Paclitaxel Drug-Coated Balloon Angioplasty for Medically Refractory Intracranial Atherosclerotic Disease: A US Single-Center Experience With the AGENT Balloon

Abstract

BACKGROUND:

Intracranial atherosclerotic disease is associated with up to 10% of ischemic strokes and a high risk of recurrence. Endovascular treatments including percutaneous transluminal angioplasty and stenting have failed to demonstrate improved outcomes compared with medical therapy alone. Drug-coated balloon (DCB) angioplasty has emerged as a promising alternative, though its safety and durability remain uncertain.

METHODS:

This single-center retrospective study analyzed consecutive patients with refractory intracranial atherosclerotic disease treated with AGENT drug-coated balloon submaximal angioplasty. Stenosis was quantified according to the WASID criteria (Warfarin-Aspirin Symptomatic Intracranial Disease). Patients were treated either for refractory large-vessel occlusion during thrombectomy (emergency rescue) or for recurrent ischemic symptoms from high-grade stenosis (elective primary). Primary outcome was technical success, defined as <50% residual stenosis after DCB angioplasty without the need for adjunctive percutaneous transluminal angioplasty and stenting. Safety outcomes included periprocedural intracranial hemorrhage, vessel dissection, symptomatic reocclusion, ischemic stroke, and mortality at 1 month and 3 months.

RESULTS:

Of the 11 identified patients, 9 underwent successful DCB angioplasty, 5 for emergent rescue therapy, and 4 for elective primary therapy. There was a combined technical success rate of 78%, with no major procedural complications. Mean stenosis reduction was 53.6% (paired Wilcoxon P=0.014; preprocedure mean [SD] stenosis 90.8% [±8.6%] to postprocedure 37.3% [±33.4%]). Restenosis occurred in 3 of the 4 (75%) elective primary patients on follow-up imaging at a mean of 64 days postprocedure, without recurrent ischemic events. Follow-up angiographic data for the emergent rescue cohort was unavailable, though no symptomatic ischemic events were reported.

CONCLUSIONS:

Paclitaxel-coated AGENT DCB submaximal angioplasty was safe and yielded immediate improvements in luminal diameter. However, high rates of restenosis emphasize the need for innovative devices and larger prospective studies to define its therapeutic role for refractory intracranial atherosclerotic disease.

CLINICAL PERSPECTIVE.

What Is New?

• This study provides a single-center experience of the paclitaxel-coated AGENT drug-coated balloon for submaximal angioplasty in patients with refractory intracranial atherosclerotic disease.

• AGENT drug-coated balloon achieved significant immediate luminal gain without major peri-procedural complications, vessel dissection, or symptomatic stroke within 30 days.

What Are the Clinical Implications?

• Although paclitaxel-coated drug-coated balloon angioplasty is a feasible temporizing option in carefully selected patients with refractory intracranial atherosclerotic disease, it should not replace best medical management as the first-line due to high rates of short-term restenosis.

• These findings support further multicenter prospective studies to define the durability, optimal procedural technique, and clinical role of drug-coated balloon angioplasty in neurointerventional practice.

Intracranial atherosclerotic disease (ICAD) is associated with up to 10% of ischemic strokes and is associated with a high risk of recurrence. The landmark SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) and VISSIT (Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) randomized clinical trials demonstrated that percutaneous transluminal angioplasty and stenting (PTAS) did not improve outcomes compared with maximum medical therapy alone.^1–3 Early data with paclitaxel drug-coated balloons (DCBs), such as SeQuent please and Taijieweiye, show technical feasibility, though optimal dosing, procedural technique, and long-term outcomes remain unclear.⁴ Moreover, neither device is commercially available in the United States, thus limiting the evidence-based application of this strategy in clinical practice for the US population.

Here, we present the first US single-center therapeutic experience with the paclitaxel-coated AGENT DCB (Boston Scientific, Marlborough, MA) for submaximal angioplasty of symptomatic ICAD refractory to maximal medical therapy, highlighting technical performance, safety profile, and clinical outcomes. The analysis is stratified by indication, emergent rescue angioplasty during failed mechanical thrombectomy versus elective primary angioplasty for recurrently symptomatic patients despite maximal medical therapy, to inform the design of future prospective investigations.

