we are updating metanalyis on the Population P: Adult patients present

we are updating metanalyis on the *Population (P):* Adult patients presenting with a transient ischemic attack (TIA) or non-disabling ischemic stroke caused by severe, symptomatic intracranial atherosclerotic stenosis (defined as 70%–99% baseline luminal narrowing via digital subtraction angiography). *Intervention (I):* Intracranial revascularization via Drug-Eluting Stent (DES) implantation. *Comparison (C):* Intracranial revascularization via conventional Bare-Metal Stents (BMS). *Outcomes (O):* Primary Safety: Combined rate of any stroke or all-cause mortality within 30 days post-procedure. Primary Efficacy: Radiographically confirmed In-Stent Restenosis (ISR, defined as 50% narrowing within or immediately adjacent to the stent struts) within 1 year. Secondary Performance: Target-vessel ischemic stroke recurrence within 12 months. help me write intorduction of this article

Running Command

mkdir -p /tmp/workspace/meta-analysis && cd /tmp/workspace/meta-analysis && unzip -o "/tmp/workspace/attachments/741fd62b-5925-481e-ba1b-756ee6393f07/drive-download-20260826T123234Z-1-001.zip" -d /tmp/workspace/meta-analysis/extracted && ls -la /tmp/workspace/meta-analysis/extracted

general-purpose

You are helping build the Introduction section of a meta-analysis comparing Drug-Eluting Stents (DES) vs Bare-Metal Stents (BMS) for intracranial revascularization in patients with symptomatic severe (70-99%) intracranial atherosclerotic stenosis (ICAS) presenting with TIA or non-disabling stroke. Outcomes of interest: 30-day stroke/death, 1-year in-stent restenosis (ISR), and 12-month target-vessel ischemic stroke recurrence. First read the PDF skill at /tmp/skills/pdf/SKILL.md to learn how to extract text from PDFs in this sandbox. Then extract and read the Introduction/Background/Discussion sections (skip methods/results tables) of these 9 PDF files located in /tmp/workspace/meta-analysis/extracted/: 1. "Shoraka 2025.pdf" 2. "song2012.pdf" 3. "GAUN 26.pdf" 4. "jia 2022.pdf" 5. "hassan 23.pdf" 6. "Lee 2013.pdf" 7. "Gottberg 2026.pdf" 8. "Ma 2025.pdf" 9. " Gong 24 old meta.pdf" (note leading space in filename) For EACH paper, identify and note: - Full citation (authors, year, journal if available) - Study type (RCT, cohort, meta-analysis, registry) - What it studied (DES vs BMS, or intracranial stenting in general) - Key background facts it cites (epidemiology of intracranial atherosclerotic disease, stroke recurrence rates, burden of ICAS-related stroke worldwide/in Asia, medical therapy trial results like SAMMPRIS, VISSIT, WEAVE/WOVEN, CASSISS) - Key findings relevant to DES vs BMS comparison (restenosis rates, periprocedural stroke/death rates, rationale for why DES might be superior - e.g. antiproliferative drug coating reducing neointimal hyperplasia, lower restenosis in coronary/peripheral literature) - Any stated gaps in evidence or limitations that justify a new meta-analysis on this topic Compile a structured, well-organized summary of ALL these findings organized by theme (not by paper), with inline citations (Author, Year) so I can synthesize a scientific Introduction section. Include specific numbers/statistics where available (e.g. restenosis rates %, stroke recurrence rates %, prevalence of ICAS as cause of stroke). Be thorough since this is the primary evidence base for the introduction. Return the full structured summary as your final answer - do not truncate it.

