Intraoperative Complications of Endovascular Treatment of Intracranial Aneurysms with Coiling or Balloon-assisted Coiling in a Prospective Multicenter Cohort of 1088 Participants: Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm (ARETA) Study

The ARETA Study

ARETA was designed to systematically evaluate factors that affect aneurysm recanalization after endovascular treatment. The study was sponsored and completely funded by the French Ministry of Health in a hospital clinical research program (grant no. 12–001–0372) and registered on https://www.clinicaltrials.gov (NCT01942512). ARETA received national regulatory authorization approval from the Consultative Committee of Information Processing in Health Care Research Program and the National Commission for Data Processing and Freedom. The study objective and its protocol, including inclusion and exclusion criteria, have previously been described (2). The full study protocol is available from the corresponding author by request. Data generated or analyzed during the study are available from the corresponding author by request. By French law, due to the study design, approval by an institutional review board and written informed consent were not necessary.

The following inclusion criteria were used: age older than 18 years, saccular intracranial aneurysm (IA), ruptured or unruptured aneurysm, and aneurysm treated with an endovascular technique. Exclusion criteria were as follows: dissecting or fusiform aneurysms, aneurysms associated with a brain arteriovenous malformation, aneurysms already treated by using clips or coils, previous treatment for another aneurysm, and patients protected by the law (participants who are unable to make decision for themselves due to psychiatric or somatic disturbances).

The sample size was calculated to evaluate a potential association between tobacco use and recanalization at 12 months. Based on estimates of tobacco use in 40% of participants without recanalization and in 55% of participants with recanalization and a recanalization rate of 25%, with an alpha of 5%, a power of 95%, and a two-sided test, the number of participants required was 760 (NQuery software, version 4.0; Cork, Ireland) (3). Given an estimated rate of loss of 40% to follow-up or death at 12 months, we estimated a sample size of 1275 participants was necessary.

Participants were prospectively enrolled (convenience sampling) in 16 centers in France between December 2013 and May 2015. The following baseline participant characteristics were reported by the participating study sites: age; sex; current use of cigarettes, alcohol, and cannabis; elevated blood pressure (defined as blood pressure >140/90 mm Hg uncorrected by medical treatment); hypercholesterolemia (defined as total cholesterol level >5.5 mmol/L uncorrected by medical treatment) and triglyceridemia (triglycerides level >1.7 mmol/L uncorrected by medical treatment); diabetes mellitus (glycemia >6 mmol/L); Ehlers-Danlos syndrome or other connective tissue diseases; polycystic kidney disease; and family history of intracranial aneurysm. Family history of intracranial aneurysm 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. Clinical status before treatment was evaluated with World Federation of Neurosurgical Societies grade for participants with ruptured intracranial aneurysms (RIA) and the preprocedural modified Rankin Scale (mRS) score for participants with unruptured intracranial aneurysms (UIA).

Recorded aneurysm characteristics were aneurysm sac diameter (dichotomized into <5 mm and ≥5 mm); neck size (wide-necked being defined as ≥4 mm); aneurysm location (extradural internal carotid artery [ICA], intradural ICA including the posterior communicating artery, middle cerebral artery, anterior communicating and anterior cerebral artery, or vertebral artery); aneurysm rupture status (ruptured or unruptured); aneurysm morphologic features (regular or irregular); and number of IA (single or multiple). Aneurysm was classified as regular when there was a single sac with smooth margin, and as irregular if it was a single sac with irregular margin, a daughter sac, or a multilobulated aneurysm.

Treatment modalities were at the discretion of the treating interventional neuroradiologist and categorized into coiling, BAC, stent-assisted coiling, flow diversion, intrasaccular flow disruption, and parent vessel sacrifice. Data on preoperative antiplatelet treatment and intraoperative heparin treatment were also collected.

Data Management

Participating centers reported participant, aneurysm, and treatment characteristics and complications on a standardized form. Thromboembolic events were diagnosed intraoperatively by using angiography regardless of type (clotting near the neck of the aneurysm or in distal branches and parent vessel occlusion). Intraoperative rupture was diagnosed by the exit of the tip of the microguidewire, the microcatheter, or the coil outside the limit of the aneurysmal sac and/or extravasation of contrast media and/or sudden modification of hemodynamic parameters with elevation of blood pressure. Clinical outcome was evaluated by using mRS score at hospital discharge. Poor clinical outcome was defined by mRS score of 3–6 at hospital discharge.

