Chronic kidney disease is present in almost 10% of the world population and is associated with excess mortality and morbidity. Reduced glomerular filtration rate and the presence and extent of
proteinuria, key domains of
chronic kidney disease, have both been shown to be strong and independent risk factors for cardiovascular disease. Patients with
kidney failure requiring dialysis are at highest risk for cardiovascular events (e.g.,
stroke or
myocardial infarction), and of developing chronic cardiovascular conditions, such as
heart failure. Despite the high burden of
cardiovascular disease, there is a paucity of evidence supporting
therapies to reduce this risk. Although long-term
anticoagulant treatment has the potential to prevent
thromboembolism in persons with
kidney failure on dialysis, this possibility remains understudied. The limited data available on anticoagulation in patients with
kidney failure has focused on
vitamin K antagonists or direct oral
anticoagulants that inhibit
thrombin or factor (F) Xa. The risk of
bleeding is a major concern with these agents. However, FXI is emerging as a potential safer target for new
anticoagulants because FXI plays a greater part in
thrombosis than in hemostasis. In this article, we (i) explain the rationale for considering anticoagulation
therapy in patients with
kidney failure to reduce atherothrombotic events, (ii) highlight the limitations of current
anticoagulants in this patient population, (iii) explain the potential benefits of FXI inhibitors, and (iv) summarize ongoing studies investigating FXI inhibition in patients with
kidney failure on dialysis.