Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

Area of Science:

• Cardiology
• Nephrology
• Pharmacology

Background:

• Limited randomized data exists on apixaban's safety and efficacy for stroke prevention in atrial fibrillation (AF) patients undergoing hemodialysis.
• End-stage kidney disease (ESKD) patients on hemodialysis represent a high-risk population for thromboembolic events and bleeding complications.

Purpose of the Study:

• To compare the safety and efficacy of apixaban versus warfarin for stroke prevention in patients with AF on hemodialysis.
• To evaluate bleeding events, stroke, mortality, and apixaban pharmacokinetics in this specific patient cohort.

Main Methods:

• The prospective, randomized, open-label RENAL-AF trial enrolled 154 patients with AF on hemodialysis and a CHA 2 DS 2 -VASc score ≥ 2.
• Patients were assigned apixaban (5 mg BID, or 2.5 mg BID for specific criteria) or dose-adjusted warfarin.
• Primary outcome was time to major or clinically relevant nonmajor bleeding; secondary outcomes included stroke and mortality.

Main Results:

• The trial stopped prematurely due to enrollment challenges, resulting in inadequate power to compare bleeding rates between apixaban and warfarin.
• 1-year rates for major or clinically relevant nonmajor bleeding were 32% (apixaban) vs. 26% (warfarin); stroke/systemic embolism rates were 3.0% vs. 3.3%, respectively.
• Death was the most frequent major event; pharmacokinetic analysis showed substantial overlap in drug concentrations regardless of bleeding outcomes.

Conclusions:

• The RENAL-AF trial was underpowered to conclude on bleeding risk differences between apixaban and warfarin in AF patients with ESKD on hemodialysis.
• Clinically relevant bleeding events were significantly more frequent than strokes, underscoring the need for future studies on anticoagulation risks and benefits in this population.