ArticlesMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial
Introduction
Brain arteriovenous malformations are diagnosed most often in adults aged about 40 years. Haemorrhage was the usual means of discovery before non-invasive imaging, but in the past three decades such imaging has helped with the detection of brain arteriovenous malformations and the proportion being diagnosed unruptured has almost doubled.1, 2
An earlier retrospective series3 estimated a 4% crude annual rupture rate for brain arteriovenous malformations, but this risk was derived from combined outcomes, including those already having bled. More recent prospective studies4, 5 report bleeding rates as low as 1% per year for those discovered unruptured. Furthermore, first haemorrhage syndromes are often mild, with bleeding often mainly confined to the brain arteriovenous malformation itself or originating from the venous side of the malformation.6, 7 Approaches to eradicate a brain arteriovenous malformation, bled or not, include various treatment techniques (neurosurgery, endovascular embolisation, and stereotactic radiotherapy) used alone or in combination with varying degrees of treatment-associated morbidity and mortality.8, 9
In the past decade, debates have addressed whether preventive lesion eradication offers a clinical benefit for patients diagnosed with an unruptured brain arteriovenous malformation.10, 11 A Randomised trial of Unruptured Brain AVMs (ARUBA) was organised to address this clinically compelling question.
Section snippets
Study design and participants
ARUBA is a prospective, multicentre, parallel design, non-blinded, randomised controlled trial involving 39 active clinical sites in nine countries (appendix). Site selection was based on centre experience with management of at least ten brain arteriovenous malformations per year, presence of a multidisciplinary arteriovenous malformations treatment team, and documented academic interest in clinical brain arteriovenous malformation research.
We compare the risk of death and symptomatic stroke in
Results
We randomised 226 patients during the period from April 4, 2007, to April 15, 2013, at a mean rate of 3·2 patients per month (appendix). Figure 1 shows the trial profile. We had screened a further 1514 patients for eligibility, of whom 1014 were ineligible for enrolment, largely because of evidence of previous haemorrhage or a history of previous treatment. Of the 500 patients deemed eligible, 323 refused participation in the trial, and 42 were managed by centres that randomised no patients.
Discussion
In this study of 223 patients with unruptured brain arteriovenous malformations, the risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group after a mean follow-up of about 33 months. Patients followed up without intervention also had a significantly lower risk of death and neurological disability (modified Rankin scale ≥2) than those in the interventional group. No unexpected harms were identified, other than a higher proportion
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