Safety and Efficacy of Apixaban vs Warfarin in Patients With Stage 4 and 5 Chronic Kidney Disease: A Systematic Review

Warfarin has been an anticoagulant of choice in patients with advanced Chronic Kidney Diseases (CKD) at stages 4 and 5 for decades, but with the advent of Novel Oral Anticoagulants (NOACs), there has been a sharp rise in their prescriptions. Among all NOACS, apixaban is the least reliant on kidney function and is a very popular choice for this patient population. However, being utilized extensively, most of the landmark trials evaluating the safety and efficacy of apixaban excluded patients with Creatinine Clearance (CrCl) <25mL/min/1.73 m2 or Serum Creatinine (SCr) ≥2.5mg/dL. Its approval for advanced CKD patients came from limited pharmacokinetic data only. We conducted a systematic review comparing the safety and efficacy of apixaban to warfarin in patients with stage 4 and 5 CKD and on dialysis. We queried major research literature databases, including MEDLINE, PubMed, PubMed Central (PMC), Cochrane Central, and ScienceDirect to find relevant articles without any time or language restrictions. After screening and quality checks, we identified 11 studies relevant to our research question, of which nine were retrospective cohort studies, one was a post-hoc analysis of a randomized controlled trial (RCT), and one was an RCT. The included studies had a total of 27,007 patients, with 4,335 patients taking apixaban and 22,672 on warfarin. The results indicate that the overall efficacy of apixaban was equivalent to warfarin for the prevention of stroke, systemic embolization, and recurrent venous thromboembolism, but apixaban showed an equivalent and, in some studies, better safety profile than warfarin concerning the occurrence of bleeding. Apixaban may hence be considered a reasonable alternative to warfarin in patients with Stage 4 or 5 CKD and receiving dialysis. In light of the reviewed articles, we conclude that apixaban has similar efficacy and somewhat superior safety profile to warfarin, with more randomized controlled trials required to add to the evidence.