Methods

Data Availability

The data that support the findings of this study are available from the corresponding author on reasonable request.

Ethical Approval

Institutional review board approval was obtained for this study, with a waiver of informed consent for the retrospective review of deidentified clinical data. Patient consent was waived as the article contains a compiled retrospective analysis with no individual personally identifiable information.

Study Population

Institutional review board approval was obtained for this study, with a waiver of informed consent for the retrospective review of deidentified clinical data. We reviewed all consecutive intracranial DCB angioplasties performed at our tertiary care center between January 2025 and July 2025. Eligible patients were adults (≥18 years) with symptomatic ICAD who underwent submaximal angioplasty for either (1) refractory large-vessel occlusion during mechanical thrombectomy, defined as failure to achieve recanalization (modified Thrombolysis in Cerebral Infarction <2b) after ≥3 device passes or immediate reocclusion (emergent rescue cohort); or (2) high-grade (>70%) stenosis with recurrent ischemic symptoms despite maximal medical therapy (elective primary cohort). Patients for whom DCB angioplasty was selected but the balloon could not be advanced technically to the target lesion were excluded from the final analysis (Figure 1).

Figure 1.

Patient selection flow diagram. Flow of patients through the study, including exclusions and assignment to emergent rescue (n=5) and elective primary (n=4) cohorts. DCB indicates drug-coated balloon.

Procedure

All procedures were performed under general anesthesia by experienced neurointerventionalists using biplane digital subtraction angiography. All patients were pretreated with dual antiplatelet therapy and systemic anticoagulation with intravenous heparin was administered to maintain an activated clotting time of 250 to 300 seconds throughout the procedure.

Conventional techniques used for DCB angioplasty, particularly with devices, such as the SeQuent Please, often involve vessel predilation with an uncoated balloon to achieve a residual stenosis of <50% before the application of the DCB.^5–7 In the present study, we deemed this unnecessary as robust evidence from multicenter randomized trials for coronary DCB angioplasty suggests that the AGENT DCB is able to successfully dilate the affected stenotic vessel primarily.⁸ As such, an AGENT DCB selected to match ≈80% of anticipated parent vessel diameter was advanced primarily over the microwire to span the entire stenotic lesion. Inflation was performed to nominal pressure for 60 seconds to allow uniform drug transfer to the vessel wall (Figure 2). If significant residual stenosis (>50%) persisted, a second prolonged inflation was attempted at the neurointerventionalist’s discretion.

Figure 2.

Illustrative schematic of the procedural workflow for drug-coated balloon angioplasty. A representative intracranial stenotic lesion (left) is shown before intervention. After submaximal inflation of the AGENT paclitaxel-coated balloon (middle), paclitaxel (dark cyan dots) is locally delivered to the arterial wall. The postprocedure result (right) demonstrates improved luminal caliber with drug deposition along the endoluminal surface.

After submaximal angioplasty, repeat angiography was performed to evaluate the residual stenosis, flow, and potential complications, including dissection or vessel rupture. Intracranial stenting was reserved for cases of inadequate angiographic result, flow-limiting dissection, or elastic recoil after balloon angioplasty. Postprocedural antiplatelet therapy consisted of dual antiplatelet therapy with aspirin and a P2Y12 inhibitor, continued for a duration specified per institutional protocol.

Data Collection and Outcomes

Clinical and procedural data were abstracted from electronic medical records and angiographic archives. All consecutive patients meeting inclusion criteria were analyzed to minimize selection bias. Lesion characteristics, procedural details (balloon size, inflation time), and use of adjunctive devices were recorded. Stenosis severity was quantified via digital subtraction angiography by the treating neurointerventionalist according to the WASID criteria (Warfarin-Aspirin Symptomatic Intracranial Disease), both before and after AGENT DCB submaximal angioplasty, with all procedural data collected from electronic medical records and angiographic archives to reduce measurement bias. The primary outcome was technical success, defined as <50% residual stenosis after DCB angioplasty without the need for adjunctive PTAS. Safety outcomes included periprocedural intracranial hemorrhage, vessel dissection, symptomatic reocclusion, ischemic stroke, and mortality at 1 month and 3 months.

