Editorial: The ARUBA study: where do we go from here?

Abstract

T he highly controversial ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malfor-mations) study marked an important turning point in the history of the management of unruptured cerebral arteriovenous malformations (AVMs). 4 This issue of the Journal of Neurosurgery includes a very thoughtful and important paper by Magro and colleagues, addressing the various critiques that have been published since the in-ception of the study in 2006. 3 However, before discussing the current paper, we would like to briefly summarize the design and results of the ARUBA trial. The ARUBA study was the first prospective multi-center randomized controlled trial (RCT) comparing medical management alone to medical management and prophylactic interventional therapy (endovascular, surgi-cal, and radiation therapy, alone or in combination) in pa-tients with unruptured AVMs. The primary end point was the composite measure of death from any cause or any stroke, which was defined as any symptom associated with any imaging finding. The secondary analysis was overall functional status and quality of life at a minimum of 5 years from randomization. An interim analysis performed after 6 years led to discontinuation of the study due to ex-cessive morbidity in the treatment arm as compared with the conservatively treated cohort. A total of 223 patients had been enrolled in the trial, with a mean follow-up of ap-proximately 33.3 months. The primary outcome was seen in 11 (10.1%) of the 109 patients assigned to the medical group and in 35 patients (30.7%) of the 114 patients as-signed to the intervention group. Even prior to commencement of enrollment, the design of the ARUBA study had been heavily criticized, particu-larly in regard to the proposed 5-year follow-up period, which many argued would unfairly detect all procedure-related complications but would be too short to detect the potential long-term benefits of prophylactic intervention. It was therefore not a surprise to most when the study was prematurely interrupted and the results were in favor of conservative therapy. Numerous editorials and commen-taries discussing the weaknesses of the trial soon fol-lowed. 1 However, despite the widely discussed limitations, many have interpreted the results as indicative that no un-ruptured AVM should be treated at all. 2