Thromboembolic Events in the Hemodialysis Setting: Understanding Risk Profiles and Cumulative Incidences to Inform...

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Patients with kidney failure undergoing hemodialysis exhibit elevated risks of cardiovascular morbidity and mortality, including thromboembolic events.
• Novel Factor XIa inhibitors are under development, potentially offering antithrombotic benefits with reduced bleeding risk compared to existing therapies.

Purpose of the Study:

• To investigate major adverse vascular events (MAVEs) in a large hemodialysis cohort.
• To inform the design of future Phase 3 clinical trials for novel antithrombotic agents in this population.

Main Methods:

• Analysis of 25,211 patients on hemodialysis from the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4-7 (2009-2021).
• Definition of atherosclerotic cardiovascular disease (ASCVD) including coronary, peripheral, or cerebrovascular disease.
• Estimation of MAVE rates and cumulative incidence, stratified by ASCVD status.

Main Results:

• Over half (52%) of the cohort met ASCVD criteria.
• The MAVE composite rate (hospitalization/death) was 6.0 per 100 patient-years overall and 8.7 in the ASCVD subset.
• Three-year cumulative MAVE incidence was 13% overall and 18% in the ASCVD subset, with an estimated trial sample size of ~7000 for the ASCVD population.

Conclusions:

• Feasibility of randomized trials targeting MAVE reduction in hemodialysis patients is challenged by observed incidence, competing risks, regulatory demands, and recruitment limitations.
• These findings underscore critical considerations for developing novel therapies for systemic thromboembolic events in patients undergoing hemodialysis.