The centers also collected preoperative digital subtraction angiography and immediate postoperative digital subtraction angiography and transferred results in an anonymized form to Reims Hospital (Reims, France). Aneurysm characteristics, treatment modalities, and complications of all participants were reviewed, checked for accuracy, and (if necessary) revised by two neuroradiologists (M.G. and S.S., with 5 years and 7 years of experience in neuroradiology, respectively).

Study Participants

The following participants within the overall ARETA cohort were excluded from our analysis: participants treated with a technique other than coiling or BAC (ie, stent-assisted coiling, flow diversion, flow disruption) and participants treated for multiple aneurysms in the same procedure. The reason for this exclusion criterion was that one of the goals of our study was to conduct an analysis of factors affecting the occurrence of complications. When participants are treated for multiple aneurysms in the same session, it can be difficult to identify the aneurysm responsible for a TEE.

Three ARETA articles have been previously published. One described the background and protocol (15). The two others analyzed the same cohort with topics that were completely different: One article described the population and modalities of treatment, and one article analyzed patient and aneurysm risk factors associated with aneurysm rupture (2,16).

Statistical Analysis

Data management and statistical analysis were conducted by the Department of Research and Public Health of Reims Hospital. Descriptive statistics were applied: data are presented as means ± standard deviation for quantitative variables and numbers and percentages for qualitative variables. Factors associated with IOR and TEE were studied by using univariable analyses (Student t tests, χ² tests, or Fisher exact tests, as appropriate) and multivariable analyses (logistic regressions with stepwise selection, with entry and removal limits set at 0.20 and factors significant at P = .20 included). A P value of < .05 was considered to indicate statistical significance. Statistical analysis was performed by using SAS (version 9.4; SAS Institute, Cary, NC).

Study Population, Participant and Aneurysm Characteristics, and Treatment Modalities

Following the application of our inclusion criteria to the overall cohort of 1289 participants (harboring 1761 aneurysms), the study population for this analysis consisted of 1088 participants (mean age ± standard deviation, 54 years ± 13; 715 women [65.7%]) with 1088 aneurysms (Figure). Mean age was 54 years ± 13 (range, 23–86 years) for female participants and 53 years ± 13 (range, 19–92 years) for male participants. Table 1 details additional participant characteristics and Table 2 presents the aneurysm characteristics. Treatment modality was standard coiling in 596 of 1088 participants (54.8%) and BAC in 492 of 1088 participants (45.2%).

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Table 1: Participant Characteristics

Table 2: Aneurysm Characteristics

Rate and Clinical Outcome of Thromboembolic Events

TEEs were reported in 113 of 1088 participants (10.4%). For participants with TEE, mRS score at hospital discharge was 0–2 in 84 of 113 participants (74.3%), 3–5 in 24 of 113 participants (21.2%), and 6 (mortality) in five of 113 participants (4.4%). Poor clinical outcome (mRS score of 3–6) was observed in 29 of 113 participants with TEE (25.7%). In the whole cohort, the rate of TEE with poor clinical outcome was 29 of 1083 participants (2.7%) with mRS score known at hospital discharge.

TEEs were reported in 78 of 753 participants (10.4%) treated for RIA. In participants with RIA and TEE, mRS score at hospital discharge was 0–2 in 52 of 78 participants (66.7%), 3–5 in 22 of 78 participants (28.2%), and 6 (mortality) in four of 78 participants (5.1%). Poor clinical outcome was observed in 26 of 78 participants with RIA and TEE (33.3%). In the whole RIA cohort, the rate of TEE with poor clinical outcome was 26 of 748 participants (3.5%) with mRS score known at hospital discharge.