Searching PubMed

"intracranial atherosclerosis" AND "drug-eluting stent"

Searching the Web

drug-eluting stent vs bare-metal stent intracranial atherosclerotic stenosis meta-analysis restenosis

Reading File

Browsing Directory

~/meta-analysis/extracted/

Asking for Preferences

Which part of the Introduction evidence base should I extract and synthesize in full detail first?

give me the rationale of this metanalysis introduction

Reading File

Rationale

Symptomatic severe intracranial atherosclerotic stenosis (ICAS) is associated with a substantial risk of recurrent ischemic stroke, particularly among patients with recent transient ischemic attack or non-disabling stroke and 70%-99% luminal stenosis. Although aggressive medical treatment remains the foundation of management, endovascular revascularization continues to be considered in carefully selected patients with recurrent ischemia, impaired distal perfusion, or failure of medical therapy. However, the benefit of intracranial stenting is limited by periprocedural complications and by in-stent restenosis (ISR), a frequent late failure mechanism that may compromise vessel patency and contribute to recurrent target-territory ischemia.

Conventional bare-metal stents (BMS) provide mechanical luminal scaffolding but may provoke vascular injury, inflammation, and neointimal hyperplasia, thereby predisposing to ISR. Drug-eluting stents (DES), which release antiproliferative agents such as sirolimus or zotarolimus, were developed to reduce neointimal proliferation and have demonstrated lower restenosis rates in coronary and other vascular beds. Emerging intracranial data, including comparative observational studies and a randomized trial, suggest that DES may reduce angiographic ISR and possibly recurrent ischemic events without a clear increase in early stroke or mortality. Nevertheless, the available evidence is limited by small sample sizes, heterogeneous lesion characteristics and stent platforms, variable follow-up protocols, and inconsistent definitions and reporting of clinical outcomes.

Recent systematic reviews have generally suggested a restenosis advantage for DES over BMS, but the evidence base has expanded with newer comparative studies, including more contemporary stent technologies and patient cohorts. Moreover, prior reviews have not always been restricted to a clinically homogeneous population of adults with symptomatic, severe angiographically defined ICAS, nor have they consistently evaluated safety, angiographic efficacy, and target-vessel clinical recurrence using aligned time points. An updated meta-analysis is therefore needed to provide a focused estimate of the comparative safety of DES versus BMS at 30 days, their effectiveness in preventing radiographically confirmed ISR within 1 year, and their association with target-vessel ischemic stroke recurrence during 12 months of follow-up.

This review will help clarify whether the potential reduction in restenosis offered by DES translates into meaningful clinical benefit without compromising early procedural safety, thereby informing device selection and future trial design for patients undergoing intracranial revascularization.

now give the rationale

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Browsing Directory

~/

Searching PubMed

"intracranial atherosclerosis" AND "drug-eluting stent"

Searching the Web

drug-eluting versus bare-metal stents symptomatic intracranial atherosclerotic stenosis systematic review meta-analysis 2025

Browsing Directory

~/attachments/741fd62b-5925-481e-ba1b-756ee6393f07/

Reading Web Page

https://pmc.ncbi.nlm.nih.gov/articles/PMC11624788

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Finding Sources

Running Command

mkdir -p "/tmp/workspace/meta-analysis-update" && unzip -o "/tmp/workspace/attachments/741fd62b-5925-481e-ba1b-756ee6393f07/drive-download-20260829T144658Z-1-001.zip" -d "/tmp/workspace/meta-analysis-update/extracted" && python -c "from pathlib import Path; from pypdf import PdfReader; p=Path('/tmp/workspace/meta-analysis-update/extracted'); print('FILES:'); [print(x.name) for x in p.iterdir()]; print('\\n---FIRST PAGES---'); [print('\\n###',x.name,'\\n', (PdfReader(str(x)).pages[0].extract_text() or '')[:2500]) for x in p.glob('*.pdf')]"

Reading File

Rationale

Severe symptomatic intracranial atherosclerotic stenosis (ICAS) is a high-risk cause of recurrent ischemic stroke. For selected patients undergoing intracranial revascularization, maintaining durable vessel patency is a central concern because in-stent restenosis (ISR) can negate the initial angiographic result and may lead to recurrent ischemia in the treated vascular territory. Although bare-metal stents (BMS) provide immediate mechanical luminal expansion, vessel injury and subsequent neointimal hyperplasia may result in clinically important ISR.

