Significance of the Hemorrhagic Site for Recurrent Bleeding: Prespecified Analysis in the Japan Adult Moyamoya Trial

Background and Purpose—The primary results of the Japan Adult Moyamoya Trial revealed the statistically marginal superiority of bypass surgery over medical treatment alone in preventing rebleeding in moyamoya disease. The purpose of this analysis is to test the prespecified subgroup hypothesis that the natural course and surgical effects vary depending on the hemorrhagic site at onset. Methods—The hemorrhagic site, classified as either anterior or posterior, was the only stratifying variable for randomization. Statistical analyses were focused on the assessment of effect modification according to the hemorrhagic site and were based on tests of interaction. Results—Of 42 surgically treated patients, 24 were classified as anterior hemorrhage and 18 as posterior hemorrhage; of 38 medically treated patients, 21 were classified as anterior and 17 as posterior. The hazard ratio of the primary end points (all adverse events) for the surgical group relative to the nonsurgical group was 0.07 (95% confidence interv...