Factor Xa inhibitor associated major bleeding characteristics, burden, and health resource utilization in Alberta, Canada - an observational population based study

Background Bleeding events remain the most significant complication associated with oral and parenteral anticoagulation and have related morbidity and mortality. The objectives were to determine the incidence and risk factors for major bleeding and associated adverse clinical outcomes and health care resource utilization during new Factor Xa inhibitor (FXaI) treatment stratified by indication and bleeding location. Methods Patients aged 18-89 with a new FXaI prescription between 2008 and 2018, without previous anticoagulation or major bleeding in the 60 days prior, were selected. Administrative data obtained from pharmacy, laboratory, physician and hospitalization databases were used for baseline characteristics and bleeding event identification. Results 75,806 patients were identified. Major bleeding incidence during new FXaI use was 11.5 per 100-person-years (100 PYR). Parenteral FXaI had the highest overall rates of 29.7 per 100 PYR at three years and 35.2 per 100 PYR within the first three months while those on DOAC therapy had an overall bleeding incidence rate of 9.1 per 100 PYR at three years and 15.8 per 100 PYR in the first three months. Patients with atrial fibrillation (10.4 per 100 PYR) had the lowest, and patients postcardiac valve replacement (25.7 per 100 PYR) had the highest incidence rate of major bleeding. Intracerebral hemorrhage (ICH) was the most infrequent bleed location (6.1%) but was fatal in 34% and in index survivors 54% suffered all cause mortality by 3 years; with all cause mortality by bleeding type shown in figure. Total costs in year one for major bleed events (n=5,332) were $253.5 million (2022 $CAD), of which $132.1 million were temporally associated with major bleed events (figure Cost per bleeding type). Conclusion The incidence of major bleeding was 11.5 per 100 PYR, ICH comprising the lowest rate of major bleeding type but highest mortality. The health care cost burden of major bleeding events is substantial and warrants further investigation.