The Rationale Behind “A Randomized Trial of Unruptured Brain AVMs” (ARUBA)

Objective:To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA).Methods:We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ≥2. ARUBA closed recruitment on April 15, 2013.Results:After a median of 33.3 months of follow-up (interquartile range 16.3–49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ≥2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11–0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04–0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT (p < 0.001).Conclusion:Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades.ClinicalTrials.gov identifier:NCT00389181.Classification of evidence:This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ≈3 years.

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Effect of A Randomized trial of Unruptured Brain Arteriovenous Malformation on Interventional Treatment Rates for Unruptured Arteriovenous Malformations

Cerebrovascular Diseases ◽

10.1159/000502314 ◽

2019 ◽

Vol 47 (5-6) ◽

pp. 299-302 ◽

Cited By ~ 5

Author(s):

Alexandra S. Reynolds ◽

Monica L. Chen ◽

Alexander E. Merkler ◽

Abhinaba Chatterjee ◽

Iván Díaz ◽

...

Keyword(s):

Randomized Trial ◽

Arteriovenous Malformations ◽

Population Level ◽

International Classification Of Diseases ◽

Interventional Treatment ◽

Classification Of Diseases ◽

Nationally Representative ◽

Brain Avms ◽

Join Point ◽

Procedure Codes

Background: In 2013, investigators from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (AVM; ARUBA) reported that interventions to obliterate unruptured AVMs caused more morbidity and mortality than medical management. Objective: We sought to determine whether interventions for unruptured AVM decreased after publication of ARUBA results. Methods: We used the Nationwide Readmissions Database to assess trends in interventional AVM management in patients ≥18 years of age from 2010 through 2015. Unruptured brain AVMs were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 747.81 and excluding any patient with a diagnosis of intracranial hemorrhage. Our primary outcome was interventional AVM treatment, identified using ICD-9-CM procedure codes for surgical resection, endovascular therapy, and stereotactic radiosurgery. Join-point regression was used to assess trends in the incidence of interventional AVM management among adults from 2010 through 2015. Results: There was no significant U.S. population level change in unruptured brain AVM intervention rates before versus after ARUBA (p = 0.59), with the incidence of AVM intervention ranging from 8.0 to 9.2 per 10 million U.S. residents before the trial publication to 7.7–8.3 per 10 million afterwards. Conclusions: In a nationally representative sample, we found no change in rates of interventional unruptured AVM management after publication of the ARUBA trial results.

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Abstract 52: Clinical Impairment in Patients Followed With or Without Interventional Therapy in a Randomized Trial of Unruptured Brain Avms (aruba)

Stroke ◽

10.1161/str.47.suppl_1.52 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

JP Mohr ◽

J R Overbey ◽

Christian Stapf ◽

Andreas Hartmann ◽

Marco Antonio Stefani ◽

...

Keyword(s):

Treatment Group ◽

Randomized Trial ◽

Functional Impairment ◽

Medical Management ◽

Primary Outcome ◽

Interventional Therapy ◽

Martin Grade ◽

Brain Avms ◽

Outcome Event

Background and Purpose: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) compared outcome after interventional treatment of unbled brain AVMs with medical management. Follow-up data to assess pre-specified functional impairment after primary outcome events by treatment group and exploratory analyses by Spetzler-Martin grade are presented. Methods: We examined functional impairment using the modified Rankin scale score (mRS ≥2) at the time of primary outcome (death or stroke) by treatment group, and an exploratory analysis with these outcomes by Spetzler-Martin Grade. Analyses were performed both by intention to treat (as randomized) and as treated. Results: After a median of 42 months of follow-up, the median post-primary outcome event mRS for those ‘ as randomized ’ to medical management (MM) was 2 (IQR: 1,4) versus 3 (IQR: 1,5) in the interventional therapy (IT) arm. Values for those ‘ as treated’ , were 1 (IQR: 1,5) versus 4 (IQR: 2,5). The risk of functional impairment, as measured by an mRS ≥2 after a primary outcome event, was significantly lower for patients ‘ as randomized’ to MM (8/110, 7%) compared to IT (27/116, 23%) (HR 0.26, 95%CI 0.12, 0.57), and even lower for those ‘as treated’ (4/122, 3% vs 31/104, 30%; HR 0.09, 95% CI 0.03,0.27). Spetzler-Martin Grade and primary outcome events were not associated in the medical arm (p=0.80) but were so with increasing grades in the interventional arm (p=0.0002). Conclusion: In ARUBA, a death or stroke with a significant increase in functional impairment was more common for patients undergoing preventive intervention compared to those randomized to medical management.

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