OC 20.2 - Safety of factor XI inhibitors in patients with end-stage kidney disease on hemodialysis: A meta-analysis of randomized controlled trials

Background: Factor XI (FXI) has emerged as potential target for antithrombotic therapy, driven by early preclinical evidence showing a role of FXI for prevention of thrombosis without impeding hemostasis. This is particularly promising for patients at high risk of both thrombosis and bleeding, such as patients with end-stage kidney disease (ESKD) on hemodialysis, in whom the evidence for currently available anticoagulants is limited and conflicting. However, the safety of FXI inhibitors in this vulnerable patient group still needs to be established.

Aims: To assess the risk of clinically relevant bleeding (CRB, composite of major bleeding and clinically relevant non-major bleeding) and mortality in patients with ESKD on hemodialysis treated with FXI inhibitors in randomized controlled trials (RCT).

Methods: We performed a search of electronic databases (MEDLINE, Embase, CENTRAL, ClinicalTrials.gov) accompanied by a manual search for conference proceeding of identified RCTs until November 2023. RCTs comparing FXI inhibitors with any comparator in patients with ESKD on hemodialysis were considered eligible. After pooling of treatment arms, we fitted random-effects models to CRB and mortality, using odds ratios (OR) as outcome measure.

Results: We identified six RCTs assessing FXI inhibitors in patients with ESKD on hemodialysis, all using placebo as comparator. Of those, one study was still ongoing, resulting in five studies investigating FXI inhibitors (IONIS-FXIRx, xisomab, fesomersen, osocimab) encompassing 1,270 patients included in our meta-analysis (table). FXI inhibitors were associated with an OR of 0.80 (95% CI, 0.49-1.32) for the occurrence of CRB compared to placebo (Fig.). Regarding mortality, use of FXI inhibitors was associated with an OR of 0.61 (95% CI, 0.24-1.55) (Fig.).

Conclusion(s): In patients with ESKD on hemodialysis, FXI inhibitors were associated with reduced odds of CRB and death compared to placebo, although uncertainty of estimates was substantial. Future clinical trials will be needed to evaluate efficacy of FXI inhibitors in this high-risk population.