Endovascular Treatment of Intracranial Unruptured Aneurysms: A Systematic Review of the Literature on Safety with Emphasis on Subgroup Analyses

Published Online:https://doi.org/10.1148/radiol.12112114

Use of remodeling techniques did not increase the risk of unfavorable outcome, whereas use of flow-diverter devices is associated with a risk of unfavorable outcome that is twice the risk of simple coil placement.


To report subgroup analyses of an updated systematic review on endovascular treatment of intracranial unruptured aneurysms (UAs); to compare types of embolic agents, adjunct techniques, and newer devices; and to identify potential risk factors for poor outcomes.

Materials and Methods

Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to prepare this article, and the literature was searched with PubMed and with EMBASE and Cochrane databases. Six eligibility criteria (procedural complications rates; at least 10 patients; saccular, nondissecting UAs; original study published in English or French between January 2003 and July 2011; methodological quality score > 6 [modified Strengthening and Reporting of Observational Studies in Epidemiology criteria]; a study published in a peer-reviewed journal) were used. End points included procedural mortality and unfavorable outcomes (death or modified Rankin Scale, Glasgow Outcome Scale, or World Federation of Neurosurgeons Scale at 1 month scores, all > 2). A fixed-effects model (Mantel-Haenszel) was used for pooled estimates of mortality and unfavorable outcomes; a random-effects model (DerSimonian-Laird) was used in case of heterogeneity.


Ninety-seven studies with 7172 patients (26 studies published July 2008 through July 2011) were included. Sixty-nine (1.8%) of 7034 patients died (fixed-effect weighted average; 99% confidence interval [CI]: 1.4%, 2.4%; Q value, 55.0; I2 = 0%). Unfavorable outcomes, including death, occurred in 4.7% (242 of 6941) of patients (99% CI: 3.8, 5.7; Q value, 128.3; I2 = 26.8%). Patients treated after 2004 had better outcomes (unfavorable outcome, 3.1; 99% CI: 2.4, 4.0) than patients treated during 2001–2003 (unfavorable outcome, 4.7%; 99% CI: 3.6%, 6.1%; P = .01) or in 2000 and before (unfavorable outcome, 5.6%; 99% CI: 4.7%, 6.6%; P < .001). Significantly higher risk was associated with liquid embolic agents (8.1%; 99% CI: 4.7%, 13.7%) versus simple coil placement (4.9%; 99% CI: 3.8%, 6.3%; P = .002). Unfavorable outcomes occurred in 11.5% (99% CI: 4.9%, 24.6%) of patients treated with flow diversion.


Procedure-related poor outcomes occurred (4.7% of patients), risks decreased, and liquid embolic agents and flow diversion were associated with higher risks.

©RSNA, 2012

Supplemental material:http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112114/-/DC1


