Mortality associated with arteriovenous malformation (AVM) haemorrhage is lower than expected from aneurysmal rupture or from intracerebral haemorrhage unrelated to brain AVM rupture.[42]Perret G, Nishioka H. An analysis of 545 cases of cranio-cerebral arteriovenous malformations and fistulae reported to the Cooperative Study. J Neurosurg. 1966 Oct;25(4):467-90.
http://www.ncbi.nlm.nih.gov/pubmed/5925721?tool=bestpractice.com
[91]Choi JH, Mast H, Sciacca RR, et al. Clinical outcome after first and recurrent hemorrhage in patients with untreated brain arteriovenous malformation. Stroke. 2006 May;37(5):1243-7.
http://stroke.ahajournals.org/content/37/5/1243.full
http://www.ncbi.nlm.nih.gov/pubmed/16614321?tool=bestpractice.com
Mortalities of up to 18% have been reported following AVM rupture.[1]Brown RD Jr., Wiebers DO, Torner JC, et al. Frequency of intracranial hemorrhage as a presenting symptom and subtype analysis: a population-based study of intracranial vascular malformations in Olmsted County, Minnesota. J Neurosurg. 1996 Jul;85(1):29-32.
http://www.ncbi.nlm.nih.gov/pubmed/8683279?tool=bestpractice.com
[2]Al-Shahi R, Warlow C. A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults. Brain. 2001 Oct;124(Pt 10):1900-26.
https://academic.oup.com/brain/article/124/10/1900/333474/A-systematic-review-of-the-frequency-and-prognosis
http://www.ncbi.nlm.nih.gov/pubmed/11571210?tool=bestpractice.com
Risk of haemorrhage
Given that there is no consensus regarding the risk factors for AVM rupture, let alone their relative contribution, it is extremely difficult to predict the risk of conservative management. The overall annual haemorrhage risk of 2% to 4% is used. The risk is increased during the first 5 years following haemorrhage and is highest in the first year, when rates of >30% have been reported.[34]Hernesniemi JA, Dashti R, Juvela S, et al. Natural history of brain arteriovenous malformations: a long-term follow-up study of risk of hemorrhage in 238 patients. Neurosurgery. 2008 Nov;63(5):823-9.
http://www.ncbi.nlm.nih.gov/pubmed/19005371?tool=bestpractice.com
[35]Mast H, Young WL, Koennecke HC, et al. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet. 1997 Oct 11;350(9084):1065-8.
http://www.ncbi.nlm.nih.gov/pubmed/10213548?tool=bestpractice.com
However, haemorrhage risk seems to be overestimated in patients without haemorrhagic presentation, with rates of <1% per year.[22]Stapf C, Mast H, Sciacca RR, et al. Predictors of hemorrhage in patients with untreated brain arteriovenous malformation. Neurology. 2006 May 9;66(9):1350-5.
http://www.ncbi.nlm.nih.gov/pubmed/16682666?tool=bestpractice.com
In these patients the risks of treatment may outweigh the risk of rupture.[36]Wedderburn CJ, van Beijnum J, Bhattacharya JJ, et al. Outcome after interventional or conservative management of unruptured brain arteriovenous malformation: a prospective, population-based cohort study. Lancet Neurol. 2008 Mar;7(3):223-30.
http://www.ncbi.nlm.nih.gov/pubmed/18243054?tool=bestpractice.com
One multicentre study reported a significantly lower risk of death or stroke among patients with unruptured brain AVM who were randomised to medical management than those randomised to neurosurgery, embolisation, or stereotactic radiosurgery, alone or in combination (hazard ratio 0.27, 95% confidence interval 0.14 to 0.54).[84]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 Feb 15;383(9917):614-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119885
http://www.ncbi.nlm.nih.gov/pubmed/24268105?tool=bestpractice.com
Outcome data were available for 223 patients with a mean follow-up of 33.3 months when the trial was stopped by the National Institute of Neurological Disorders and Stroke-appointed data and safety monitoring board. The composite endpoint of death or symptomatic stroke was reached in 10.1% of patients in the medical arm versus 30.7% of patients in the interventional arm.[84]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 Feb 15;383(9917):614-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119885
http://www.ncbi.nlm.nih.gov/pubmed/24268105?tool=bestpractice.com
A subsequent analysis of the 5-year follow up data showed that these differences in the composite endpoint persisted.[85]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 Jul;19(7):573-81.
http://www.ncbi.nlm.nih.gov/pubmed/32562682?tool=bestpractice.com
Proponents of the trial results argue for medical management of all unruptured AVMs. Critics point to a probable selection bias prior to randomisation, with a large number of eligible patients not enrolled, and therefore a lack of generalisability of the trial results.