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Abstract
Background Coiling, including balloon-assisted coiling (BAC), is the first-line therapy for ruptured and unruptured aneurysms. Its efficacy can be clinically evaluated by bleeding/rebleeding rate after coiling, and anatomically evaluated by aneurysm occlusion post-procedure and during follow-up. We aimed to analyze immediate post-coiling aneurysm occlusion and associated factors within the Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm (ARETA) population.
Methods Between December 2013 and May 2015, 16 neurointerventional departments prospectively enrolled participants treated for ruptured and unruptured aneurysms (ClinicalTrials.gov: NCT01942512). Participant demographics, aneurysm characteristics, and endovascular techniques were recorded. In patients with aneurysms treated by coiling or BAC, immediate post-operative aneurysm occlusion was independently evaluated by a core lab using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant.
Results Of 1135 participants (age 53.8±12.8 years, 754 women (66.4%)), 1189 aneurysms were analyzed. Treatment modality was standard coiling in 645/1189 aneurysms (54.2%) and BAC in 544/1189 (45.8%). Immediate post-operative aneurysm occlusion was complete occlusion in 57.8%, neck remnant in 34.4%, and aneurysm remnant in 7.8%. Adequate occlusion (complete occlusion or neck remnant) was significantly more frequent in aneurysms with size <10 mm (93.1% vs 86.3%; OR 1.8, 95% CI 1.1 to 3.2; p=0.02) and in aneurysms with a narrow neck (95.8% vs 89.6%; OR 2.5, 95% CI 1.5 to 4.1; p=0.0004). Patients aged <70 years had significantly more adequate occlusion (92.7% vs 87.2%; OR 1.9, 95% CI 1.1 to 3.4; p=0.04).
Conclusions Immediately after aneurysm coiling, including BAC, adequate aneurysm occlusion was obtained in 92.2%. Age <70 years, aneurysm size <10 mm, and narrow neck were factors associated with adequate occlusion.
Trial registration number NCT01942512, http://www.clinicaltrials.gov.
- aneurysm
- coil
Data availability statement
Data are available upon reasonable request. Data analyzed during the study are available from the corresponding author by request.
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Introduction
Endovascular treatment (EVT) is the first-line therapy in the management of intracranial aneurysm (IA) in France; several techniques are available including coiling, balloon-assisted coiling (BAC), stent-assisted coiling (SAC), flow diversion, and flow disruption.1 Despite the increasing use of flow diversion and flow disruption, coiling and BAC remain the most frequently used endovascular techniques.2 A primary limitation of these techniques is a relatively high rate of aneurysm recanalization related to coil compression or aneurysm regrowth.3 4 Analyzing the frequency and factors associated with aneurysm recanalization is important in order to reduce occurrence and further optimize EVT.
The Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm (ARETA) study is a publicly funded, multicenter, prospective French study analyzing patient, aneurysm, and technical factors that affect aneurysm recanalization after EVT.3 Between December 2013 and May 2015, a large cohort of 1289 participants with ruptured or unruptured aneurysms undergoing EVT were enrolled in 16 neurointerventional centers. Determining the rates and factors associated with immediate post-operative aneurysm occlusion is an important step, prior to exploring rates and predictors of aneurysm recanalization. As the literature clearly demonstrates that indications are different and stable aneurysm occlusion occurs in a different time frame after flow disruption, flow diversion, and aneurysm coiling (including BAC), post-operative aneurysm occlusion has to be analyzed separately according to the different EVT techniques.1
The present analysis aims to describe the rate of immediate post-operative IA occlusion after coiling (including BAC) and associated patient and aneurysm factors.
Participants and methods
The ARETA study
ARETA was sponsored and entirely funded by the French Ministry of Health in a PHRC (Programme Hospitalier de Recherche Clinique, No. 12-001-0372) and registered on www.clinicaltrials.gov (NCT01942512). ARETA received national regulatory authorization approval from the Consultative Committee of Information Processing in Healthcare Research Program and the National Commission for Data Processing and Freedom. According to French law, the study design did not require Institutional Review Board approval or written informed consent.
