Safety analysis of apixaban versus warfarin in patients with advanced kidney disease

Abstract

Anticoagulation in patients with advanced kidney disease, defined as those with an eGFR < 25 mL/min, including patients with end-stage renal disease on hemodialysis, remains an area of controversy and debate. Due to safety concerns regarding the increased risk for bleeding in this population, these patients have been excluded from all large-scale, randomized controlled trials to date. Warfarin and apixaban are both FDA-approved for use in this population and although warfarin remains the anticoagulant of choice, apixaban use is steadily increasing. This review combines relevant literature to better understand the risk versus benefit of anticoagulation in patients with severe kidney disease as well as the safety of apixaban versus warfarin in this population. High rates of bleed were found among both anticoagulants in those with severe kidney disease, suggesting that the risk for bleed associated with anticoagulation may not outweigh the benefit of treatment. Apixaban was found to be superior in rates of major bleed in those with ESRD on HD and may be superior to warfarin in those with an eGFR < 25 mL/min. However, large-scale, randomized clinical trials are needed to validate these results. With the continued development of novel agents there may be superior alternatives to apixaban and warfarin in those with severe kidney disease in the future.

Direct Oral Anticoagulant Use in Chronic Kidney Disease and Dialysis Patients With Venous Thromboembolism: A Systematic Review of Thrombosis and Bleeding Outcomes

“…This potential superiority of apixaban compared with warfarin in rates of major bleeding in those with ESKD or eGFR <25 mL/min/1.73 m 2 is consistent with results of another review assessing the safety of apixaban versus warfarin in patients with advanced kidney disease. 36 In regard to rivaroxaban, in a large observational cohort study, treatment with DOACs (majority using rivaroxaban), compared with warfarin, was not associated with an increased risk of major bleeding or all-cause mortality in the first 90 days of treatment. 37 This conclusion cannot be extended to all DOACs because the majority (95%) of DOACs used in this study was rivaroxaban.…”

Warfarin in nonvalvular atrial fibrillation—Time for a change?

“…58 Other retrospective studies confirmed these findings. Two subsequent meta-analyses, 59,60 which included smaller observational studies, [61][62][63][64] found that apixaban was associated with less major bleeding in HD patients with NVAF than warfarin with similar efficacy in prevention of stroke and systemic embolism. A recent systematic review concluded that in HD patients, compared to warfarin there was an increased risk of major bleeding with rivaroxaban (RR, 1.45; 95% CI, 1.09-1.93) and dabigatran (RR, 1.76; 95% CI, 1.44-2.15), while there was no difference between apixaban and warfarin.…”

Relevance of physicochemical properties and functional pharmacology data to predict the clinical safety profile of direct oral anticoagulants

“…In contrast, DOACs are associated with higher risks of gastrointestinal hemorrhage (GI) when compared to warfarin 9‐12 . There are concerns regarding other potentially serious ADRs linked with the DOAC drug class and significant mortality rates, such as liver impairment and central nervous system disorders 7,13‐18 …”