleaned, and curated data and revised the paper. All authors approved the final version of the paper.
Funding This study was funded by the Wellcome Trust (WT 203148/Z/16/Z) and the Egyptian Cultural and Educational Bureau (NMJ3/20).
Competing interests Microvention core laboratory for neurointerventional study: payment to TCB. Siemens Healthineers Speakers Bureau Educational lecture on brain tumours, not related to aneurysms: payment to TCB. Medtronic Speakers Bureau Educational lecture on an independent non-industry-sponsored study published in AJNR 2019 on Pipeline Flow Diverter device: payment to TCB. Bayer Speakers Bureau Educational lecture on Explainability in AI, not related to aneurysms: payment to TCB. Consulting and proctoring agreement with Medtronic, Stryker, Balt, and Cerenovus: payment to TP. Microvention, Balt, and Medtronic support to attend meetings: payment to TM.
Provenance and peer review Not commissioned; externally peer reviewed.
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