PHARMACOKINETIC AND PHARMACODYNAMIC VARIABILITY OF DIRECT ORAL ANTICOAGULANTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE: IMPLICATIONS FOR PERSONALIZED DOSING: A SYSTEMATIC REVIEW

Abstract

Background: Anticoagulation in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) presents unique challenges due to altered pharmacokinetics, pharmacodynamics, and heightened risks of both thrombosis and bleeding. Direct oral anticoagulants (DOACs) offer practical advantages over warfarin, but their safety and efficacy in this population remain debated.

Objectives: This systematic review aimed to evaluate the pharmacokinetic and pharmacodynamic variability of DOACs in patients with CKD and ESRD and to explore implications for personalized dosing.

Methods: Following PRISMA 2020 guidelines, a systematic search of PubMed, Embase, Scopus, Web of Science, and grey literature sources was conducted. Eleven eligible studies were included, comprising randomized controlled trials, cohort studies, and pharmacokinetic investigations involving adult patients with atrial fibrillation or venous thromboembolism and CKD/ESRD. Data extraction covered study characteristics, interventions, pharmacokinetic/pharmacodynamic findings, and clinical outcomes. Risk of bias was assessed using validated tools.

Results: Across the eleven included studies, dabigatran and rivaroxaban showed increased bleeding risks in dialysis populations, while apixaban demonstrated a more favorable safety profile with similar or improved efficacy compared with warfarin. Pharmacokinetic studies revealed significant drug accumulation in impaired renal function and limited clearance during dialysis, underscoring the need for dose adjustment. Observational evidence suggested potential benefits of standard-dose apixaban over reduced dosing and warfarin, though variability in study designs limited comparability.

Conclusions: Apixaban may represent the most promising DOAC for patients with advanced CKD and ESRD; however, substantial variability in drug exposure highlights the importance of individualized dosing. Further research is essential to optimize anticoagulation strategies and improve outcomes in this high-risk population.