Impact of Aneurysm Size and Flow Diverter Use on Outcomes After Endovascular Therapy of Unruptured Paraclinoid Aneurysms

Abstract

BACKGROUND:

Flow diverters (FDs) are increasingly used for unruptured paraclinoid aneurysms, especially large or giant ones. However, their benefit over conventional endovascular therapy remains unclear. This study evaluated outcomes after endovascular therapy of unruptured paraclinoid aneurysms, with aneurysm size as the primary exposure, and further examined the modifying effect of FD use.

METHODS:

We analyzed data of patients with unruptured paraclinoid aneurysms from the Japanese Registry of Neuroendovascular Therapy 4, a nationwide, multicenter registry enrolling patients who underwent endovascular therapy in 166 Japanese institutions from 2015 to 2019. The primary outcome was worsening in the modified Rankin Scale score ≥1 at 30 days. Secondary outcomes included ischemic and hemorrhagic complications. Outcomes were compared by aneurysm size (<10 mm versus ≥10 mm) and further stratified by FD use.

RESULTS:

Of 3860 patients (3326 women, median age 59 years), 3048 had aneurysms <10 mm and 776 had aneurysms ≥10 mm. FD use was more common in aneurysms ≥10 mm (64.2% versus 3.0%). Worsening in modified Rankin Scale score occurred in 5.3% with aneurysms ≥10 mm versus 2.0% with <10 mm (adjusted odds ratio, 2.28 [95% CI, 1.48–3.49]). Ischemic complications were more frequent with larger aneurysms (5.7% versus 4.0%, P=0.035), though not significant after multivariable adjustment (adjusted odds ratio, 1.26 [95% CI, 0.87–1.84]). Hemorrhagic complication rates were similarly low across groups. There was no significant difference in modified Rankin Scale score worsening by FD use, regardless of aneurysm size. FD use was associated with significantly fewer ischemic complications in aneurysms ≥10 mm (3.2% versus 10.1%, P<0.001), but not in aneurysms <10 mm (4.3% versus 3.9%, P=0.88; P for interaction=0.03).

CONCLUSIONS:

Endovascular embolization of unruptured paraclinoid aneurysms ≥10 mm was associated with a higher morbidity compared with aneurysms <10 mm. FD use may reduce ischemic complications in larger aneurysms; however, this benefit was not clearly reflected in 30-day functional outcomes.

GRAPHIC ABSTRACT:

CLINICAL PERSPECTIVE.

What Is New?

• Using a large nationwide registry from Japan, this study suggests that unruptured paraclinoid aneurysms ≥10 mm, compared with those <10 mm, are associated with a higher risk of 30-day functional worsening after endovascular therapy.

• Larger unruptured paraclinoid aneurysms were also associated with a higher frequency of ischemic complications.

• In larger aneurysms, flow diverter use was associated with fewer ischemic complications, but this did not translate into a reduction in the short-term functional morbidity.

What Are the Clinical Implications?

• After endovascular therapy, patients with unruptured paraclinoid aneurysms ≥10 mm may have a higher short-term risk of functional worsening than those with smaller aneurysms, regardless of treatment strategy.

• Further studies with longer-term follow-up are needed to clarify whether differences in procedural complication profiles translate into meaningful functional benefit over time.

Aneurysms arising from the internal carotid artery between the site of its exit from the roof of the cavernous sinus and the origin of the posterior communicating artery are collectively referred to as paraclinoid aneurysms.^1–3 Paraclinoid aneurysms are associated with a potential risk of subarachnoid hemorrhage. The UCAS Japan (Unruptured Cerebral Aneurysm Study of Japan) investigators reported that the annual rupture rate of internal carotid artery aneurysms, including paraclinoid aneurysms, was 1.07% for those with a maximum diameter of 7 to 24 mm and 10.61% for those with a maximum diameter of ≥25 mm.⁴ Large and giant paraclinoid aneurysms often cause cranial neuropathy that affect cranial nerves II, III, IV, V, and VI.^5,6 Large or giant paraclinoid aneurysms can be candidates for treatment, but these aneurysms present unique challenges for microsurgical clipping, owing to their anatomic location adjacent to the anterior clinoid process, optic nerve, and cavernous sinus.² Consequently, endovascular therapy has become the preferred treatment modality for paraclinoid aneurysms, largely due to its less invasive nature and favorable safety profile.⁷

