Functional impairments for outcomes in a randomized trial of unruptured brain AVMs

J. P. Mohr; Jessica R. Overbey; Ruediger Von Kummer; Marco A. Stefani; Richard Libman; Christian Stapf; Michael K. Parides; John Pile-Spellman; Ellen Moquete; Claudia S. Moy; Eric Vicaut; Alan J. Moskowitz; Kirsty Harkness; Charlotte Cordonnier; Alessandra Biondi; Emmanuel Houdart; Joachim Berkefeld; Catharina J.M. Klijn; Xavier Barreau; Helen Kim; Andreas Hartmann

doi:10.1212/WNL.0000000000004532

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs

J. P. Mohr, Jessica R. Overbey, Ruediger Von Kummer, Marco A. Stefani, Richard Libman, Christian Stapf, Michael K. Parides, John Pile-Spellman, Ellen Moquete, Claudia S. Moy, Eric Vicaut, Alan J. Moskowitz, Kirsty Harkness, Charlotte Cordonnier, Alessandra Biondi, Emmanuel Houdart, Joachim Berkefeld, Catharina J.M. Klijn, Xavier Barreau, Helen KimAndreas Hartmann

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1499-1506
Number of pages	8
Journal	Neurology
Volume	89
Issue number	14
DOIs	https://doi.org/10.1212/WNL.0000000000004532
State	Published - Oct 3 2017
Externally published	Yes

ASJC Scopus subject areas

Clinical Neurology

Access to Document

10.1212/WNL.0000000000004532

Cite this

Mohr, J. P., Overbey, J. R., Von Kummer, R., Stefani, M. A., Libman, R., Stapf, C., Parides, M. K., Pile-Spellman, J., Moquete, E., Moy, C. S., Vicaut, E., Moskowitz, A. J., Harkness, K., Cordonnier, C., Biondi, A., Houdart, E., Berkefeld, J., Klijn, C. J. M., Barreau, X., ... Hartmann, A. (2017). Functional impairments for outcomes in a randomized trial of unruptured brain AVMs. Neurology, 89(14), 1499-1506. https://doi.org/10.1212/WNL.0000000000004532

Mohr, JP, Overbey, JR, Von Kummer, R, Stefani, MA, Libman, R, Stapf, C, Parides, MK, Pile-Spellman, J, Moquete, E, Moy, CS, Vicaut, E, Moskowitz, AJ, Harkness, K, Cordonnier, C, Biondi, A, Houdart, E, Berkefeld, J, Klijn, CJM, Barreau, X, Kim, H & Hartmann, A 2017, 'Functional impairments for outcomes in a randomized trial of unruptured brain AVMs', Neurology, vol. 89, no. 14, pp. 1499-1506. https://doi.org/10.1212/WNL.0000000000004532

@article{13dda8a5c4e24f468b0b3597e52599a6,

title = "Functional impairments for outcomes in a randomized trial of unruptured brain AVMs",

abstract = "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.",

author = "Mohr, {J. P.} and Overbey, {Jessica R.} and {Von Kummer}, Ruediger and Stefani, {Marco A.} and Richard Libman and Christian Stapf and Parides, {Michael K.} and John Pile-Spellman and Ellen Moquete and Moy, {Claudia S.} and Eric Vicaut and Moskowitz, {Alan J.} and Kirsty Harkness and Charlotte Cordonnier and Alessandra Biondi and Emmanuel Houdart and Joachim Berkefeld and Klijn, {Catharina J.M.} and Xavier Barreau and Helen Kim and Andreas Hartmann",

