Letter: Medical Management With Interventional Therapy Versus Medical Management Alone for Unruptured Brain Arteriovenous Malformations (ARUBA): Final Follow-up of a Multicentre, Nonblinded, Randomised Controlled Trial : Neurosurgery

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Letter: Medical Management With Interventional Therapy Versus Medical Management Alone for Unruptured Brain Arteriovenous Malformations (ARUBA): Final Follow-up of a Multicentre, Nonblinded, Randomised Controlled Trial

Volovici, Victor MD, PhD; Schouten, Joost W MD; Gruber, Andreas MD, PhD; Meling, Torstein R MD, PhD; Dammers, Ruben MD, PhD

doi: 10.1093/neuros/nyaa448
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To the Editor:

Mohr and colleagues1 present the final follow-up results of the ARUBA trial (A Randomized trial of Unruptured Brain Arteriovenous malformations)1 in the latest edition of The Lancet Neurology.

ARUBA has had a profound impact on clinical practice. Nevertheless, its results have come under fierce scrutiny.2 There was a low prevalence of microsurgical resection in the intervention arm (5 patients received microsurgery alone, 13 in combination, for a total of 19%), although microsurgery is regarded as first-line therapy, especially in lower-grade lesions (Spetzler-Martin grades I and II).3 In response to this critique, the authors were “vexed” with the neurosurgical community's criticism.4 The authors’ reply seemed more akin to an ignoratio elenchi. It would be disingenuous to suggest that, because there are apparent disparities between the American neurosurgical community and trial coordinators, leading to under-representation of microsurgery in the intervention arm, the conclusions of the trial apply, nevertheless, to microsurgery.

The key to interpreting ARUBA lies in its methodology. Complex surgical interventions tested in a randomized control trial pose considerable problems on their own and usually require very large sample sizes in order to test a fairly well standardized procedure. Instead, ARUBA chose to mirror real-world practice and was designed as a “hybrid,” part explanatory, part pragmatic,5 trial. It amalgamates all 3 treatment modalities and their combinations into a “black box,” which leads to a highly heterogeneous definition of the intervention being studied. ARUBA, therefore, puts decision-making in brain arteriovenous malformations (bAVMs) on trial, and not any individual treatment modality or their combinations.

The included study population comprised >50% low-grade unruptured bAVMs The prevalence of hemorrhagic stroke alone in the intervention arm of ARUBA is alarmingly high,1 even compared to the pooled results of treatments for both ruptured and unruptured bAVMs.2 We therefore wholeheartedly support the authors’ conclusions that treating patients with unruptured bAVMs as mirrored by the intervention arm of the trial should be avoided at all costs.

As with any scientific debate, the truth lies in the nuance and not in veracious extremes, which either discredit ARUBA as being completely flawed or use it as evidence that no unruptured bAVM should ever be treated by any modality. Both conclusions are the result of unflattering logic. Microsurgery remains a valid treatment option, especially for low-grade bAVMs, but the evidence base is low and should be improved.

With poor decision-making out of the way, we owe it to our patients to step away from emotionally driven arguments and work together to determine the proper timing and treatment modality for these lesions. The final results of ARUBA merely provide grounds for further research and give microsurgery the chance (and the responsibility) to strengthen its evidence base.

Funding

This study did not receive any funding or financial support.

Disclosures

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

REFERENCES

1. Mohr   JP, Overbey   JR, Hartmann   A, et al.  Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial. Lancet Neurol. 2020;19(7):573-581.
2. Meling   TR, Proust   F, Gruber   A, et al.  On apples, oranges, and ARUBA. Acta Neurochir. 2014;156(9):1775-1779.
3. Wong   J, Slomovic   A, Ibrahim   G, Radovanovic   I, Tymianski   M. Microsurgery for ARUBA trial (A Randomized trial of Unruptured Brain Arteriovenous malformation)-eligible unruptured brain arteriovenous malformations. Stroke. 2017;48(1):136-144.
4. Stapf   C, Parides   MK, Moskowitz   AJ, Mohr   JP. Management of brain arteriovenous malformations—authors' reply. Lancet. 2014;383(9929):1635-1636.
5. Kent   DM, Kitsios   G.  Against pragmatism: on efficacy, effectiveness and the real world. Trials. 2009;10:48.
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