Cardiovascular events in aging Japanese people with hemophilia: a 3-year interim analysis of the ADVANCE Japan cohort

As life expectancy increases in people with hemophilia (PWH), cardiovascular disease (CVD) has emerged as an important comorbidity. However, prospective data on CVD occurrence and its clinical management remain limited. We performed a prespecified 3-year interim analysis of ADVANCE Japan, an ongoing 10-year multicenter prospective cohort study of PWH aged ≥ 40 years, to describe CVD occurrence, clinical management, bleeding outcomes, and associated changes in hemostatic treatment. We also explored factors associated with CVD occurrence using Cox proportional hazards models. Among 588 participants, 24 developed CVD, yielding 26 events over 3 years (cumulative incidence, 4.1%). Ischemic heart disease was the most frequent event. Exploratory analyses suggested that older age, dyslipidemia, and current smoking were associated with CVD occurrence, although estimates were imprecise because of the limited number of events. Antiplatelet or anticoagulant therapy was administered to selected patients, and hemostatic management was frequently modified following CVD events. One major bleeding event was observed among patients receiving antithrombotic therapy. This prespecified interim analysis provides prospective real-world data on the occurrence and clinical management of CVD in aging Japanese PWH. Risk factor analyses should be considered exploratory, and continued follow-up is required to define long-term cardiovascular risk and outcomes in this population.