note = "Funding Information: J. Mohr: NINDS ARUBA grant funding U01 NS051483. No other personal funding apart from reimbursement for attending meetings and honoraria for grand rounds presentations 2015 at Beth Israel New York City, University of Miami, University of Arizona (Tucson), and Houston TX; for 2016, only reimbursement for attending meetings. Donations made to Columbia Development Office in 2015 and 2016 from the Vital Projects Fund and Richard and Jenny Levine Foundation assisted in funding follow-up data after the discontinuation of NINDS funding in August 2013. J. Overbey: NINDS ARUBA grant UO1 NS51566 salary support as study statistician. R. von Kummer: salaried chief of university interventional neuroradiology in Dresden Germany; institution reimbursed from the grant for case enrollment. M. Stefani: salaried chief of university interventional neuroradiology Federal University of Rio Grande do Sul, Porto Alegre, Brazil; reimbursed by the grant for case enrollment from his center. R. Libman: salaried vice-chairman of Neurology, Long Island Jewish Hospital, New Hyde Park, NY, reimbursed from the grant for case enrollment. C. Stapf: NINDS ARUBA grant UO1 NS51566, coprincipal investigator. M. Parides: NINDS ARUBA grant UO1 NS51566, principal statistician for the Statistical Coordinating Center. J. Pile-Spellman: voluntary staff interventional neuroradiologist at Winthrop University Hospital, Mineola, NY, and partner at Neurologic Surgery PC. He was reimbursed by the grant for case enrollment. E. Moquete: NINDS ARUBA grant UO1 NS51566; study leader for coordination of data submission from the 39 sites in the trial. C. Moy: NINDS project scientist. E. Vicaut: ARUBA reimbursement for patient enrollment at Lariboisi{\`e}re, Paris. A. Moskowitz: NINDS ARUBA grant UO1 NS51566 UO1 NS51566, principal investigator of the Statistical Coordinating Center. K. Harkness: salaried neurologist in Sheffield UK, reimbursed from the grant for case enrollment. C. Cordonnier: salaried chief of university Neurology in Lille France, reimbursed from the grant for case enrollment. A. Biondi: salaried chief of university interventional neuroradiology in Besan{\c c}on, France, reimbursed from the grant for case enrollment. E. Houdart: salary as interventional radiologist at Lariboi-si{\`e}re, Paris, and interventional neuroradiologists at the European Coordinating Center, reimbursed from the grant for case enrollment. J. Berkefeld: salaried chief of university interventional neuroradiology in Frankfurt Germany, reimbursed from the grant for case enrollment. C. Klijn, MD: Neurologist at the University Medical Center Utrecht, the Netherlands (after ARUBA relocated to Nijmegen), reimbursed from the grant for case enrollment. X. Barreau: salaried chief of university interventional neuroradiology in Bordeaux France, reimbursed from the grant for case enrollment. H. Kim; NINDS-funded investigator from other grants, reimbursed from the grant for case enrollment at her center at University of California at San Francisco. A. Hartmann: salary as chair of Neurology Frankfurt-Oder and recipient of grant funds for reimbursement for patient enrollment. Go to Neurology.org for full disclosures. Funding Information: Funded internationally by the US NIH/NINDS via cooperative agreements U01NS051483 (Clinical Coordinating Center; J.P. Mohr, principal investigator) and U01 NS051566 (Data Coordinating Center; A.J. Moskowitz, principal investigator). Gift support was also provided after cessation of NINDS funding from the Richard & Jenny Levine Foundation and the Vital Projects Fund. Publisher Copyright: {\textcopyright} 2017 American Academy of Neurology.",

year = "2017",

month = oct,

day = "3",

doi = "10.1212/WNL.0000000000004532",

language = "English (US)",

volume = "89",

pages = "1499--1506",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "14",

}

TY - JOUR

T1 - Functional impairments for outcomes in a randomized trial of unruptured brain AVMs

AU - Mohr, J. P.

AU - Overbey, Jessica R.

AU - Von Kummer, Ruediger

AU - Stefani, Marco A.

AU - Libman, Richard

AU - Stapf, Christian

AU - Parides, Michael K.

AU - Pile-Spellman, John

AU - Moquete, Ellen

AU - Moy, Claudia S.

AU - Vicaut, Eric

AU - Moskowitz, Alan J.

AU - Harkness, Kirsty

AU - Cordonnier, Charlotte

AU - Biondi, Alessandra

AU - Houdart, Emmanuel

AU - Berkefeld, Joachim

AU - Klijn, Catharina J.M.