Drug-eluting stents (DES) release antiproliferative agents intended to limit neointimal growth. Their use in intracranial lesions is therefore biologically appealing: DES may preserve luminal patency more effectively than BMS while maintaining similar procedural safety. The randomized trial by Jia et al. reported substantially lower 1-year ISR with DES than BMS (9.5% vs 30.2%) and fewer target-vessel ischemic stroke recurrences after the peri-procedural period, without a statistically clear difference in 30-day stroke or death. These findings support the hypothesis that the primary advantage of DES lies in durable angiographic efficacy rather than in reducing immediate procedural hazards.

However, the evidence remains difficult to translate into a definitive device-selection recommendation. Existing comparative studies differ in design, sample size, patient selection, lesion morphology and location, stent platforms and drug coatings, procedural techniques, antiplatelet regimens, imaging surveillance, and duration of follow-up. These differences may affect both restenosis detection and clinical event rates. In addition, ISR is an imaging-based outcome that may not consistently correspond to recurrent symptoms; conversely, clinical recurrence may arise from mechanisms other than restenosis. Safety, angiographic patency, and target-vessel stroke recurrence should therefore be evaluated separately at clinically relevant, prespecified time points.

Although recent systematic reviews have found that DES are associated with less ISR than BMS, the literature has continued to expand and published syntheses have varied in their eligibility criteria and outcome definitions. The 2024 Gong et al. meta-analysis and the 2025 Mirjani et al. meta-analysis support a potential restenosis benefit, but an updated review is justified if it incorporates newly available comparative evidence and applies a more homogeneous clinical question. In particular, restricting the population to adults with recent TIA or non-disabling ischemic stroke due to severe, symptomatic, angiographically confirmed 70%-99% ICAS reduces clinical heterogeneity and improves the direct relevance of the pooled estimates.

Accordingly, this updated meta-analysis will compare DES with conventional BMS using three complementary outcomes: (1) 30-day any-stroke or all-cause mortality as the primary safety outcome; (2) radiographically confirmed ISR within 1 year as the primary efficacy outcome; and (3) target-vessel ischemic stroke recurrence within 12 months as the key clinical performance outcome. This focused approach will clarify whether a reduction in angiographic restenosis with DES is accompanied by improved clinical durability, while confirming that any potential benefit is not offset by excess early procedural risk.

INTRODUCTION; Restenosis after stenting with a bare-metal stent (BMS) is the main cause of recurrence of stroke globally. Intracranial atherosclerotic stenosis (ICAS) is a cause of ischemic stroke worldwide with a particularly high disease burden in Asian populations. Symptomatic intracranial atherosclerotic stenosis (sICAS) defined by a transient ischemic attack (TIA) or ischemic stroke attributable to an intracranial atherosclerotic lesion carries a substantial risk of recurrent cerebrovascular events. This risk is particularly pronounced among patients with stenosis of 70%–99%. Treatment option includes Antiplatelet therapy and aggressive management of risk factors. Aggressive medical management remains the cornerstone of stroke prevention in patients with symptomatic severe ICAS. Randomized trials evaluating intracranial angioplasty and stenting however have highlighted periprocedural complications. In the SAMMPRIS trial intracranial stenting with the Wingspan system was associated with a higher 30-day risk of stroke or death compared with aggressive medical therapy alone. CASSISS trials demonstrated the results as above regarding adding conventional stenting to optimized medical therapy.Despite this intracranial revascularization may remain an option for selected patients with symptomatic disease particularly when recurrent ischemic events occur despite optimized medical therapy. An important limitation of bare-metal stents (BMS) is in-stent restenosis (ISR) resulting from neointimal hyperplasia and recurrent luminal narrowing within or adjacent to the stented segment. ISR may compromise the durability of revascularization. Contribute to subsequent ischemic events in the territory supplied by the treated vessel. Drug-eluting stents (DES) have been developed to address this limitation by delivering agents locally and thereby potentially suppressing neointimal proliferation. In a clinical trial of patients with symptomatic high-grade ICAS DES implantation was associated with a markedly lower 1-year ISR rate than BMS implantation (9.5% vs 30.2%) while the incidence of ischemic stroke recurrence in the target-vessel territory from day 31 through 1 year was also lower with DES. However the 30-day rate of stroke or death did not differ significantly between the two treatment strategies highlighting the need to evaluate both procedural safety and longer-term efficacy. Despite a lot of literature is available although metaanalysis is done these recent systematic reviews have found that DES are associated with ISR than BMS the literature has continued to expand and published syntheses have varied in their eligibility criteria and outcome definitions. The 2024 Gong et al. Meta-. The 2025 Mirjani et al. Meta-analysis support a restenosis benefit but an updated review is justified if it incorporates newly available comparative evidence and applies a more homogeneous clinical question. In particular restricting the population to adults with TIA or non-disabling ischemic stroke due to severe symptomatic angiographically confirmed 70%-99% ICAS reduces clinical heterogeneity and improves the direct relevance of the pooled estimates.Accordingly this updated meta-analysis will compare DES with BMS using three complementary outcomes: (1) 30-day any-stroke or all-cause mortality as the primary safety outcome; (2) radiographically confirmed ISR within 1 year as the primary efficacy outcome; and (3) target-vessel ischemic stroke recurrence within 12 months as the key clinical performance outcome. This focused approach will clarify whether a reduction in restenosis, with DES is accompanied by improved clinical durability while confirming that any potential benefit is not offset by excess early procedural risk.

