Natural history of cerebral arteriovenous malformations: a meta-analysis

Object. The purpose of this report was to provide overall arteriovenous malformation (AVM) hemorrhage rates and, with enhanced statistical power, to elucidate significant risk factors for hemorrhage. Methods. The authors performed a meta-analysis via the PubMed database through January 2012 using the terms AVM, arteriovenous malformation, natural history, bleed, and hemorrhage. Additional studies were identified through reference searches in each reviewed article. English language studies providing annual hemorrhage rates for AVMs were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hazard ratios for hemorrhage risk factors. The analysis was performed using a random effects model. Results. Nine natural history studies with 3923 patients and 18,423 patient-years of follow-up were identified for analysis. The overall annual hemorrhage rate was 3.0% (95% CI 2.7%-3.4%). The rate of hemorrhage was 2.2% (95% CI 1.7%-2.7%) for unruptured AVMs and 4.5% (95% CI 3.7%-5.5%) for ruptured AVMs. Prior hemorrhage (HR 3.2, 95% CI 2.1-4.3), deep AVM location (HR 2.4, 95% CI 1.4-3.4), exclusively deep venous drainage (HR 2.4, 95% CI 1.1-3.8), and associated aneurysms (HR 1.8, 95% CI 1.6-2.0) were statistically significant risk factors for hemorrhage. Any deep venous drainage (HR 1.3, 95% CI 0.9-1.75) and female sex (HR 1.4, 95% CI 0.6-2.1) demonstrated a trend toward an increased risk of hemorrhage that was not statistically significant. Small AVM size and older patient age were not significant risk factors for hemorrhage. Conclusions. Arteriovenous malformations with prior hemorrhage, deep location, exclusively deep venous drainage, and associated aneurysms have greater annual hemorrhage rates than their counterparts, influencing surgical decision making and the selection of radiosurgery for these lesions.