AU - Barreau, Xavier

AU - Kim, Helen

AU - Hartmann, Andreas

N1 - Funding Information: J. Mohr: NINDS ARUBA grant funding U01 NS051483. No other personal funding apart from reimbursement for attending meetings and honoraria for grand rounds presentations 2015 at Beth Israel New York City, University of Miami, University of Arizona (Tucson), and Houston TX; for 2016, only reimbursement for attending meetings. Donations made to Columbia Development Office in 2015 and 2016 from the Vital Projects Fund and Richard and Jenny Levine Foundation assisted in funding follow-up data after the discontinuation of NINDS funding in August 2013. J. Overbey: NINDS ARUBA grant UO1 NS51566 salary support as study statistician. R. von Kummer: salaried chief of university interventional neuroradiology in Dresden Germany; institution reimbursed from the grant for case enrollment. M. Stefani: salaried chief of university interventional neuroradiology Federal University of Rio Grande do Sul, Porto Alegre, Brazil; reimbursed by the grant for case enrollment from his center. R. Libman: salaried vice-chairman of Neurology, Long Island Jewish Hospital, New Hyde Park, NY, reimbursed from the grant for case enrollment. C. Stapf: NINDS ARUBA grant UO1 NS51566, coprincipal investigator. M. Parides: NINDS ARUBA grant UO1 NS51566, principal statistician for the Statistical Coordinating Center. J. Pile-Spellman: voluntary staff interventional neuroradiologist at Winthrop University Hospital, Mineola, NY, and partner at Neurologic Surgery PC. He was reimbursed by the grant for case enrollment. E. Moquete: NINDS ARUBA grant UO1 NS51566; study leader for coordination of data submission from the 39 sites in the trial. C. Moy: NINDS project scientist. E. Vicaut: ARUBA reimbursement for patient enrollment at Lariboisière, Paris. A. Moskowitz: NINDS ARUBA grant UO1 NS51566 UO1 NS51566, principal investigator of the Statistical Coordinating Center. K. Harkness: salaried neurologist in Sheffield UK, reimbursed from the grant for case enrollment. C. Cordonnier: salaried chief of university Neurology in Lille France, reimbursed from the grant for case enrollment. A. Biondi: salaried chief of university interventional neuroradiology in Besançon, France, reimbursed from the grant for case enrollment. E. Houdart: salary as interventional radiologist at Lariboi-sière, Paris, and interventional neuroradiologists at the European Coordinating Center, reimbursed from the grant for case enrollment. J. Berkefeld: salaried chief of university interventional neuroradiology in Frankfurt Germany, reimbursed from the grant for case enrollment. C. Klijn, MD: Neurologist at the University Medical Center Utrecht, the Netherlands (after ARUBA relocated to Nijmegen), reimbursed from the grant for case enrollment. X. Barreau: salaried chief of university interventional neuroradiology in Bordeaux France, reimbursed from the grant for case enrollment. H. Kim; NINDS-funded investigator from other grants, reimbursed from the grant for case enrollment at her center at University of California at San Francisco. A. Hartmann: salary as chair of Neurology Frankfurt-Oder and recipient of grant funds for reimbursement for patient enrollment. Go to Neurology.org for full disclosures. Funding Information: Funded internationally by the US NIH/NINDS via cooperative agreements U01NS051483 (Clinical Coordinating Center; J.P. Mohr, principal investigator) and U01 NS051566 (Data Coordinating Center; A.J. Moskowitz, principal investigator). Gift support was also provided after cessation of NINDS funding from the Richard & Jenny Levine Foundation and the Vital Projects Fund. Publisher Copyright: © 2017 American Academy of Neurology.

PY - 2017/10/3

Y1 - 2017/10/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85030763317&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030763317&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000004532

DO - 10.1212/WNL.0000000000004532

M3 - Article

C2 - 28878048

AN - SCOPUS:85030763317

SN - 0028-3878

VL - 89

SP - 1499

EP - 1506

JO - Neurology

JF - Neurology

IS - 14

ER -

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this