INTRODUCTION; Restenosis after stenting with a bare-metal stent (BMS) is the main cause of recurrence of stroke globally. Intracranial atherosclerotic stenosis (ICAS) is a cause of ischemic stroke worldwide with a particularly high disease burden in Asian populations. Symptomatic intracranial atherosclerotic stenosis (sICAS) defined by a transient ischemic attack (TIA) or ischemic stroke attributable to an intracranial atherosclerotic lesion carries a substantial risk of recurrent cerebrovascular events. This risk is particularly pronounced among patients with stenosis of 70%–99%. Treatment option includes Antiplatelet therapy and aggressive management of risk factors. Aggressive medical management remains the cornerstone of stroke prevention in patients with symptomatic severe ICAS. Randomized trials evaluating intracranial angioplasty and stenting however have highlighted periprocedural complications. In the SAMMPRIS trial intracranial stenting with the Wingspan system was associated with a higher 30-day risk of stroke or death compared with aggressive medical therapy alone. CASSISS trials demonstrated the results as above regarding adding conventional stenting to optimized medical therapy.Despite this intracranial revascularization may remain an option for selected patients with symptomatic disease particularly when recurrent ischemic events occur despite optimized medical therapy. An important limitation of bare-metal stents (BMS) is in-stent restenosis (ISR) resulting from neointimal hyperplasia and recurrent luminal narrowing within or adjacent to the stented segment. ISR may compromise the durability of revascularization. Contribute to subsequent ischemic events in the territory supplied by the treated vessel. Drug-eluting stents (DES) have been developed to address this limitation by delivering agents locally and thereby potentially suppressing neointimal proliferation. In a clinical trial of patients with symptomatic high-grade ICAS DES implantation was associated with a markedly lower 1-year ISR rate than BMS implantation (9.5% vs 30.2%) while the incidence of ischemic stroke recurrence in the target-vessel territory from day 31 through 1 year was also lower with DES. However the 30-day rate of stroke or death did not differ significantly between the two treatment strategies highlighting the need to evaluate both procedural safety and longer-term efficacy. Despite a lot of literature is available although metaanalysis is done these recent systematic reviews have found that DES are associated with ISR than BMS the literature has continued to expand and published syntheses have varied in their eligibility criteria and outcome definitions. The 2024 Gong et al. Meta-. The 2025 Mirjani et al. Meta-analysis support a restenosis benefit but an updated review is justified if it incorporates newly available comparative evidence and applies a more homogeneous clinical question. In particular restricting the population to adults with TIA or non-disabling ischemic stroke due to severe symptomatic angiographically confirmed 70%-99% ICAS reduces clinical heterogeneity and improves the direct relevance of the pooled estimates.Accordingly this updated meta-analysis will compare DES with BMS using three complementary outcomes: (1) 30-day any-stroke or all-cause mortality as the primary safety outcome; (2) radiographically confirmed ISR within 1 year as the primary efficacy outcome; and (3) target-vessel ischemic stroke recurrence within 12 months as the key clinical performance outcome. This focused approach will clarify whether a reduction in restenosis, with DES is accompanied by improved clinical durability while confirming that any potential benefit is not offset by excess early procedural risk. humazine the text as possible as it can be