ARETA was designed to evaluate factors affecting aneurysm recanalization after EVT. The study objective and its protocol, including inclusion and exclusion criteria, have previously been described.3 The full study protocol and data generated or analyzed during ARETA are available by request from the corresponding author.
Inclusion criteria were 18+ years, saccular IA, ruptured or unruptured, and treated by EVT. Patients treated by surgery were not part of the ARETA study and were not included. Exclusion criteria were dissecting or fusiform aneurysms, aneurysms associated with a brain arteriovenous malformation (AVM), aneurysms already treated by clips or coils, previous treatment for another aneurysm, and patients protected by law.
Sample size was calculated to evaluate a potential association between tobacco use and recanalization at 12 months. Estimating tobacco use in 40% of participants without recanalization and 55% with recanalization, a recanalization rate of 25% with an alpha of 5%, power of 95%, and a two-sided test, 760 participants were required (NQuery version 4.0, Cork, Ireland).3 Given an estimated 40% rate of loss to follow-up or death at 12 months, a sample size of 1275 participants was necessary.
Between December 2013 and May 2015, participants were prospectively enrolled (convenience sampling) in 16 French centers. Baseline participant characteristics reported by the participating study sites included: age; sex; body mass index; current use of cigarettes, alcohol, and cannabis; elevated blood pressure (defined as blood pressure >140/90 mmHg uncorrected by medical treatment); hypercholesterolemia (defined as total cholesterol >5.5 mmol/L uncorrected by medical treatment) and hypertriglyceridemia (triglycerides >1.7 mmol/L uncorrected by medical treatment); diabetes mellitus (glycemia >6 mmol/L); polycystic kidney disease; and familial aneurysm history. Familial aneurysm history was defined as the presence of two or more family members among first- and second-degree relatives with proven aneurysmal subarachnoid hemorrhage or incidental aneurysms.
Recorded aneurysm characteristics were aneurysm rupture status (ruptured/unruptured); aneurysm sac maximum diameter (dichotomized into <10 mm and ≥10 mm); neck size (dichotomized into <4 mm and ≥4 mm; wide neck being defined as neck ≥4 mm and/or dome-to-neck ratio <2); aneurysm location (extradural internal carotid artery (ICA), intradural ICA including the posterior communicating artery, middle cerebral artery (MCA), anterior communicating/anterior cerebral artery (ACA/Acom), or vertebrobasilar (VB)); aneurysm morphology (regular or irregular); and number of IAs (single or multiple). Aneurysms were classified as regular when there was a single sac with smooth margin, and irregular if it was a single sac with irregular margin or a daughter sac or a multilobulated aneurysm.
Treating interventional neuroradiologists autonomously chose treatment modalities, which we categorized into coils, BAC, SAC, flow diversion, intrasaccular flow-disruption, and parent vessel sacrifice. Pre-operative antiplatelet treatment and intra-operative heparin treatment were also collected.
Six ARETA publications have been previously published, including one describing background and protocol, one describing population and modalities of treatment, one analyzing patient and aneurysm risk factors associated with aneurysm rupture, one analyzing intra-operative complications during aneurysm coiling (or BAC), one analyzing delayed aneurysm rupture after aneurysm coiling (including BAC), and one analyzing delayed thromboembolic events after aneurysm coiling or BAC.2 3 5–8
Data management
Participating centers reported participant, aneurysm, and treatment characteristics on a standardized form. Centers also collected pre-operative digital subtraction angiography (DSA) and immediate post-operative DSA and transferred anonymized results to Reims Hospital. Aneurysm characteristics and treatment modalities were reviewed, checked for accuracy and, if necessary, revised by a core lab (LS and PW). The core lab also independently evaluated immediate post-operative aneurysm occlusion using a 3-grade scale: complete aneurysm occlusion, neck remnant, and aneurysm remnant. Adequate occlusion was defined as complete occlusion or neck remnant.