The flow diverter (FD) is a device that controls blood flow into the aneurysms without introducing a catheter into the aneurysms and filling it with embolization materials, such as coils, thereby preventing aneurysm rupture while preserving the parent artery.⁸ In particular, treatment with FDs is expected to improve cranial neuropathy symptoms because it can achieve aneurysmal regression without placing a metallic implant within the aneurysmal sac.⁶ However, treatment with an FD requires antithrombotic therapy before and after treatment, and proficiency in handling the device is also necessary.^9,10 Furthermore, the short- to long-term outcomes, including ischemic and hemorrhagic complications associated with FD use, have not been established, and its superiority over conventional endosaccular embolization techniques has not been well determined.^11,12

FDs have been available in Japan since 2015 and were approved for use in paraclinoid aneurysms from their initial introduction. JR-NET4 (Japanese Registry of Neuroendovascular Therapy 4) was a nationwide, multicenter registry that enrolled patients who underwent neuroendovascular therapy between 2015 and 2019.^13–17 As the registry period coincided with the growing adoption of FDs in clinical practice, the JR-NET4 data set provides a valuable opportunity to compare the safety and effectiveness of FDs with conventional endovascular techniques. In this study, we evaluated the outcomes of endovascular embolization for unruptured paraclinoid aneurysms, with aneurysm size as the primary exposure, and further examined the modifying effect of FD use.

Methods

Anonymized data supporting the findings of this study are available from the corresponding author (T.S.), on reasonable request and after permission from the JR-NET4 steering committee.

Study Design and Patients

JR-NET4 was a nationwide, multicenter, retrospective observational study conducted in Japan. The purpose of JR-NET4 was to establish guiding principles for standard treatment and physician education by understanding the status of neuroendovascular treatment in Japan. Eligibility criteria for JR-NET4 were as follows: (1) patients for whom endovascular therapy was performed between January 2015 and December 2019; (2) patients for whom at least 1 Japanese Society for Neuroendovascular Therapy specialist was involved in the treatment; and (3) patients for whom at least 30 days had passed since the endovascular therapy at the time of registration. The primary end point of JR-NET4 was the modified Rankin Scale (mRS) score at 30 days after endovascular therapy. Overall, 63 230 cases were enrolled in JR-NET4 from 166 institutes across Japan. For the present analysis, consecutive patients from the JR-NET4 data set were eligible if they had unruptured paraclinoid aneurysms treated with endovascular embolization.

JR-NET4 and the present study were investigator-initiated. The funder had no role in the study design, analysis, management, or writing. The institutional review boards at Kobe City Medical Center General Hospital (approval no. zn200107) and all participating institutes approved this study. The requirement for written informed consent was waived because of the retrospective nature of this study and because the research was considered to pose no more than minimal risk to the subjects. Institutional review boards approved the exemption in accordance with the ethical guidelines for Medical and Health Research Involving Human Subjects in Japan. This study follows the STROBE reporting guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies (Supplemental Material).

Data Collection

The following clinical characteristics were collected: age, sex, mRS score at the time of endovascular therapy, the presence or absence of symptoms due to the unruptured aneurysm, aneurysm size (<3 mm, 3–<5 mm, 5–<7 mm, 7–<10 mm, 10–<25 mm, or ≥25 mm), wide-necked (neck width ≥4 mm or maximum dome-neck width ratio <1.5) or not for patients with aneurysm size <10 mm, retreatment or first-time treatment, and preprocedural antiplatelet therapy. Preprocedural antiplatelet agents included aspirin, ticlopidine, clopidogrel, prasugrel, and cilostazol. Preprocedural antiplatelet therapy was classified according to the number of antiplatelet agents used: no antiplatelet therapy, single antiplatelet therapy, dual antiplatelet therapy, and triple antiplatelet therapy or more.