TEEs were reported in 35 of 335 participants treated for UIA (10.4%). In participants with UIA and TEE, mRS score at hospital discharge was 0–2 in 32 of 35 participants (91.4%), 3–5 in two of 35 participants (5.7%), and 6 (mortality) in one of 35 participants (2.9%). Poor clinical outcome was observed in three of 35 participants with UIA and TEE (8.6%). In the whole UIA cohort, the rate of TEE with poor clinical outcome was three of 335 participants (0.9%) with mRS score known at hospital discharge.

Rate and Clinical Outcome of Intraoperative Rupture

IOR was reported in 34 of 1088 participants (3.1%). For participants with IOR, mRS score at hospital discharge was 0–2 in 23 of 34 participants (67.6%), 3–5 in six of 34 participants (17.6%), and 6 (mortality) in five of 34 participants (14.7%). Poor clinical outcome was observed in 11 of 34 participants with IOR (32.4%). In the whole cohort, the rate of IOR with poor clinical outcome was 11 of 1083 participants (1.0%) with mRS score known at hospital discharge.

IOR was reported in 28 of 753 participants treated for RIA (3.7%). In participants with RIA and IOR, mRS score at hospital discharge was 0–2 in 18 of 28 participants (64.3%), 3–5 in six of 28 participants (21.4%), and 6 (mortality) in four of 28 participants (14.3%). Poor clinical outcome was observed in 10 of 28 participants with RIA and IOR (35.7%). In the whole RIA cohort, the rate of IOR with poor clinical outcome was 10 of 748 participants (1.0%) with mRS score known at hospital discharge.

IOR was reported in six of 335 participants treated for UIA (1.8%). In participants with UIA and IOR, mRS score at hospital discharge was 0–1 in five of six participants (83.3%), 3–5 in zero of six participants, and 6 (mortality) in one of six participants (16.7%). Poor clinical outcome was observed in one of six participants with UIA and IOR (16.7%). In the whole UIA cohort, the rate of IOR with poor clinical outcome was one of 335 participants (0.3%) with mRS score known at hospital discharge.

Rate of poor clinical outcome (mRS score of 3–6) was not significantly different between participants with TEE and participants with IOR (29 of 113 participants with TEE, 25.7% vs 11 of 34 participants with IOR, 32.4%; P = .44).

Factors Associated with Thromboembolic Events

In univariable analysis, three factors were associated with TEE. TEE was more frequent in IA located in the middle cerebral artery (41 of 221 participants, 18.5% vs 72 of 867 participants, 8.3% in other locations; P < .001) and in women (84 of 715 participants, 11.7% vs 29 of 373 participants, 7.8% in men; P = .04), and TEE was less frequent in IA located in the intradural ICA (21 of 338 participants, 6.2% vs 92 of 750 participants, 12.3% in other locations; P = .002) (Table 3).

Table 3: Factors Affecting Thromboembolic Event Occurrence

In the multivariable analysis, two risk factors for TEE were identified: middle cerebral artery location (odds ratio [OR], 1.9; 95% confidence interval [CI]: 1.2, 3.0; P = .008) and female sex (OR, 1.7; 95% CI: 1.1, 2.8; P = .02). One protective factor for TEE was identified: ICA intradural location (OR, 0.5; 95% CI: 0.3, 0.8; P = .01).

Factors Associated with Intraoperative Rupture

In univariable analysis, four factors were associated with IOR. IOR was more frequent in IA smaller than 5 mm in diameter and in IA located in the anterior cerebral or communicating artery (20 of 322 participants, 6.2% vs 14 of 766 participants, 1.8%; P < .001 and 20 of 439 participants, 4.6% vs 14 of 649 participants, 2.2%; P = .03, respectively). Neck size was smaller in IA with IOR (2.6 mm ± 1.1 vs 3.3 mm ± 1.5; P = .006), and IOR was less frequent in participants with regular alcohol consumption (two of 227 participants, 0.9% vs 30 of 839 participants, 3.6%; P = .03) (Table 4).

Table 4: Factors Affecting Intraoperative Rupture Occurrence

In the multivariable analysis, two risk factors of IOR were identified: aneurysm size less than 5 mm (OR, 3.0; 95% CI: 1.5, 6.3; P = .003) and the anterior cerebral or communicating artery location (OR, 2.2; 95% CI: 1.1, 4.7; P = .03).