To analyze the treatment strategy (BAC/coiling) in the different participating centers, they were dichotomized into two groups (according to the mean percentage of BAC in the population of aneurysms treated with coiling or BAC, 45.8%): centers in which >45.8% of aneurysms were treated using BAC, and centers in which <45.8% of aneurysms were treated using BAC.
Participants treated with a technique other than coiling or BAC (SAC, flow diversion, flow disruption) were excluded from this analysis.
Statistical analysis
Given that the study objective was to identify patient and aneurysm factors associated with adequate occlusion, and that some patients had treatment for multiple aneurysms, we conducted two different analyses. First, we conducted univariate and multivariate analyses in patients with treatment of a unique aneurysm population to determine patient factors associated with adequate occlusion. Second, we conducted univariate and multivariate analyses in the overall aneurysm population to determine aneurysm factors associated with adequate occlusion.
Data were presented using mean±SD for continuous variables and number and percentage for categorical variables. Patient and aneurysm factors associated with adequate occlusion were studied using univariate analysis (Student’s t test, χ2 test or Fisher exact test, as appropriate) and multivariate analysis (logistic regressions with stepwise selection, with an exit threshold of 0.20 and factors significant at p=0.10 included). Treated aneurysm characteristics and patient characteristics were compared between centers treating less and more than 45.8% of aneurysms with BAC using univariate analyses (Student t test, χ2 test or Fisher exact test, as appropriate) and multivariate analyses (logistic regressions with stepwise selection, with an exit threshold of 0.20 and factors significant at p=0.10 included). A p value <0.05 was considered statistically significant. All analyses were performed using SAS version 9.4 (SAS Institute Inc, Cary, North Carolina, USA).
Results
Study population, participant and aneurysm characteristics, and treatment modalities
After applying inclusion criteria to the overall cohort of 1289 participants harboring 1761 aneurysms, 1135 participants (age 53.8±12.8 years, 754 women (66.4%)) with 1189 aneurysms were included in the study population for this analysis (figure 1). The number of patients/aneurysms treated with other EVT techniques is reported in figure 1. Table 1 details additional participant characteristics and table 2 presents aneurysm characteristics. Treatment modality was standard coiling in 645/1189 aneurysms (54.2%) and BAC in 544/1189 aneurysms (45.8%). BAC was heterogeneously used from one center to another (13.1% to 94.4% were treated with BAC according to the center, mean 45.8%). Analyzing the patient population, there is no significant difference in patient characteristics in centers using more or less than 45.8% BAC (online supplemental table 1). Analyzing the aneurysm population, in the centers using BAC in more than 45.8%, treated aneurysms had a wide neck significantly less often (52.4% vs 62.1%; p=0.002) and tended to be ruptured significantly more often (72.1% vs 65.8%; p=0.05) (online supplemental table 2).
Supplemental material
Supplemental material
ARETA patient characteristics treated with coiling or balloon-assisted coiling and ARETA patients treated for a unique aneurysm during the index procedure
Aneurysm characteristics in ARETA patients treated with coiling or balloon-assisted coiling
Flow chart of the study population. 1IA, intracranial aneurysm; 2DSA, digital subtraction angiography.
Status of immediate post-operative occlusion
In the global population, immediate post-operative occlusion was complete occlusion in 687/1189 aneurysms (57.8%), neck remnant in 409/1189 (34.4%), and aneurysm remnant in 93/1189 (7.8%) (figure 2). Adequate occlusion was obtained in 1096/1189 aneurysms (92.2%).
A–C: Anterior communicating aneurysm. A: before coiling; B: coils in the sac; C: after coiling: complete occlusion. D–F: Anterior communicating aneurysm. D: before coiling; E: coils in the sac; F: after coiling: neck remnant. G–I: Basilar artery aneurysm. G: before coiling; H: coils in the sac; I: after coiling: aneurysm remnant (residual opacification in the coil mesh in the left part of the aneurysm sac).