For procedural characteristics, the following information were collected: the presence or absence of general anesthesia, systemic heparinization, FD use, technical success, angiographic complications, and anatomic outcomes. The FDs available in Japan during the period covered by JR-NET4 were Pipeline Flex (Medtronic), Pipeline Flex with Shield Technology (Medtronic), and FRED (Terumo/Microvention). FRED was approved for clinical use in Japan in August 2019 and was the only device approved for use in aneurysms <10 mm during the JR-NET4 study period. Angiographic complications were defined as events occurring in the angiographic room. Anatomic outcomes after aneurysm embolization were determined on the basis of 3-point Raymond-Roy Occlusion Classification scale: complete obliteration (class I), residual neck (class II), and residual aneurysm (class III).¹⁸

Clinical Outcomes

The primary outcome of the present analysis was a worsening of the mRS score by >1 at 30 days after the endovascular therapy. Secondary outcomes were ischemic complications, hemorrhagic complications, and death within 30 days after the endovascular therapy. Ischemic and hemorrhagic complications were defined as those occurring in the nervous system during or within 24 hours after endovascular therapy. Ischemic and hemorrhagic complications were both recorded if they were encountered in the same patient.

Statistical Analysis

The primary exposure of interest was aneurysm size, dichotomized at 10 mm (<10 mm versus ≥10 mm). FD use was treated as an effect modifier in subsequent analyses.

Patient characteristics were summarized as median (interquartile range) for continuous variables and as frequencies and percentages for categorical variables. Between-group comparisons were performed using the Mann-Whitney U test for continuous variables and the Pearson χ² test for categorical variables.

The outcomes were compared between patients with aneurysm size <10 mm and those with aneurysm size ≥10 mm using univariable and multivariable logistic regression models. The prespecified covariates for the multivariable adjustment were age, sex, mRS score of 0 to 2 or 3 to 5 at the time of endovascular therapy, the presence or absence of aneurysm symptom, retreatment or first-time treatment, and preprocedural antiplatelet therapy (no antiplatelet agent, single antiplatelet therapy, dual antiplatelet therapy, or triple antiplatelet therapy, or more). For each model, the odds ratios with 95% CIs were computed.

The interaction between aneurysm size and FD use on the outcomes was assessed by adding a multiplicative term of aneurysm size (<10 mm or ≥10 mm)-by-FD use (with FD or without FD) into the multivariable model for the association between outcomes and aneurysm size. Predictive marginal probabilities for the outcomes in patients with FD and in patients without FD were computed according to aneurysm sizes using the multivariable logistic model.

All reported P values were 2-tailed, and P<0.05 was considered statistically significant. Pairwise deletion was used for missing data handling. All statistical analyses were performed using the Stata/MP statistical package (version 17.0; Stata Corp, College Station, TX).

Results

Patients

Among the 13 889 patients of unruptured intracranial aneurysms registered in JR-NET4, 197 without data of preprocedural status, 121 without data of procedural information, and 47 without data of postprocedural information were deemed ineligible. Thus, 13 524 patients were included in the data set for analysis for unruptured intracranial aneurysms with endovascular therapy. In the present study, 3860 patients with unruptured paraclinoid aneurysms (3326 women; median age, 59 [interquartile range, 49–68] years; mRS score 0–2 at the time of endovascular therapy, 97.3%) were analyzed (Figure 1). The baseline characteristics are shown in Table 1. Endovascular techniques used were as follows: simple technique by which a single catheter and coils were used, 411 (10.7%); adjunctive techniques, 2849 (73.8%); FD use, 592 (15.3%); and other techniques, 8 (0.2%). Details of adjunctive techniques were as follows: double catheter technique, 4.5% (127/2849); balloon assist technique, 49.8% (1420/2849); stent-assisted coiling, 40.1% (1141/2849); and combination of these techniques, 5.6% (161/2849).

Figure 1.

Study flow chart. ICA indicates internal carotid artery; and mRS, modified Rankin Scale.

Table 1.

