Apixaban versus No Anticoagulation in Patients Undergoing Long-Term Dialysis with Incident Atrial Fibrillation

Abstract

Background and objectivesThe relative efficacy and safety of apixaban compared with no anticoagulation have not been studied in patients on maintenance dialysis with atrial fibrillation. We aimed to determine whether apixaban is associated with better clinical outcomes compared with no anticoagulation in this population.Design, setting, participants, & measurementsThis retrospective cohort study used 2012–2015 US Renal Data System data. Patients on maintenance dialysis with incident, nonvalvular atrial fibrillation treated with apixaban (521 patients) were matched for relevant baseline characteristics with patients not treated with any anticoagulant agent (1561 patients) using a propensity score. The primary outcome was hospital admission for a new stroke (ischemic or hemorrhagic), transient ischemic attack, or systemic thromboembolism. The secondary outcome was fatal or intracranial bleeding. Competing risk survival models were used.ResultsCompared with no anticoagulation, apixaban was not associated with lower incidence of the primary outcome: hazard ratio, 1.24; 95% confidence interval, 0.69 to 2.23; P=0.47. A significantly higher incidence of fatal or intracranial bleeding was observed with apixaban compared with no treatment: hazard ratio, 2.74; 95% confidence interval, 1.37 to 5.47; P=0.004. A trend toward fewer ischemic but more hemorrhagic strokes was seen with apixaban compared with no treatment. No significant difference in the composite outcome of myocardial infarction or ischemic stroke was seen with apixaban compared with no treatment. Compared with no anticoagulation, a significantly higher rate of the primary outcome and a significantly higher incidence of fatal or intracranial bleeding and of hemorrhagic stroke were seen in the subgroup of patients treated with the standard apixaban dose (5 mg twice daily) but not in patients who received the reduced apixaban dose (2.5 mg twice daily).ConclusionsIn patients with kidney failure and nonvalvular atrial fibrillation, treatment with apixaban was not associated with a lower incidence of new stroke, transient ischemic attack, or systemic thromboembolism but was associated with a higher incidence of fatal or intracranial bleeding.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_05_29_CJN11650919.mp3

Oral Factor Xa Inhibitors versus Warfarin for the Treatment of Venous Thromboembolism in Advanced Chronic Kidney Disease

“…However, the narrow therapeutic index, drug-drug interactions, drug-food interactions, and need for laboratory monitoring make alternatives such as the OFXai attractive options to evaluate. Furthermore, the net clinical benefit of oral anticoagulants including warfarin or apixaban in those with advanced CKD has come into question, specifically in the setting of stroke prevention with atrial fibrillation (AF) [ 24 – 28 ]. In one meta-analysis, oral anticoagulants, including warfarin, dabigatran, and rivaroxaban were not associated with a reduced risk of thromboembolism and were associated with an increased risk of bleeding in patients with AF and CKD [ 28 ].…”

“…Furthermore, the net clinical benefit of oral anticoagulants including warfarin or apixaban in those with advanced CKD has come into question, specifically in the setting of stroke prevention with atrial fibrillation (AF) [ 24 – 28 ]. In one meta-analysis, oral anticoagulants, including warfarin, dabigatran, and rivaroxaban were not associated with a reduced risk of thromboembolism and were associated with an increased risk of bleeding in patients with AF and CKD [ 28 ]. There remains a paucity of data evaluating anticoagulation therapy for treatment of acute VTE in the setting of advanced CKD stage IV or greater.…”

Direct Oral Anticoagulants in Atrial Fibrillation: Practical Considerations and Remaining Issues

“…• Evidence for using DOACs in ESRD and dialysis patients is emerging and, so far, has indicated a potential for benefit, [25][26][27] although negative results have also been reported. 28,29 Which Drug-Drug Interactions Are Relevant?…”

Anticoagulation in Patients with End-Stage Renal Disease and Atrial Fibrillation: Confusion, Concerns and Consequences

“…57 Table 2 summarizes the major studies investigating role of antiplatelet agent as aspirin, vitamin K antagonist as warfarin and DOAC as apixaban in ESRD patients with AF. 4,5,10,43,44,[57][58][59][61][62][63][64][65]…”

“…Similar trends were noticed for major bleeding and GI bleeding [ 57 ]. Table 2 summarizes the major studies investigating role of antiplatelet agent as aspirin, vitamin K antagonist as warfarin and DOAC as apixaban in ESRD patients with AF [ 4 , 5 , 10 , 43 , 44 , 57 - 59 , 61 - 65 ].…”