Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: A national sample analysis



      The real-world evolution of management and outcomes of patients with unruptured brain arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs. initial conservative medical therapy.


      We analyzed the National Inpatient Sample from 2009-2018, capturing 20% of all admissions in the U.S. Validated ICD-9 and -10 codes defined brain AVMs, comorbidities, and the use of interventional modalities. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018).


      Among the national projected 88,037 AVM admissions, 72,812 (82.7%) were unruptured AVMs and 15,225 (17.3%) were ruptured AVMs. Among uAVMs, 51.4% admitted pre-ARUBA and 48.6% in post-ARUBA period. The post-ARUBA patients were mildly older (median age 53.3 vs. 51.8 (p = 0.001) and had more comorbidities including hypertension, diabetes, obesity, renal impairment, and smoking. Before the first platform report of ARUBA (2009-2012), rates of use of interventional treatments during uAVM admissions trended up from 31.8% to 35.4%. Thereafter, they declined significantly to 26.4% in 2018 (p = 0.02). The decline was driven by a reduction in the frequency of endovascular treatment from 18.8% to 13.9% and inpatient stereotactic radiosurgery from 0.5% to 0.1%. No change occurred in the frequency of microsurgery or combined endovascular and surgical approaches. Adjusted multivariable model of uAVMs showed increased odds of discharge to a long-term inpatient facility or in-hospital death [OR 1.14 (1.02-1.28), p = 0.020] in post-ARUBA. A significantly increased proportion of ruptured AVMs from 17.0% to 23.3% was observed consistently in post-ARUBA.


      Nationwide practice in the management of unruptured AVMs changed substantially with the publication of the ARUBA trial in a durable and increasing manner. Fewer admissions with the interventional treatment of unruptured AVMs occurred, and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event. Further studies are needed to determine whether these trends can be considered to be ARUBA trial effect or are merely coincidental.


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        • Solomon RA
        • Connolly ES.
        Arteriovenous malformations of the brain.
        N Engl J Med. 2017; 376: 1859-1866
        • Stapf C
        • Mohr JP.
        Unruptured brain arteriovenous malformations should be treated conservatively.
        Stroke. 2007; 38: 3308-3309
        • Cockroft KM.
        Unruptured brain arteriovenous malformations should be treated conservatively.
        Stroke. 2007; 38: 3310-3311
        • Mohr JP
        • Parides MK
        • Stapf C
        • et al.
        Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.
        Lancet. 2014; 383: 614-621
        • 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: 573-581
        • Magro E
        • Gentric JC
        • Darsaut TE
        • et al.
        Responses to ARUBA: a systematic review and critical analysis for the design of future arteriovenous malformation trials.
        J Neurosurg. 2017; 126: 486-494
        • Link TW
        • Winston G
        • Schwarz JT
        • et al.
        Treatment of unruptured brain arteriovenous malformations: a single-center experience of 86 patients and a critique of the a randomized trial of unruptured brain arteriovenous malformations (ARUBA) trial.
        World Neurosurg. 2018; 120: e1156-e1162
        • Birnbaum LA
        • Straight M
        • Hegde S
        • et al.
        Microsurgery for unruptured cerebral arteriovenous malformations in the national inpatient sample is more common Post-ARUBA.
        World Neurosurg. 2020; 137: e343-e346
        • Wahood W
        • Alexander AY
        • Doherty RJ
        • et al.
        Elective intervention for unruptured cranial arteriovenous malformations in relation to ARUBA trial: a National Inpatient Sample study.
        Acta Neurochir. 2021; 163: 2489-2495
        • Reynolds AS
        • Chen ML
        • Merkler AE
        • et al.
        Effect of a randomized trial of unruptured brain arteriovenous malformation on interventional treatment rates for unruptured arteriovenous malformations.
        Cerebrovasc Dis. 2019; 47: 299-302
        • HCUP Home
        Healthcare Cost and Utilization Project (HCUP).
        Agency for Healthcare Research and Quality, Rockville, MD2020
        • HCUP Databases
        Healthcare Cost and Utilization Project (HCUP).
        Agency for Healthcare Research and Quality, Rockville, MD2019
        • Kim HJ
        • Fay MP
        • Feuer EJ
        • Midthune DN.
        Permutation tests for joinpoint regression with applications to cancer rates.
        Stat Med. 2000; 19: 335-351
        • Derdeyn CP
        • Zipfel GJ
        • Albuquerque FC
        • et al.
        Management of brain arteriovenous malformations: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association.
        Stroke. 2017; 48: e200-e224
        • Green LW
        • Ottoson JM
        • García C
        • Hiatt RA.
        Diffusion theory and knowledge dissemination, utilization, and integration in public health.
        Ann Rev Public Health. 2009; 30: 151-174
        • Balas EA
        • Boren SA.
        Managing Clinical Knowledge for Health Care Improvement.
        • Grant J
        • Green L
        • Mason B.
        Basic research and health: a reassessment of the scientific basis for the support of biomedical science.
        Res Eval. 2003; 12: 217-224
        • Al-Shahi Salman R
        • White PM
        • Counsell CE
        • et al.
        Outcome after conservative management or intervention for unruptured brain arteriovenous malformations.
        JAMA. 2014; 311: 1661-1669