Intervention for Unruptured Brain AVMs Proves Very Harmful in the Short Term

Summary and Comment |
December 13, 2013

Intervention for Unruptured Brain AVMs Proves Very Harmful in the Short Term

  1. Hooman Kamel, MD

In a randomized trial, interventions to obliterate unruptured arteriovenous malformations led to considerably more short-term morbidity and mortality than conservative treatment.

  1. Hooman Kamel, MD

Brain arteriovenous malformations (AVMs) can rupture and cause disabling or lethal intracerebral hemorrhage. For already-ruptured AVMs, interventions such as surgical resection, radiotherapy, endovascular embolization, or a combination of these are widely accepted because of the high risk for recurrent hemorrhage. However, the advisability of intervention for unruptured AVMs is controversial. Investigators now report the results of A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), the first randomized trial of intervention versus conservative therapy for unruptured AVMs. The researchers enrolled adults with untreated AVMs that were amenable to intervention and showed no radiographic evidence of previous hemorrhage. All enrolled patients received medical management of symptoms such as headache or seizures. Half were randomly assigned to receive an intervention to obliterate the AVM, with the interventional treatment plan chosen by an experienced multidisciplinary team at each study site.

After 226 patients were enrolled, further enrollment was halted because the primary outcome of death or symptomatic stroke occurred significantly more often in the intervention arm (30.7%) than in the control arm (10.1%). Among patients with at least 30 months of follow-up, the rate of disability (modified Rankin Scale score ≥2) was significantly higher in the intervention group than in the conservative-management group (46.2% vs. 15.1%).


The subjects' baseline characteristics support the external validity of this trial; these relatively young patients with predominantly low Spetzler-Martin scores were, theoretically, ideal surgical candidates. Some will argue that benefits of arteriovenous malformation obliteration will accrue over time and outweigh the short-term harm seen here. Long-term follow-up of ARUBA participants certainly is needed to fully settle this question, but it is hard to imagine a realistic long-term benefit that could outweigh this much increased short-term risk for disability and death. Until more data become available, it seems difficult to justify routine interventional treatment of unruptured AVMs.

Editor Disclosures at Time of Publication

  • Disclosures for Hooman Kamel, MD at time of publication Consultant / Advisory board Genentech Grant / research support American Heart Association


Reader Comments (4)

Gopalakrishnan MS, MCh Physician, Surgery, Specialized, Pondicherry, India. (Jipmer)

As Bambakidis pointed out, ARUBA reveals the negative consequences of embolisation when used as the treatment for unruptured BAVMs that are ideal targets for surgical extirpatation. Since only very few patients underwent microsurgical excision, we do not have sufficient evidence to conclude that surgery is harmful (or otherwise) and hence the trial lacks external validity. However, we can definitely conclude that endovascular therapy is a bad choice. Though the trial attracted a lot of criticisms from surgeons, we must realise that grouping all interventions together was the only practical way to achieve a good sample size. Neurosurgeons were probably reluctant to randomize operable patients. That was the real problem!

Nicholas, Bambakidis, MD Physician, Surgery, Specialized, University Hospitals Case Medical Center

The reviewer of this article either did not read it carefully or is simply not educated regarding the treatment of brain AVMs. In the study, 30 patients were treated with embolization alone, which is not typically curative for these lesions (13% in a recent meta-analysis, cited in the paper). Additionally, there is no real data in the paper to confirm "obliteration" in the study group, and another 30-odd patients were treated with stereotactic radiosurgery (which takes up to 3 years to obliterate an AVM). Only 5 patients were treated with surgery, which is the gold standard of treatment (curative in up to 96% of cases). This paper is merely a comment on the high risk of embolization of AVMs (mostly in France, where the great majority of patients were randomized) as well as a confirmation of the signficant risk of observation (annual hemorrhage rate of 2.2%). NEJM Watch should monitor its reviewers better, to be sure that they actually read and understand the articles they review, rather than just summarize and parrot the conclusions, which are often flawed or open to misinterpretation.

HUSSEIN EL-HASSAN Physician, Neurology, Beirut Lebnon

I think this is still controversial. Repeated small haemorrhages is certainly an indication to intervene.

Camila Cruz

Very interesting.

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