Ruptured Cerebral Arteriovenous Malformations Rate Has Increased Since ARUBA Trial

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A study was conducted to determine incidence of hospitalizations for cAVM rupture before and after the ARUBA trial.

The incidence of ruptured cerebral arteriovenous malformations (cAVMs) and related in-hospital mortality has increased significantly since 2014, according to a study published in Stroke: Vascular and Interventional Neurology.

Investigators aimed to evaluate the incidence of hospitalizations associated with cAVM rupture before and after the ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformation; Identifier: NCT00389181) trial to determine the potential consequences of a paradigm shift toward conservative unruptured cAVM management starting in 2014.

Adult patients (aged >17 years) with admission diagnoses of cAVM with and without associated rupture from 2009 to 2019 were identified from the National Inpatient Sample (NIS) based on International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9/10-CM) codes.

The researchers measured and compared variation in baseline demographic and clinical characteristics before (2009-2013) and after (2014-2019) the publication of the ARUBA findings in patients with unruptured cAVM and those with ruptured cAVM.

A control group of patients with cerebral aneurysms, for which clinical management was not affected by the ARUBA trial results, was included to assess the potential for bias. The primary clinical endpoints were ruptured cAVM and in-hospital mortality.

Of 121,415 hospitalizations (mean age [SEM], 53.7 [0.2] years; 50.4% women) for cAVM from 2009 to 2019, 31,389 (25.9%) were admissions for ruptured malformations. Among the total cohort, 49,345 participants (40.6%; mean age, 51.4 [0.1] years; 50.9% women) were in the pre-ARUBA era and 72,070 (59.4%; mean age, 55.3 [0.1] years; 50% women) were in the post-ARUBA era.

The ruptured cAVM incidence increased significantly after the ARUBA trial was published (13.3% vs 34.4%; P <.001), as did the rates of in-hospital mortality (2.0% vs 7.6%; P <.001).

The period after the ARUBA trial was independently associated with cAVM rupture (adjusted odds ratio [aOR], 1.99; 95% CI, 1.72-2.29; P <.001) and in-hospital mortality (aOR, 1.94; 95% CI, 1.37-2.75; P <.001), after multivariable logistic regression analysis that adjusted for age, illness severity, and acute neurologic condition.

Among the control group (n=1,108,645), the hospitalization rate for ruptured aneurysms relative to unruptured aneurysms did not differ significantly before (n=457,980) and after 2014 (n=477,915) (84.5% vs 84.3%; P =.185). The mortality rates in this group decreased significantly after 2014 (20.0% vs 18.4%; P <.001).

The investigators note that they are unable to establish causation because the data do not include the granularity necessary to eliminate potential confounders, such as differences in imaging modalities or frequency of diagnosing cAVMs in elderly individuals. Also, the clinical parameters are based on ICD billing codes, which lack disease-specific covariates and may contribute to heterogeneity in identification of patients.

“The incidence of ruptured cAVM and associated mortality is rising in the United States, which may be attributed to a paradigm shift toward conservative and noninterventional management strategies in patients with unruptured cAVM,” wrote the study authors. “Further studies may be needed to exclude other confounders for these findings.”


Dicpinigaitis AJ, Ogulnick JV, Mayer SA, Gandhi CD, Al-Mufti F. Increase in ruptured cerebral arteriovenous malformations and mortality in the United States: unintended consequences of the ARUBA trial? Stroke Vasc Interv Neurol. Published online July 14, 2022. doi: 10.1161/SVIN.122.000442