Baseline Characteristics According to Aneurysm Size

Of the patients analyzed, 3048 had aneurysm size <10 mm and 776 had aneurysm size ≥10 mm. Compared with patients with aneurysm size <10 mm, those with aneurysms ≥10 mm were older (63 [53–70.5] versus 58 [48–67] years; P<0.001), more frequently female (89.4% versus 85.3%; P=0.003), less independent with mRS score 0 to 2 (93.9% versus 98.2%; P<0.001), more frequently symptomatic (23.3% versus 9.8%; P<0.001), and had more cases of retreatment (14.9% versus 3.8%; P<0.001). Patients receiving antiplatelet therapy with multiple agents were more frequent in patients with aneurysms ≥10 mm than in those with aneurysms <10 mm.

The procedural characteristics are summarized in Table 2: general anesthesia was more frequent in patients with aneurysms ≥10 mm (84.8%) than in those with <10 mm (77.8%, P<0.001); FD use was more frequent (64.2% versus 3.0%, P<0.001) and anatomic outcome was more often a residual aneurysm in patients with aneurysm size ≥10 mm. Within patients with FD stenting, the use of platinum coils was more frequent in patients with aneurysms ≥10 mm (96.9%, 412/425) than in those with aneurysms <10 mm (79.3%, 65/83, P<0.001). Angiographic complications were not clearly different between aneurysm size <10 mm (2.7%) and ≥10 mm (2.2%, P=0.41), but aneurysm rupture was numerically more frequent with aneurysms <10 mm (0.9%) than ≥10 mm (0.3%, P=0.005), whereas distal thrombus embolization was numerically less frequent with aneurysms <10 mm (0.5%) than ≥10 mm (1.0%, P=0.10).

Table 2.

Procedural Characteristics

Clinical Outcomes

Overall, the primary outcome (worsening in mRS score by ≥1 point at 30 days posttreatment) occurred in 2.7% of patients. The proportion of aneurysms that were symptomatic at baseline was 26.9% among patients with mRS score worsening, compared with 12.1% among those without (P<0.001). Ischemic complications were observed in 4.3%, hemorrhagic complications in 1.6%, and deaths within 30 days in 0.1%. Approximately half of patients with mRS score worsening experienced ischemic complications, hemorrhagic complications, or both, and 3-quarters of deaths were accompanied by hemorrhagic complications (Figure S1).

The primary outcome was seen in 5.3% for patients with aneurysms ≥10 mm and 2.0% for those with <10 mm (P<0.001). The adjusted odds ratio of the primary outcome was 2.28 (95% CI, 1.48–3.49) for patients with aneurysms ≥10 mm compared with those with <10 mm referenced (Table 3). Ischemic complications were also more frequent in patients with aneurysms ≥10 mm (5.7% versus 4.0%; P=0.035), but after multivariable adjustment, there was no significant increase in the odds of ischemic complications for patients with aneurysms ≥10 mm (adjusted odds ratio, 1.26 [95% CI, 0.87–1.84]). Hemorrhagic complication rates were similar between the 2 groups (1.6% versus 1.5%; P=0.88). The rate of death within 30 days was similar between the 2 groups (0.1% versus 0.1%; P=0.81).

Table 3.

Clinical Outcomes

Analysis by FD Use

Across both aneurysm size groups, patients treated with and without FD showed no significant differences in age, sex, functional independence (mRS score 0–2) at the time of treatment, the presence of aneurysm-related symptoms, or retreatment rates. Among aneurysms <10 mm, wide-necked aneurysms were more frequent in patients treated with FD than in those treated without FD (81.9% with FD versus 62.8% without FD; P<0.001; Table S1). In patients with FD, dual antiplatelet therapy was administered more frequently, and platinum coil use was less frequent compared with those without FD, regardless of aneurysm size. Technical success rates were >99% irrespective of aneurysm size and FD use, but angiographic complications were less frequent with FD use, both in aneurysms <10 mm (1.1% with FD versus 2.8% without FD; P=0.32) and aneurysms ≥10 mm (1.6% with FD versus 3.2% without FD; P=0.14). The difference in frequency of angiographic complications with and without FD appeared to reflect the lower frequency of aneurysm rupture and distal embolism in patients with FD use compared with those without FD use (Table S1).

