Safety and efficacy of apixaban versus low-molecular weight heparin or vitamin-K antagonists for venous thromboembolism treatment in patients with severe renal failure: A systematic review and meta-analysis

Introduction: Chronic kidney disease is an independent risk factor for venous thromboembolism (VTE). Traditionally, Low Molecular Weight Heparin (LMWH) followed by warfarin has been the conventional therapy for VTE treatment. Direct oral anticoagulants (DOACs), including apixaban, have shown several advantages over the traditional therapy in individuals with normal kidney function. This meta-analysis aims to review the safety and efficacy of apixaban compared to warfarin or LMWH for the treatment of VTE in severe renal failure.

Method: We conducted literature search in PubMed, Embase, and Cochrane databases. Retrospective observational studies involving clinical effectiveness and safety outcomes of apixaban compared to warfarin in adult patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/m² or on dialysis were included.

Results: Eight studies were included in the analysis. Significant reduction in VTE recurrence observed in apixaban compared to warfarin (RR, 0.65; 95 % CI, 0.43-0.98; P = 0.04; I2 = 78 %). No significant difference in all-cause mortality between apixaban and warfarin (RR, 0.99; 95 % CI, 0.91-1.07; P = 0.74; I2 = 0 %). Apixaban showed a significantly lower rate of major bleeding (RR, 0.72; 95 % CI, 0.62-0.84; P < 0.0001; I2 = 34 %) and minor bleeding events (RR, 0.42; 95 % CI, 0.21-0.86; P = 0.02; I2 = 10 %) compared to warfarin. No significant difference observed in clinically relevant non-major bleeding between apixaban and warfarin (RR, 0.81; 95 % CI, 0.65-1.00; P = 0.05; I2 = 67 %).

Conclusion: Apixaban was favored over warfarin for treating VTE in severe renal failure, reducing VTE recurrence and bleeding risk. No differences were observed in all-cause mortality and CRNMB events. More evidence is required due to limited RCTs and prospective studies.