In ruptured aneurysms, immediate post-operative occlusion was complete occlusion in 465/813 aneurysms (57.2%), neck remnant in 290/813 (35.7%), and aneurysm remnant in 58/813 (7.1%). Adequate occlusion was obtained in 755/813 aneurysms (92.9%).
In unruptured aneurysms, immediate post-operative occlusion was complete occlusion in 222/376 aneurysms (59.0%), neck remnant in 119/376 (31.7%), and aneurysm remnant in 35/376 (9.3%). Adequate occlusion was obtained in 341/376 aneurysms (90.7%).
Patient factors associated with adequate occlusion
Only one patient factor associated with adequate occlusion was identified in univariate analysis: age (<70 years 92.7%; ≥70 years 87.2%; p=0.04) (table 3). No significant associations were found between adequate occlusion and sex (p=0.61), elevated blood pressure (p=0.92), hypercholesterolemia (p=0.54), hypertriglyceridemia (p=0.39), diabetes mellitus (p=0.61), current smoking (p=0.22), regular alcohol consumption (p=0.11), polycystic kidney disease (p=0.62), and family history (p=0.37).
Univariate analysis of patient factors associated with immediate post-operative adequate aneurysm occlusion.
As only one patient factor was identified by univariate analysis, no multivariate analysis was conducted.
Aneurysm factors associated with adequate occlusion
In univariate analysis, two factors were associated with adequate occlusion: adequate occlusion was more frequent in IA with a maximum diameter <10 mm (93.1% vs 86.3% in aneurysm ≥10 mm; p=0.003) and in narrow neck aneurysms (95.8% vs 89.6% in wide neck aneurysms; p<0.0001) (table 4). These two factors were also significant in the multivariate analysis: aneurysm maximum diameter (p=0.02) and wide neck (p=0.0004).
Univariate and multivariate analysis of aneurysm factors associated with immediate post-operative adequate aneurysm occlusion
Aneurysm rupture status (ruptured 92.9%; unruptured 90.7%; p=0.19) and treatment technique (coiling 91.8%; BAC 92.7%; p=0.58) were not associated with adequate occlusion.
Discussion
Our analysis of the ARETA population showed that immediate post-operative aneurysm occlusion resulted in complete occlusion in 57.8%, neck remnant in 34.4%, and aneurysm remnant in 7.8%, with adequate occlusion (complete occlusion or neck remnant) in 92.2%. One patient factor (age <70 years) and two aneurysm factors (aneurysm size <10 mm, and narrow neck) were associated with adequate occlusion.
Since the initial International Subarachnoid Trial (ISAT) publication, the efficacy of EVT of intracranial aneurysms has been a matter for debate.9 EVT therapy can be evaluated in two ways: clinically, by evaluating the rate of rebleeding (for ruptured aneurysms) and bleeding (for unruptured aneurysms), and anatomically, by evaluating aneurysm occlusion post-procedure and during follow-up. Clinical evaluation in the ARETA population has previously shown 0.0% bleeding in unruptured aneurysms and 1.0% rebleeding in ruptured aneurysms at 1 year follow-up.7
The current analysis demonstrated that immediate post-operative aneurysm occlusion was not significantly different (p=0.19 for adequate occlusion) in both ruptured (complete occlusion in 57.2%, neck remnant in 35.7%, aneurysm remnant in 7.1%, with adequate occlusion in 92.9%) and unruptured aneurysms (complete occlusion in 59.0%, neck remnant in 31.7%, aneurysm remnant in 9.3%, with adequate occlusion in 90.7%). Similar results were reported in a previous series dedicated to unruptured aneurysms (Analysis of Treatment by Endovascular Approach of Nonruptured Aneurysms (ATENA)) and ruptured aneurysms (Clinical and Anatomic Results in the Treatment of Ruptured Intracranial Aneurysms (CLARITY)). In ATENA, immediate post-operative aneurysm occlusion was complete occlusion in 63.0%, neck remnant in 22.5%, and aneurysm remnant in 14.6%, with adequate occlusion in 85.5%. In CLARITY, immediate post-operative aneurysm occlusion was complete occlusion in 47.4%, neck remnant in 41.9%, and aneurysm remnant in 10.7%, with adequate occlusion in 89.3%.
