PREMIER
Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification
Clinical Question
What are the long-term (3-year) safety and efficacy outcomes of the Pipeline Embolization Device (PED) for the treatment of small- and medium-sized, wide-necked, unruptured intracranial aneurysms?
Bottom Line
At 3 years, the Pipeline Embolization Device (PED) showed high rates of aneurysm occlusion and a low incidence of major neurological events, with no cases of aneurysm rupture, confirming its long-term safety and efficacy in small and medium unruptured intracranial aneurysms.
Major Points
- PREMIER is a prospective, single-arm, multicenter trial evaluating the PED in 141 patients with unruptured wide-necked aneurysms ≤12 mm.
- The primary effectiveness endpoint (complete aneurysm occlusion without significant stenosis or retreatment) was achieved in 78.3% at 3 years.
- Complete aneurysm occlusion (Raymond–Roy 1) at 3 years was 83.3%.
- Modified Cekirge–Saatci classification (mCSC) identified a 97.1% success rate including occlusion, neck remnant, or size reduction.
- The primary safety endpoint (major stroke or neurologic death) occurred in 2.8% over 3 years.
- There were no cases of delayed aneurysm rupture.
- Functional independence (mRS ≤2) was maintained in 97.7% of patients at 3 years.
Design
Study Type: Prospective, single-arm, multicenter interventional study
Randomization:
Blinding: Not applicable; endpoints were independently monitored and adjudicated
Enrollment Period: July 2014 to November 2015
Follow-up Duration: 3 years
Centers: 23
Countries: USA, Canada, Hungary, Switzerland
Sample Size: 141
Analysis: Two-sided 95% exact binomial test, last observation carried forward for imputation, logistic regression; performed using R and SAS
Inclusion Criteria
- Unruptured, wide-necked intracranial aneurysms
- Aneurysm size ≤12 mm
- Location in ICA (up to terminus) or vertebral artery (up to and including PICA origin)
Exclusion Criteria
- Clopidogrel resistance
- Full exclusion criteria reported in prior publication
Arms
| Field | Pipeline Embolization Device (PED) |
|---|---|
| Intervention | Treatment with the PED for unruptured wide-necked aneurysms ≤12 mm, followed by dual antiplatelet therapy guided by antiplatelet response testing |
| Duration | 3 years |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Complete aneurysm occlusion (Raymond–Roy 1) without significant parent artery stenosis (≤50%) or retreatment | Primary | 78.3% (108/138) | |||
| Complete aneurysm occlusion (Raymond–Roy 1) | Secondary | 83.3% (115/138) | |||
| Successful treatment per mCSC | Secondary | 97.1% | |||
| Functional independence (mRS ≤2) | Secondary | 97.7% (127/130) | |||
| Primary safety outcome (major stroke or neurologic death) | Adverse | 2.8% (4/140) | |||
| Aneurysm rupture | Adverse | 0% | |||
| Target aneurysm recurrence | Adverse | 0.7% (1/138) | |||
| Target aneurysm retreatment | Adverse | 5.0% (7/138) | |||
| Significant in-stent stenosis (>50%) | Adverse | 3.6% (5/138) |
Subgroup Analysis
Subgroup analysis at 3 years was not reported; prior 1-year analysis identified non-smoking and side branch presence as predictors of incomplete occlusion
Criticisms
- Single-arm design without a control group limits comparison with other treatments
- Long-term imaging follow-up not mandatory for completely occluded aneurysms after 1 year
- Results limited to small- and medium-sized unruptured aneurysms in specific anatomical locations
Funding
Medtronic, Inc.
Based on: PREMIER (Journal of NeuroInterventional Surgery, 2023)
Authors: Ricardo A Hanel, Gustavo M Cortez, Demetrius Klee Lopes, ..., David F Kallmes
Citation: J Neurointervent Surg 2023;15:248–254
Content summarized and formatted by NeuroTrials.ai.