Worsening in mRS score ≥1 was seen in a similar frequency for aneurysms <10 mm with FD (2.1%) and without FD (2.0%; P=0.95), and no significant difference in mRS score worsening was observed between patients treated with FD (4.8%) and those without FD (6.1%) for aneurysms ≥10 mm (P=0.44; Figure 2). Ischemic complications were less frequent in patients with FD than in those without FD for aneurysms ≥10 mm (10.1% versus 3.2%; P<0.001), but the difference was not seen for aneurysms <10 mm (3.9% versus 4.3%; P=0.88). The predictive marginal probability of ischemic complications was lower in patients with aneurysms ≥10 mm treated with FD than in those not treated with FD. The difference was not apparent in aneurysms <10 mm (P for interaction=0.03). Hemorrhagic complications were more frequent with FD (4.3%) than without FD (1.5%) in aneurysms <10 mm (P=0.040), and with FD (2.0%) than without FD (0.7%) in aneurysms ≥10 mm (P=0.16). The rate of death within 30 days ranged from 0% to 0.2%, with no significant difference between patients with FD and those without FD, regardless of aneurysm size (Table S2).

Figure 2.

Outcomes by flow diverter (FD) use according to aneurysm sizes. The rate and the probability of worsening in modified Rankin Scale (mRS) score ≥1 (A and B), ischemic complications (C and D), and hemorrhagic complications (E and F) are shown for patients with FD use vs those without, according to aneurysm sizes. The outcome probability was calculated by a logistic model with covariates of age, sex, mRS at the time of endovascular embolization (mRS score 0–2 or mRS score 3–5), the presence or absence of aneurysm symptom, retreatment or first-time treatment, and preprocedural antiplatelet therapy (no antiplatelet agent, single antiplatelet therapy, dual antiplatelet therapy, or triple antiplatelet therapy or more) and a multiplicative term of aneurysm size (<10 mm or ≥10 mm)-by-FD use (with FD or without FD).

In the observation limited to symptomatic aneurysms measuring ≥10 mm, the rate of mRS score worsening was comparable between patients treated with FD (7.9%, 9/114) and those without FD (7.5%, 5/67; P=0.92). Ischemic complications were significantly less frequent with FD (3.5%) than without FD (11.9%; P=0.028). Hemorrhagic complications occurred in 0.9% of patients with FD and 0% of those without (P=0.44), and no deaths were reported in either group.

Further observations by therapeutic modality (coiling without neck-bridging stent, stent-assisted coiling, FD without coiling, and FD with coiling) for aneurysms <10 mm and ≥10 mm are presented separately in Tables S3 and S4. Among aneurysms <10 mm, ischemic complications tended to be more frequent with stent-assisted coiling and FD with coiling, while hemorrhagic complications were observed more often in FD without coiling; however, the sample size of this group was small (N=17). In aneurysms ≥10 mm, outcomes across therapeutic modalities were consistent with the overall analysis.

Discussion

In the present study, we analyzed data of patients with unruptured paraclinoid aneurysms from a nationwide multicenter registry of patients who underwent neuroendovascular therapy in Japan. The study period coincided with the initial adoption of FDs in Japan: FDs were used in 64.2% of patients with aneurysms ≥10 mm, compared with 3.0% in those with <10 mm. The overall morbidity, defined as a worsening in mRS score by ≥1 point at 30 days posttreatment, was comparable to that reported in the earlier studies of endovascular therapy for unruptured intracranial aneurysms in Japan before the introduction of FDs.¹⁹ Patients with aneurysms ≥10 mm had approximately a 2-fold increased risk of morbidity compared with those with aneurysms <10 mm. Although the risk of ischemic complications was higher in the ≥10 mm group, this association lost statistical significance after multivariable adjustment. When stratified by FD use, ischemic complications were less frequent in patients with FD than in those without FD for aneurysm size ≥10 mm. There was no significant difference in 30-day morbidity between patients treated with FD and those treated without FD, regardless of aneurysm size.

Paraclinoid aneurysms account for ≈30% of unruptured intracranial aneurysms treated with endovascular embolization.¹⁹ Large or giant paraclinoid aneurysms carry a significant risk of rupture and are often associated with cranial nerve dysfunction, making them an important target for endovascular therapy.^4–6 In the present study, the morbidity was 5.3% in patients with aneurysms ≥10 mm. Notably, symptomatic aneurysms at baseline were significantly more common among patients who experienced worsening of the mRS score, suggesting that compression-related symptoms may have contributed to the observed morbidity. In a report of 17 patients with unruptured ophthalmic segment aneurysms presenting with anterior optic pathway compression, vision worsened in 38% of cases after endosaccular coiling.⁵ Flow diversion helps to avoid the mass effect associated with endosaccular coiling and potentially facilitates symptom improvement. However, in our study, FD use was not associated with a significant reduction in the 30-day morbidity among patients with aneurysms ≥10 mm. Another study reported symptom improvement or resolution in 79% of patients with cranial nerve dysfunction after FD treatment for paraclinoid or cavernous aneurysms, with a mean follow-up of 39 months; however, transient symptom worsening has also been observed in 24.6% of patients, particularly within the first 3 months posttreatment.⁶ Given that the present study evaluated functional outcomes at 30 days, the follow-up period may have been too short to capture the longer-term benefits of FD use for large or giant aneurysms. In our study, platinum coils were used in 96.9% of FD-treated aneurysms ≥10 mm. However, due to reimbursement constraints under the Japanese healthcare system, sparse coil packing was likely performed in many of these FD-treated cases.^20,21

In this study, FD use in patients with paraclinoid aneurysms ≥10 mm was associated with a significantly lower risk of ischemic complications compared with those treated without FDs. Endosaccular coiling of large or giant aneurysms often requires adjunctive techniques such as neck-bridging stents and deployment of a large number of coils, resulting in meticulous maneuver and prolonged procedure time. Prior studies have shown that ischemic complications increase in endosaccular coiling of larger aneurysms, and this trend has also been observed in paraclinoid aneurysms.^19,22 Given that flow diversion may streamline the procedure and shorten procedure time, it is plausible that these technical advantages contributed to the lower risk of ischemic complications in aneurysms ≥10 mm treated with FDs.²³ However, most ischemic complications in this study did not lead to 30-day morbidity, and the reduction in ischemic complications associated with FD use did not translate into a significant decrease in morbidity in patients with aneurysms ≥10 mm. Furthermore, patients treated with FDs were likely to have received more intensive antiplatelet therapy, which may have contributed to the lower ischemic complication rate but could also explain the observed trend toward increased hemorrhagic complications in this patient group. However, the follow-up period in this study was too short to assess the optimal duration of antiplatelet therapy. A randomized controlled trial is currently underway in Japan (APT-ANswer study [Antiplatelet Therapy in Endovascular Treatment for Cerebral Aneurysms With Flow Diverter], https://jrct.mhlw.go.jp/; Unique identifier: jRCTs041230124) to determine the optimal duration of dual antiplatelet therapy after FD placement.

In aneurysms <10 mm, FD use was limited. Although wide-necked aneurysms were more frequent among <10 mm aneurysms treated with FD, detailed morphological information beyond neck configuration (eg, saccular, fusiform, multilobular) was not available in this registry, and thus, the reasons for FD use in small aneurysms could not be fully elucidated. The rate of hemorrhagic complications appeared numerically higher in aneurysms <10 mm treated with FD without coiling; however, given the small sample size of this subgroup, this finding should be interpreted with caution and may reflect random variation rather than a consistent association.

This study has several limitations. First, as a retrospective observational study, the present study is inherently hypothesis-generating and subject to potential selection and information biases; in addition, multiple analyses were performed without formal correction for multiple hypothesis testing, and thus the findings should be interpreted cautiously. Second, the follow-up period was limited to 30 days, which precludes assessment of long-term functional outcomes. In particular, the potential benefits of FD treatment on symptoms related to mass effect or cranial nerve palsies may not be adequately observed within this short time frame. Moreover, because information on non-neurological or systemic complications was not comprehensively available, the mechanisms underlying 30-day mRS score worsening could not be fully characterized. Future studies with longer-term follow-up are warranted to fully evaluate the therapeutic value of FDs in patients with large or giant paraclinoid aneurysms. Third, the assessment of aneurysm occlusion was limited, as the O’Kelly Marotta grading scale was not used, and the follow-up period was restricted to 30 days.²⁴ As a result, the precision of anatomic outcome assessment remains uncertain, particularly in cases treated with FDs. Lastly, because this study was conducted in a Japanese population, the generalizability of the findings to other ethnic or geographic populations remains uncertain.

