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

Background: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF).

Methods: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHADS-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.

Apixaban Pharmacokinetics and Pharmacodynamics in Subjects with Mild or Moderate Hepatic Impairment.

Background: Hepatic impairment can impact apixaban pharmacokinetics and pharmacodynamics by decreasing cytochrome P450-mediated metabolism and factor X production.

Objective: This study evaluated the effect of mild or moderate (Child-Pugh A and B) hepatic impairment on apixaban pharmacokinetics, pharmacodynamics, and safety.

Methods: This open-label, parallel-group, single-dose study included eight mildly and eight moderately hepatically impaired subjects, and 16 healthy subjects.

Apixaban Single-Dose Pharmacokinetics, Bioavailability, Renal Clearance, and Pharmacodynamics Following Intravenous and Oral Administration.

This randomized, double-blind, placebo-controlled, ascending single intravenous (IV) bolus-dose study evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of apixaban, a direct factor Xa (FXa) inhibitor approved for multiple indications. Eight healthy subjects were randomized 3:1 (apixaban:placebo) within each IV dose cohort (0.5, 1.

Antithrombotic Effects of Combined PAR (Protease-Activated Receptor)-4 Antagonism and Factor Xa Inhibition.

Objective: PAR (protease-activated receptor)-4 antagonism has antiplatelet effects under conditions of high shear stress. We aimed to establish whether PAR4 antagonism had additive antithrombotic activity in the presence of factor Xa inhibition in an ex vivo model of acute arterial injury. Approach and Results: Fifteen healthy volunteers (29±6 years, 7 women) completed a phase zero double-blind randomized controlled crossover trial.

Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease.

Background: Compared with the general population, patients with advanced chronic kidney disease have a >10-fold higher burden of atrial fibrillation. Limited data are available guiding the use of nonvitamin K antagonist oral anticoagulants in this population.

Methods: We compared the safety of apixaban with warfarin in 269 patients with atrial fibrillation and advanced chronic kidney disease (defined as creatinine clearance [CrCl] 25 to 30 mL/min) enrolled in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation).