Interventional Treatment vs Conservative Management of Unruptured Brain Arteriovenous Malformations.

Importance: The optimal management of unruptured brain arteriovenous malformations (AVMs) remains controversial, as the risk-benefit balance between interventional treatment and conservative management is unclear. While ARUBA (A Randomized Trial of Unruptured Brain AVMs) favored conservative management in the short term, methodologic limitations and limited follow-up have left uncertainty regarding long-term outcomes. Objective: To evaluate the association between interventional treatment and hemorrhage-free survival, compared with conservative management, in patients with unruptured AVMs. Design, Setting, and Participants: This cohort study used a target trial emulation approach based on data from the Multimodality Treatment for Brain Arteriovenous Malformation in Mainland China (MATCH) registry, a nationwide, multicenter prospective collaboration conducted from August 1, 2011, to December 31, 2021. Patients with unruptured AVMs at baseline were included. Data analyses were conducted from January 24 to April 6, 2025. Exposures: Interventional treatment (microsurgical resection, stereotactic radiosurgery, endovascular embolization, or combinations thereof) initiated within 6 months of diagnosis vs conservative management (observation and medical therapy). Main Outcomes and Measures: The primary outcome was 5-year hemorrhage-free survival, defined as survival without AVM-related hemorrhage or death. The secondary outcome was 10-year hemorrhage-free survival. Hazard ratios (HRs) and risk differences were estimated using inverse probability of censoring-weighted survival analyses following a clone-censor-weight approach. Results: Among the 1770 patients included in the analysis (median age, 26.2 [IQR, 16.5-37.6] years; 1059 [59.8%] male), the estimated 5-year hemorrhage-free survival was 96.23% (95% CI, 93.95%-97.65%) for the interventional treatment group and 89.00% (95% CI, 86.37%-91.24%) for the conservative management group, yielding a risk difference of 7.23% (95% CI, 4.78%-9.91%) and an HR for hemorrhage of 0.44 (95% CI, 0.33-0.57). At 10 years, the risk difference was 8.37% (95% CI, 2.68%-15.70%) and the HR was 0.56 (95% CI, 0.42-0.69). Subgroup analyses indicated that the benefit of the intervention was not observed in patients with high-grade AVMs or diffuse nidus, for whom outcomes were similar to those of patients with conservative management. Only microsurgical resection was consistently associated with reduced hemorrhage risk in sensitivity analyses. Conclusions and Relevance: In this nationwide cohort study using target trial emulation, interventional treatment of unruptured AVMs was associated with improved hemorrhage-free survival at 5 and 10 years. These findings support individualized decision-making in the management of unruptured AVMs and demonstrate how target trial emulation can inform clinical questions where randomized clinical trials are not feasible.