Reading File

Introduction

Intracranial atherosclerotic stenosis (ICAS) is an important cause of ischemic stroke worldwide and carries a particularly high burden in Asian populations. Symptomatic ICAS, defined as a transient ischemic attack (TIA) or ischemic stroke attributable to an intracranial atherosclerotic lesion, is associated with a considerable risk of recurrent cerebrovascular events. This risk is especially high in patients with severe stenosis, defined as 70%-99% luminal narrowing.

The mainstay of treatment for symptomatic severe ICAS is aggressive medical management, including antiplatelet therapy and intensive control of modifiable vascular risk factors. Randomized trials of intracranial angioplasty and stenting have raised concerns regarding procedural safety. In the SAMMPRIS trial, treatment with the Wingspan stent system was associated with a higher 30-day risk of stroke or death than aggressive medical therapy alone. Similarly, the CASSISS trial did not demonstrate an added benefit of conventional stenting over optimized medical treatment in the overall population of patients with severe symptomatic ICAS.

Nevertheless, intracranial revascularization may still be considered in carefully selected patients, particularly those who continue to experience recurrent ischemic events despite optimized medical therapy. A major limitation of conventional bare-metal stents (BMS) is in-stent restenosis (ISR), which results from neointimal hyperplasia and recurrent narrowing within, or immediately adjacent to, the stented segment. ISR can undermine the long-term durability of revascularization and may contribute to recurrent ischemia in the territory supplied by the treated vessel.

Drug-eluting stents (DES) were developed to address this limitation. By locally delivering antiproliferative agents, DES may inhibit neointimal proliferation and reduce restenosis after stent implantation. In a randomized clinical trial among patients with symptomatic high-grade ICAS, DES implantation was associated with a substantially lower 1-year ISR rate than BMS implantation (9.5% vs 30.2%). DES use was also associated with a lower incidence of target-vessel ischemic stroke recurrence from day 31 through 1 year. However, the 30-day rate of stroke or death did not differ significantly between the two strategies, emphasizing the need to assess both early procedural safety and longer-term vessel patency and clinical outcomes.

Although prior systematic reviews and meta-analyses, including those by Gong et al. in 2024 and Mirjani et al. in 2025, have suggested that DES reduce ISR compared with BMS, the evidence base has continued to expand. Existing reviews have differed in their eligibility criteria, included populations, outcome definitions, and follow-up periods. A focused updated meta-analysis is therefore warranted to incorporate newer comparative evidence and address a more clinically homogeneous population.

Accordingly, this meta-analysis will evaluate DES versus conventional BMS in adults presenting with TIA or non-disabling ischemic stroke due to severe, symptomatic, angiographically confirmed ICAS (70%-99% stenosis). The primary safety outcome will be any stroke or all-cause mortality within 30 days after the procedure. The primary efficacy outcome will be radiographically confirmed ISR within 1 year. Target-vessel ischemic stroke recurrence within 12 months will be assessed as the key secondary clinical outcome. By evaluating procedural safety, angiographic durability, and subsequent ischemic events together, this review aims to determine whether the lower restenosis risk associated with DES translates into meaningful clinical benefit without increasing early procedural harm.