Conclusions

Based on data from a nationwide registry, unruptured paraclinoid aneurysms ≥10 mm were associated with a higher risk of functional worsening at 30 days after endovascular therapy. Although FD use significantly reduced ischemic complications in these larger aneurysms, this benefit did not translate into improvement in the 30-day morbidity. Given the potential for delayed symptom improvement with FD use, longer-term follow-up is needed to fully evaluate its therapeutic impact.

ARTICLE INFORMATION

Acknowledgments

The authors thank the JR-NET4 (Japanese Registry of Neuroendovascular Therapy 4) Investigators and certified specialists of the Japanese Society for Neuroendovascular Therapy.

Author Contributions

Dr Fujishima contributed to conceptualization, investigation, methodology, and writing the original draft. Dr Tanaka contributed to conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, visualization, and writing the original draft. Dr Satow contributed to conceptualization, data curation, investigation, resources, supervision, validation, writing—review, and editing. Dr Fujinaka contributed to resources and supervision. Dr Asai contributed to resources, supervision, and writing—review and editing. Dr Ozaki contributed to resources, supervision, and writing—review and editing. Dr Takahashi contributed to resources, supervision. Drs Iihara, Imamura, Ishii, Matsumaru, and Yoshimura contributed to project administration and supervision. C. Sakai contributed to project administration, supervision, and writing—review and editing. N. Sakai contributed to conceptualization, funding acquisition, project administration, resources, and supervision.

Sources of Funding

This study was supported by a research grant from the Japanese Society of Neuroendovascular Therapy, the Kobayashi Foundation, and the Japan Society for the Promotion of Science (Grants-in-Aid for Scientific Research 23K14790).

Disclosures

Dr Tanaka received lecturer fees from Stryker, Daiichi Sankyo, Eisai, and Boston Scientific. Dr Satow received a research grant from CANON Medical Systems, lecturer fees from Medtronic, and consulting fees from Kaneka. Dr Fujinaka received lecturer fees from Medtronic, Stryker, Kaneka, and Terumo, and consulting fees from Stryker. Dr Asai received lecturer fees from Medtronic. Dr Iihara received a research grant from Idorsia Pharmaceuticals Japan outside the submitted work. Dr Imamura reports a lecturer’s fee from Medtronic, Daiichi Sankyo, Stryker, Terumo, and Johnson & Johnson. Dr Ishii received a research grant from Fujifilm and lecturer fees from Medtronic, Stryker, Terumo, Terumo Neuro, Kaneka, Century Medical, Philips Japan, Asahi Intec, Medikit, Daiichi Sankyo, and Johnson & Johnson. Dr Matsumaru reports lecturer fees from Medtronic, Stryker, Terumo, Kaneka, Biomedical Solution, E.P. Medical, B. Braun, Daiichi Sankyo, and Idorsia Pharmaceuticals Japan outside the submitted work. Dr Yoshimura reports research grants from Medico’s Hirata, Medtronic, and Terumo, and lecturer fees from Medtronic Kaneka, Stryker, Daiichi Sankyo, Bristol Myers Squibb, and Johnson & Johnson. N. Sakai reports a research grant from Japan Lifeline, Kaneka, Medtronic, Terumo, and TG Medical; lecturer fees from Asahi Intecc, Kaneka, Medtronic, Stryker, and Terumo; and membership on the advisory boards of Johnson & Johnson, Medtronic, and Terumo outside the submitted work. The other authors report no conflicts.

Supplemental Material

Tables S1–S4

Figure S1

STROBE Checklist

Supplementary Material

svi2-6-e002039-s001.pdf ^{(331.1KB, pdf)}

svi2-6-e002039-s002.pdf ^{(117.8KB, pdf)}