Age lower than 70 years was associated with a higher rate of adequate occlusion than in older patients (92.7% vs 87.2%, p=0.04). Similar results were reported in ATENA with adequate occlusion in patients younger than 65 years in 88.0% and in patients older than 65 in 67.8%, and in CLARITY with adequate occlusion in 90.5% and 82.9%, respectively. These similar findings likely reflect the fact that older patients have more arterial tortuosity and potentially more atherosclerotic lesions. Coiling strategy is also potentially slightly different according to age, as older patients require less packing density compared with younger patients.
Two aneurysm factors were associated with a higher rate of adequate occlusion: small aneurysms (<10 mm) and narrow neck. In small aneurysms, adequate occlusion was observed in 93.1% whereas in larger aneurysms it was 86.3% (univariate p=0.003, multivariate p=0.02). In the CLARITY study, aneurysm size was not depicted as being associated with the postoperative aneurysm acclusion status. 10 In ATENA, where the same limit was implemented, adequate occlusion was also more frequent in small rather than large (87.5% vs 82.6%) aneurysms,11 which is probably related to the fact that it is more difficult to obtain a dense coil packing in large aneurysms than in small ones. The fact that a narrow neck is associated with a higher rate of adequate occlusion is not really surprising as coiling of wide neck aneurysms is technically more difficult. In this series, aneurysms treated with coiling or BAC are mixed; results confirm no difference in terms of aneurysm occlusion in both groups (p=0.58). These findings suggest that aneurysms >10 mm and wide neck aneurysms are relatively difficult to treat with coils, even when using BAC.
In the current analysis, wcoiling alone and BAC were mixed as the final results of the procedure is placement of coils in the aneurysm. It permits to determine if BAC is associated with better anatomical results, which is not the case. BAC is heterogeneously used from one center to another (13.1% to 94.4%, mean 45.8%). In the centers with a high use of BAC (>45.8%), a higher percentage of ruptured aneurysms and narrow neck aneurysms are treated compared with low BAC centers. This probably illustrates the evolution of BAC use, which was initially limited to wide-neck aneurysms in order to avoid coil protrusion, and is now extended to narrow neck ruptured aneurysms, with the balloon being used as a rescue technique in case of intra-operative rupture.12 13
Limitations
Our study has some limitations. First, the reliable collection of a high number of participant characteristics in a large patient population is always challenging, as demonstrated by the relatively large amount of missing data for some participant characteristics. However, to the best of our knowledge, this study includes, for the first time, a large number of patient factors in the analysis of post-operative aneurysm occlusion. Second, immediate post-operative imaging was not included in five patients because it was missing or poor quality. However, the percentage of patients with good quality post-operative imaging is high (1189/1195 aneurysms, 99.5%).
Conclusion
In this series of 1135 patients with 1189 ruptured and unruptured aneurysms treated with coiling or BAC, immediate post-operative imaging evaluated by an independent core lab demonstrated complete aneurysm occlusion in 57.8%, neck remnant in 34.4%, and aneurysm remnant in 7.8% with adequate occlusion in 92.2%. Three factors were associated with adequate occlusion: age <70 years, aneurysm size <10 mm, and narrow neck.
Data availability statement
Data are available upon reasonable request. Data analyzed during the study are available from the corresponding author by request.
Ethics statements
References
Supplementary materials
Supplementary Data
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Footnotes
Contributors All authors have: provided a substantial contribution to the conception and design of the studies and/or the acquisition and/or the analysis of the data and/or the interpretation of the data; drafted the work or revised it for significant intellectual content; approved the final version of the manuscript; and agreed to be accountable for all aspects of the work, including its accuracy and integrity.
Funding The French Health Ministry has funded ARETA (Programme Hospitalier de Recherche Clinique, No. 12-001-0372).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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