Safety of apixaban compared to warfarin in hemodialysis patients: Do antiplatelets make a difference?

Data on the safety of apixaban compared to warfarin in hemodialysis (HD) patients are accumulating, but the impact of concomitant antiplatelet use is unknown. Compare hemorrhagic risk and impact of antiplatelets in HD patients receiving oral anticoagulants (OAC). Retrospective, multi-center study of HD patients started on OAC inpatient over 5 years. 707 patients were included: 563 received warfarin, and 144 received apixaban. 197 had bleeding, most in the warfarin group (173 [30.1%] vs 24 [16.7%] in the apixaban group), P-value < .01). However, with concomitant antiplatelet use, frequencies were similar (31.4% vs 25.0%; P-value = .292). Cumulative incidence using bleeding as event of interest and death as competing risk showed higher rates of bleeding with warfarin. In a multivariate model, apixaban was associated with a lower hemorrhagic risk (hazard ratio [HR] 0.55 [95% confidence interval {CI} 0.35-0.86}). Apixaban showed lower hemorrhagic risk alone (HR 0.24, 95% CI 0.10-0.55) and similar risk when administered with antiplatelets (HR 0.93, 95% CI 0.55-1.56). Apixaban is associated with less bleeding in HD patients compared to warfarin, but concomitant antiplatelet use may negate the safety advantage. Prospective trials are warranted to determine the impact of antiplatelets on apixaban safety.

Ionescu F ，Cooper C ，Petrescu I ，George J ，Mansuri S ... -  《-》

Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States.

Siontis KC ，Zhang X ，Eckard A ，Bhave N ，Schaubel DE ，He K ，Tilea A ，Stack AG ，Balkrishnan R ，Yao X ，Noseworthy PA ，Shah ND ，Saran R ，Nallamothu BK ... -  《-》

Clinical Application and Pharmacodynamic Monitoring of Apixaban in a Patient with End-Stage Renal Disease Requiring Chronic Hemodialysis.

Despite prescribing guidance, limited data exist to describe the use of apixaban in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). Current apixaban dosing recommendations for this patient population are based largely on a single-dose pharmacokinetic study of eight patients. We describe the clinical application and pharmacodynamic monitoring of apixaban in a 62-year-old 156-kg African-American woman with nonvalvular atrial fibrillation and ESRD requiring hemodialysis who developed calciphylaxis while receiving warfarin therapy. Based on a multidisciplinary clinical judgment decision due to concern for drug accumulation after multiple doses in patients with ESRD receiving HD, she was anticoagulated with apixaban 2.5 mg twice/day, as opposed to 5 mg twice/day as recommended by the package insert. Antifactor Xa monitoring was used, and resultant peak and trough apixaban concentrations were above the upper limit of detection for our clinical laboratory (more than 2.00 IU/ml). On day 7 of her hospitalization, the patient developed gastrointestinal bleeding, and apixaban was discontinued; no further clinical signs of bleeding occurred during her subsequent hospitalization course. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between apixaban exposure and the manifestation of gastrointestinal bleeding. The patient ultimately died 44 days after the acute bleeding event; however, coagulation concerns were not implicated in the patient's death. To our knowledge, this is the first case report that describes apixaban use and associated antifactor Xa monitoring in a patient with ESRD receiving HD, and it provides concern for current apixaban dosing recommendations in this patient population. Further pharmacokinetic and clinical data are likely necessary to better characterize apixaban use in these patients to optimize safety and efficacy.

Kufel WD ，Zayac AS ，Lehmann DF ，Miller CD ... -  《-》

Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin.

Brekelmans MP ，Scheres LJ ，Bleker SM ，Hutten BA ，Timmermans A ，Büller HR ，Middeldorp S ... -  《-》

Reprint of: Efficacy and safety of apixaban compared to warfarin for nonvalvular atrial fibrillation in end-stage renal disease on hemodialysis.

This study compared the efficacy and safety of apixaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and end-stage renal disease (ESRD) on hemodialysis (HD). Apixaban decreased incidence of stroke and bleeding compared with warfarin in major clinical trials that excluded patients with severe renal dysfunction. Apixaban is no longer contraindicated in patients with ESRD on HD with NVAF based on pharmacokinetic studies. Limited clinical data exist for patients with ESRD on HD on apixaban. A retrospective chart review was performed on patients with a diagnosis of NVAF and ESRD on HD who were prescribed apixaban or warfarin for stroke prevention in the years 2018 through 2019. Patients' charts were reviewed for up to a 2-year period. Patients on renal replacement therapy other than HD, those using anticoagulation for reasons other than NVAF, patients with Child-Pugh Class C cirrhosis, and those with severe mitral valve stenosis were excluded. The primary outcome was emergency department visits or hospital admissions for ischemic stroke or transient ischemic attack. Secondary outcomes included major or minor bleeding and adverse effects. A total of 181 patients were screened; 110 patients met eligibility criteria and were included in the analysis. Four patients (7.5%) in the apixaban group and 6 patients (10.5%) in the warfarin group met the primary outcome of hospitalization or emergency department visit for stroke (P = 0.742). Symptomatic bleeding occurred in 39.6% of patients in the apixaban group and 36.8% in the warfarin group (P = 0.918). A trend in major bleeding occurred more often in the warfarin group, 52.4% versus 49.2% (P = 0.758). There were no statistically significant differences in efficacy and safety outcomes between apixaban and warfarin in patients with NVAF and ESRD on HD in the intention-to-treat analysis of our study. Larger trials are needed to further analyze this patient population.

Moore M ，Vizcaino K ，Ewing JA ，St Ville M ... -  《-》