Statistical Analysis

Given the small cohort size, analyses were primarily descriptive. Continuous variables are presented as mean±SD, whereas categorical variables are reported as counts and percentages. The distribution of continuous variables was assessed; no formal test for normality was performed given the small sample size. The within-patient change in stenosis severity was assessed using the paired Wilcoxon signed-rank test. No formal sensitivity analyses were conducted due to the small sample size; all analyses are descriptive. All statistical tests were 2-sided with an alpha of 0.05. P values are considered exploratory and were not adjusted for multiplicity. No missing data were present for primary or secondary outcomes. All demographic, clinical, and procedural variables were complete for the included patients.

Results

Patient Characteristics

A total of 11 consecutive patients (5 female, 45%) with medically refractory ICAD were identified as suitable candidates for AGENT DCB submaximal angioplasty. Two patients initially selected for DCB angioplasty were excluded intraprocedurally because of technical inability to advance the AGENT DCB to the target lesion due to proximal vessel tortuosity. Eight out of the remaining 9 patients had hypertension (88.9%), with other prevalent risk factors including hyperlipidemia (88.9%) and diabetes (33.3%). The preprocedure National Institutes of Health Stroke Scale score was variable with mean (±SD) of 6.6 (±8.2). Further demographic data is presented in Table 1.

Table 1.

Baseline Demographics and Clinical Characteristics

Seven of the 11 selected patients presented with acute ischemic stroke and underwent mechanical thrombectomy with failure to achieve recanalization (modified Thrombolysis in Cerebral Infarction <2b) after ≥3 device passes or immediate reocclusion (emergent rescue cohort). Two patients from this emergency rescue cohort were excluded from the analysis because of technical inability to advance the AGENT DCB to the target lesion due to proximal vessel tortuosity. The remaining 5 patients underwent DCB angioplasty, 3 to the middle cerebral artery, 1 to the posterior cerebral artery, and 1 to the midbasilar artery.

Four of the 11 patients were selected for high-grade (>70%) stenotic lesions with recurrent ischemic symptoms despite maximal medical therapy (elective primary cohort). All 4 patients underwent DCB angioplasty, 2 to the distal intracranial internal cerebral artery, 1 to the middle cerebral artery, and 1 to the midbasilar artery. Patient-level characteristics and procedural outcomes are described in Table 2.

Table 2.

Patient-Level Characteristics and Procedural Outcomes After DCB Angioplasty

The mean preprocedural stenosis, as measured by the WASID criteria, was not significantly different between the 2 cohorts (mean [SD] of stenosis 92.0 [±8.4%] in emergent rescue cohort and 89.2% [±10.5%] in the elective primary cohort).

Safety Outcomes

AGENT DCB submaximal angioplasty was very well tolerated in this patient population. Three patients in the emergency rescue cohort had small asymptomatic petechial hemorrhages noted on the follow-up magnetic resonance imaging, all classified as hemorrhagic infarction type 1 on the Heidelberg Bleeding Classification, thought to be related to natural stroke progression rather than the DCB angioplasty procedure.⁹ No major symptomatic bleeding events were observed. There were no reports of peri-procedural vessel dissections, symptomatic reocclusions, and ischemic strokes in either cohort within 30 days of the intervention.

Efficacy Outcomes

Nine of the 11 selected patients underwent successful AGENT DCB submaximal angioplasty, with significant improvements in luminal diameter, with a mean absolute reduction of 53.6% (paired Wilcoxon P=0.014; preprocedure mean [SD] stenosis 90.8% [±8.6%] to postprocedure 37.2% [±33.4%]). Efficacy of the intervention was not significantly different between the 2 cohorts (see Figure 3). Seven of the total 9 patients (78%) met the primary outcome for technical success with <50% residual stenosis, with only 2 patients, both in the emergency rescue cohort, requiring rescue PTAS for persistent flow-limiting stenosis despite DCB angioplasty to the middle cerebral artery.

Figure 3.

Preballoon vs postballoon angioplasty stenosis severity. Bar plot comparing mean percentage stenosis (prebasilar artery [BA]) and after (post-BA) submaximal angioplasty with the AGENT drug-coated balloon. Results are shown for the entire patient cohort (all), the emergency rescue cohort (angioplasty for refractory large-vessel occlusion during thrombectomy), and the elective primary cohort (angioplasty for recurrent symptoms from high-grade intracranial atherosclerotic disease despite medical therapy). Error bars represent SD.

Follow-Up Outcomes

There was limited 3-month angiographic follow-up data to assess for delayed asymptomatic restenosis, with none of the patients in the emergent rescue therapy cohort obtaining repeat imaging as of yet. All 4 patients in the elective primary cohort did receive follow-up noninvasive angiographic imaging (mean follow-up 64 days), with 3 of the 4 (75%) patients showing recurrence of the intracranial stenosis but without clinical symptomatic ischemic events.

There were no incidences of procedure-related mortality in either of the cohorts within the 3-month follow-up period. However, 3 patients, again all in the emergency rescue cohort, did die from nonprocedure-related causes, including 1 from gastrointestinal bleed and pneumonia leading to refractory septic shock, 1 from goals of care discussions due to completed bilateral cerebellar and brainstem ischemic stroke, and 1 from self-inflicted asphyxiation as part of a suicide attempt.

Discussion

This single-center US experience demonstrates that submaximal angioplasty with the commercially available paclitaxel-coated AGENT DCB is technically feasible, safe, and effective in reducing intraluminal stenosis in patients with symptomatic ICAD refractory to maximum medical therapy. Our results show a combined 78% technical success rate, with no major periprocedural complications and low need for adjunctive stenting. These findings add to the limited body of literature on DCB angioplasty for ICAD, particularly in the United States where the SeQuent Please DCB and Taijieweiye DCB used in the existing literature are not commercially available.

ICAD accounts for up to 10% of ischemic strokes and is associated with a high risk of recurrence.¹⁰ The landmark SAMMPRIS and VISSIT randomized clinical trials demonstrated that PTAS did not improve outcomes compared with maximum medical therapy alone.^1–3 These findings limited the use of PTAS but left a therapeutic gap for patients with ICAD refractory to medical therapy. Alternative strategies including primary balloon angioplasty alone have been attempted, but with limited success and high periprocedural complications.¹¹

DCB angioplasty has emerged as a promising approach, delivering localized antiproliferative therapy while minimizing the risks of in-stent restenosis and delayed thrombosis associated with permanent scaffolds.^12,13 Early reports using paclitaxel-coated DCBs, particularly the SeQuent Please resveratrol‑coated paclitaxel balloon (SeQuent Please; B. Braun, Berlin, Germany), have demonstrated technical feasibility and short-term angiographic improvement.^6,14 This is further being investigated in the ongoing multicenter randomized Dr BEYOND trial (Drug-Coated Balloon for Endovascular Treatment of Symptomatic Intracranial Stenotic Disease), which compares the efficacy and safety of DCB angioplasty with the paclitaxel-coated Taijieweiye DCB to bare-metal stenting with the Wingspan stent system.¹⁵ However, neither the SeQuent Please DCB nor the Taijieweiye DCB are available for commercial use in the United States, thus limiting safety and efficacy investigations and evidence-based application of this strategy in US clinical practice.

In addition, current literature remains sparse, with optimal drug dose, coating excipient, procedural workflow, and long-term outcomes remaining poorly defined. Notably, the recent BASIS trial (Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis; PMID: 39235816) comparing DCB angioplasty to medical therapy for symptomatic ICAD was terminated early due to the failure of the DCB arm to meet the noninferiority end point, which highlights the need for careful patient selection and procedural refinement. Furthermore, the AcoArt ICAD study (PMID: 40010849) demonstrated that the use of a novel paclitaxel-coated balloon achieved a 6-month angiographic restenosis rate of 12.5% in de novo ICAD lesions, suggesting that device design or specific patient factors may substantially impact outcomes.

