Increase in Ruptured Cerebral Arteriovenous Malformations and Mortality in the United States: Unintended Consequences of the ARUBA Trial?

Background: The findings of the ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformation) trial, which determined that medical management was superior to prophylactic interventional therapy for the treatment of unruptured cerebral arteriovenous malformations (cAVMs), remain polarizing and controversial. Methods: Adult cAVM patient admissions were identified in the National Inpatient Sample from 2009 to 2019. The incidence of cAVM rupture and in-hospital mortality were compared between the pre- (2009-2013) and post-ARUBA trial eras (2014-2019) using complex samples-weighted estimates and multivariable logistic regression analyses. A control cohort composed of an alternate pathology (ruptured and unruptured cerebral aneurysms) was also assessed during the study period to evaluate potential bias. Results: Among 121 415 hospitalizations for cAVM during the study period, 31 389 (25.9%) were admissions for ruptured malformations. The incidence of ruptured cAVM increased in the post-ARUBA trial era (13.3% versus 34.4%; P<0.001) as well as rates of in-hospital mortality (2.0% versus 7.6%; P<0.001). Following multivariable regression analysis adjusting for age, illness severity, and acute neurological condition, the post-ARUBA trial era was independently associated with both cAVM rupture (adjusted odds ratio [OR], 1.99; [95% CI, 1.72-2.29]; P<0.001) and in-hospital mortality (adjusted OR, 1.94; [95% CI, 1.37-2.75]; P<0.001). Control cohort comparative analysis revealed that rates of hospitalizations for ruptured cerebral aneurysms relative to all aneurysm admissions did not differ before and after 2014 (84.5% versus 84.3%; P=0.185). Conclusion: The incidence of ruptured cAVM increased following 2014, potentially a reflection of a paradigm shift to conservative and noninterventional management strategies in patients with unruptured cAVM. Further studies may be necessary to exclude other confounders contributing to this rise.