  • 1 Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol 2011;10(7):626–636. Crossref, MedlineGoogle Scholar
  • 2 Cowan JA, Ziewacz J, Dimick JB, Upchurch GR, Thompson BG. Use of endovascular coil embolization and surgical clip occlusion for cerebral artery aneurysms. J Neurosurg 2007;107(3):530–535. Crossref, MedlineGoogle Scholar
  • 3 Raymond J, Guilbert F, Weill A, Roy D. Unruptured intracranial aneurysms: a call for a randomized clinical trial. AJNR Am J Neuroradiol 2006;27(2):242–243. MedlineGoogle Scholar
  • 4 Naggara ON, White PM, Guilbert F, Roy D, Weill A, Raymond J. Endovascular treatment of intracranial unruptured aneurysms: systematic review and meta-analysis of the literature on safety and efficacy. Radiology 2010;256(3):887–897. LinkGoogle Scholar
  • 5 von Elm E, Altman DG, Egger M, et al.. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007;370(9596):1453–1457. Crossref, MedlineGoogle Scholar
  • 6 Kasner SE. Clinical interpretation and use of stroke scales. Lancet Neurol 2006;5(7):603–612. Crossref, MedlineGoogle Scholar
  • 7 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21(11):1539–1558. Crossref, MedlineGoogle Scholar
  • 8 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557–560. Crossref, MedlineGoogle Scholar
  • 9 Wiebers DO, Whisnant JP, Huston J, et al.. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362(9378):103–110. Crossref, MedlineGoogle Scholar
  • 10 Lanzino G, Rabinstein AA. Aneurysmal subarachnoid hemorrhage in the elderly. J Neurosurg 2010;112(6):1197–1198; discussion 1198–1199. Crossref, MedlineGoogle Scholar
  • 11 Pierot L, Spelle L, Vitry F; ATENA investigators. Immediate clinical outcome of patients harboring unruptured intracranial aneurysms treated by endovascular approach: results of the ATENA study. Stroke 2008;39(9):2497–2504. Crossref, MedlineGoogle Scholar
  • 12 Alshekhlee A, Mehta S, Edgell RC, et al.. Hospital mortality and complications of electively clipped or coiled unruptured intracranial aneurysm. Stroke 2010;41(7):1471–1476. Crossref, MedlineGoogle Scholar
  • 13 Piotin M, Blanc R, Spelle L, et al.. Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 2010;41(1):110–115. Crossref, MedlineGoogle Scholar
  • 14 Moret J, Cognard C, Weill A, Castaings L, Rey A. The “remodelling technique” in the treatment of wide neck intracranial aneurysms: angiographic results and clinical follow-up in 56 cases. Interv Neuroradiol 1997;3(1):21–35. Crossref, MedlineGoogle Scholar
  • 15 Sluzewski M, van Rooij WJ, Beute GN, Nijssen PC. Balloon-assisted coil embolization of intracranial aneurysms: incidence, complications, and angiography results. J Neurosurg 2006;105(3):396–399. Crossref, MedlineGoogle Scholar
  • 16 Pierot L, Cognard C, Anxionnat R, Ricolfi F; CLARITY investigators. Remodeling technique for endovascular treatment of ruptured intracranial aneurysms had a higher rate of adequate postoperative occlusion than did conventional coil embolization with comparable safety. Radiology 2011;258(2):546–553. LinkGoogle Scholar
  • 17 Kulcsár Z, Ernemann U, Wetzel SG, et al.. High-profile flow diverter (silk) implantation in the basilar artery: efficacy in the treatment of aneurysms and the role of the perforators. Stroke 2010;41(8):1690–1696. Crossref, MedlineGoogle Scholar
  • 18 Lubicz B, Collignon L, Raphaeli G, De Witte O. Pipeline flow-diverter stent for endovascular treatment of intracranial aneurysms: preliminary experience in 20 patients with 27 aneurysms. World Neurosurg 2011;76(1-2):114–119. Crossref, MedlineGoogle Scholar
  • 19 Martin AR, Cruz JP, Matouk CC, Spears J, Marotta TR. The pipeline flow-diverting stent for exclusion of ruptured intracranial aneurysms with difficult morphologies. Neurosurgery 2012;70(1 suppl operative):21–28; discussion 28. MedlineGoogle Scholar
  • 20 Cantón G, Levy DI, Lasheras JC. Hemodynamic changes due to stent placement in bifurcating intracranial aneurysms. J Neurosurg 2005;103(1):146–155. Crossref, MedlineGoogle Scholar
  • 21 Cantón G, Levy DI, Lasheras JC, Nelson PK. Flow changes caused by the sequential placement of stents across the neck of sidewall cerebral aneurysms. J Neurosurg 2005;103(5):891–902. Crossref, MedlineGoogle Scholar
  • 22 Nelson PK, Lylyk P, Szikora I, Wetzel SG, Wanke I, Fiorella D. The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol 2011;32(1):34–40. Crossref, MedlineGoogle Scholar
  • 23 Byrne JV, Beltechi R, Yarnold JA, Birks J, Kamran M. Early experience in the treatment of intra-cranial aneurysms by endovascular flow diversion: a multicentre prospective study. PLoS ONE 2010;5(9). pii: e12492. Published September 2, 2010. Accessed September 2, 2011. Google Scholar
  • 24 Raymond J, Darsaut TE, Guilbert F, Weill A, Roy D. Flow diversion in aneurysms trial: the design of the FIAT study. Interv Neuroradiol 2011;17(2):147–153. Crossref, MedlineGoogle Scholar
  • 25 Darsaut TE, Raymond J; for the STAT Collaborative Group. The design of the STenting in Aneurysm Treatments (STAT) trial. J Neurointerv Surg. Published July 27, 2011. Accessed August 25, 2011. Google Scholar
  • 26 Mawad ME, Cekirge S, Ciceri E, Saatci I. Endovascular treatment of giant and large intracranial aneurysms by using a combination of stent placement and liquid polymer injection. J Neurosurg 2002;96(3):474–482. Crossref, MedlineGoogle Scholar
  • 27 Murayama Y, Viñuela F, Tateshima S, Viñuela F, Akiba Y. Endovascular treatment of experimental aneurysms by use of a combination of liquid embolic agents and protective devices. AJNR Am J Neuroradiol 2000;21(9):1726–1735. MedlineGoogle Scholar
  • 28 Molyneux AJ, Cekirge S, Saatci I, Gál G. Cerebral Aneurysm Multicenter European Onyx (CAMEO) trial: results of a prospective observational study in 20 European centers. AJNR Am J Neuroradiol 2004;25(1):39–51. MedlineGoogle Scholar
  • 29 Ryttlefors M, Enblad P, Kerr RS, Molyneux AJ. International subarachnoid aneurysm trial of neurosurgical clipping versus endovascular coiling: subgroup analysis of 278 elderly patients. Stroke 2008;39(10):2720–2726. Crossref, MedlineGoogle Scholar
  • 30 Brinjikji W, Rabinstein AA, Lanzino G, Kallmes DF, Cloft HJ. Effect of age on outcomes of treatment of unruptured cerebral aneurysms: a study of the National Inpatient Sample 2001-2008. Stroke 2011;42(5):1320–1324. Crossref, MedlineGoogle Scholar
  • 31 Naggara O, Raymond J, Guilbert F, Altman DG. The problem of subgroup analyses: an example from a trial on ruptured intracranial aneurysms. AJNR Am J Neuroradiol 2011;32(4):633–636. Crossref, MedlineGoogle Scholar
  • 32 Darsaut TE, Findlay JM, Raymond J; CURES collaborative group. The design of the Canadian UnRuptured Endovascular versus Surgery (CURES) trial. Can J Neurol Sci 2011;38(2):236–241. Crossref, MedlineGoogle Scholar

Article History

Received October 4, 2011; revision requested November 7; final revision received December 20; accepted January 13, 2012; final version accepted January 18.
Published online: June 2012
Published in print: June 2012