AGENT (Boston Scientific, Marlborough, MA) is a US Food and Drug Administration–approved coronary DCB commercially available in the United States, with multicenter randomized trials demonstrating noninferiority compared with the SeQuent Please for in-stent coronary stenosis at 6 months and superiority against uncoated balloons in the AGENT IDE trial (A Clinical Trial to Assess the AGENT Paclitaxel Coated PTCA Balloon Catheter for the Treatment of Subjects With In-Stent Restenosis Investigational Device Exemption).^8,16 Unlike SeQuent Please, it employs a low‑dose (2 µg mm^-2) crystalline paclitaxel coating with an acetyl‑tributyl‑citrate excipient, and a laser‑bonded tip and bi‑segment shaft designed to enhance navigability in tortuous anatomy. Although widely used in the coronary circulation, the AGENT DCB has unique delivery and pharmacokinetic characteristics which have not been systematically studied for intracranial use.

Our series provides early insight into the use of the paclitaxel-coated AGENT DCB for submaximal angioplasty of symptomatic ICAD refractory to maximal medical therapy. We describe 11 patient cases, 7 as emergent rescue therapy for refractory large-vessel occlusion during mechanical thrombectomy and 4 as elective primary therapy for high-grade (>70%) stenosis with recurrent ischemic symptoms despite maximal medical therapy. Only 2 of the 11 DCB angioplasty attempts were unsuccessful, both due to the highly tortuous anatomy of their proximal vessels. Newer device interactions specifically designed for intracranial use may improve the maneuverability and deliverability of DCBs to avoid such events in the future.

Nine patients underwent successful intracranial AGENT DCB submaximal angioplasty, 5 as emergency rescue therapy and 4 as elective primary therapy. Safety outcomes were favorable with no peri-procedural major hemorrhages, vessel dissections, symptomatic reocclusions, ischemic strokes in either cohort within the first month. Petechial hemorrhages observed in 3 patients within the emergent rescue cohort were asymptomatic, classified HH-1 (Hunt Hess scale 1) on the Heidelberg Bleeding Classification, and consistent with hemorrhagic transformation of ischemic stroke rather than a procedural complication. Nonetheless, multiple manipulations of the vascular endothelium can induce injury and, combined with dual antiplatelets and systemic heparinization, can increase the risk of vessel dissection or rupture.^17,18 Mortality events were unrelated to the procedure.

Technical efficacy of the procedure was acceptable in the short-term. There were significant reductions in intraluminal narrowing to <50% residual stenosis in 7 of the 9 patients (78%). Two patients, both undergoing emergency rescue therapy, remained refractory and required rescue PTAS, comparable to the failure rates described in current literature.¹⁹ Both had middle cerebral artery stenosis, and failure of DCB angioplasty was likely mediated by the patient’s individual pathology rather than the location of the stenosed vessel. Of the successful angioplasties, there were no reports of symptomatic reocclusions or ischemic strokes within 3 months.

However, the durability of DCB angioplasty remains a concern. Three of the 4 elective patients in our cohort demonstrated restenosis at short-term follow-up despite dual antiplatelet therapy. This finding echoes prior experience with angioplasty and underscores the need to temper initial enthusiasm: while DCB angioplasty may serve as a safe temporizing strategy, it is unlikely to represent a definitive solution for refractory ICAD where stenotic lesions are prone to recoil and restenosis.²⁰ Chen et al⁴ have identified predictors of restenosis after DCB treatment. Meanwhile, Xue et al²¹ reported 100% technical success with no restenosis when treating intracranial in-stent restenosis. In contrast, the universal restenosis in our primary cohort suggests that de novo atherosclerotic plaques may have a more aggressive biology.²² DCBs designed specifically for the unique mechanical and biological environment of intracranial arteries may be able to achieve durable results. Coating with medications other than paclitaxel, such as sirolimus, may also further improve long-term efficacy.²³ Future research should investigate the optimal medication, dosing, duration of endothelial contact, distinct vascular geometries, vessel wall characteristics and other technical details that could make the procedure more durable.

A comparative overview of contemporary ICAD endovascular studies is presented in Table 3.^24–26 When contextualized against existing evidence, the most prominent divergence is the markedly higher restenosis rate observed in the elective AGENT cohort (75%) compared with the pooled 7.34% rate reported in the systematic review.²⁴ Several factors may account for this discrepancy, including the absence of predilation in the present series, potential differences in drug-delivery and mechanical properties unique to the AGENT platform, and the refractory de novo lesion phenotype treated in this cohort, which may predispose to rapid neointimal recurrence.

Table 3.

Comparative Overview of Contemporary ICAD Angioplasty and DCB Evidence

The BASIS randomized trial established that uncoated balloon angioplasty is superior to aggressive medical therapy alone, providing a contemporary benchmark for endovascular management of symptomatic ICAD.²⁵ The current findings demonstrate that while AGENT DCB submaximal angioplasty is technically feasible and acutely safe, its durability in this setting remains uncertain.

The broader efficacy of intracranial DCB therapy has yet to be defined. Ongoing randomized evaluation, most notably the Dr BEYOND trial comparing a paclitaxel DCB with the Wingspan stent, will be essential to delineate the role of DCBs within the therapeutic hierarchy for ICAD.²⁶

Limitations

Our findings provide a proof-of-concept for the use of AGENT DCB submaximal angioplasty for symptomatic refractory ICAD to inform clinical practice and future device development. Nevertheless, our findings have several limitations. It is a single-center, retrospective analysis with a small sample size and heterogeneous patient population, which may limit generalizability. Selection bias is possible, as only patients in whom the AGENT DCB could be advanced were included. The study lacks a comparator group, precluding direct evaluation of efficacy relative to medical therapy or alternative endovascular strategies. Procedurally, unlike most international studies with SeQuent Please, we did not perform predilation with a conventional balloon; while cardiac literature suggests that the semicompliant AGENT DCB may provide sufficient submaximal angioplasty without predilation, this assumption requires further evaluation in ICAD. Follow-up was short and incomplete, particularly with limited 3-month imaging in the emergent rescue cohort, preventing systematic assessment of asymptomatic restenosis.

To our knowledge, this is the first evidence-based case series systematically investigating the use of paclitaxel-coated AGENT DCB submaximal angioplasty as an off-label alternative for patients with symptomatic refractory ICAD, particularly in the United States where commercial availability of DCBs like SeQuent Please and Taijieweiye remains uncertain. The study shows significant immediate improvements in intraluminal stenosis with low peri-procedural complication rates. However, the high rate of restenosis in the elective primary cohort underscores that this approach is best considered a temporizing measure rather than a definitive solution. Future prospective, multicenter studies, such as Dr BEYOND, are essential to define the long-term efficacy of DCB angioplasty and to guide the design of next-generation devices tailored specifically for the intracranial circulation with an emphasis on patient-specific factors like lesion morphology and inflammatory state. Until such evidence is available, DCB angioplasty should be considered a salvage strategy rather than a first-line intervention.

Conclusions

Paclitaxel-coated AGENT DCB submaximal angioplasty was safe and produced significant immediate improvements in luminal diameter for patients with symptomatic ICAD refractory to maximum medical therapy. However, the effect was short-lived, and a significant number of patients experienced restenosis, though without any reports of recurrent ischemic events. Taken together, these findings suggest that DCB angioplasty is a feasible temporizing option in carefully selected patients but should not replace best medical management as first-line therapy. Larger, prospective studies are required to clarify the safety, durability, and ultimate role of this emerging strategy.

ARTICLE INFORMATION

Acknowledgments

The authors thank Mercy Health–St. Vincent Medical Center (Toledo, OH) for institutional support during the conduct of this study.

Author Contributions

Dr Chaudhari, Z.M. Rosenstein, and R. Kamal were the primary authors responsible for the writing of the manuscript. Drs Chaudhari, Zaidat, Lin, Ramirez-Abreu, Almajali, Al-Ghetaa, Ashouri, and Khan were directly involved in the clinical care of the patients and revision of the manuscript. R. Kamal and Z.M. Rosenstein created the tables and figures. Dr Lin provided senior review and revisions of the manuscript. Dr Zaidat provided overall project supervision. All authors have read and approved the final manuscript for submission.

Sources of Funding

None.

Disclosures

Dr Zaidat serves on the editorial board of Stroke: Vascular and Interventional Neurology. Editorial board members are not involved in the handling or final disposition of submissions.

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