Direct-Acting Oral Anticoagulants Versus Warfarin in Medicare Patients With Chronic Kidney Disease and Atrial Fibrillation

Abstract

<jats:sec> <jats:title>Background and Purpose:</jats:title> <jats:p>The comparative effectiveness of direct-acting oral anticoagulants, compared with warfarin, for risks of stroke/systemic embolism, major bleeding, or death have not been studied in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Medicare data from 2011 to 2017 were used to identify patients with stages 3, 4, or 5 chronic kidney disease and new atrial fibrillation who received a new prescription for warfarin, apixaban, rivaroxaban, or dabigatran. We estimated marginal hazard ratios with 95% CIs for the association of each direct-acting oral anticoagulant, compared with warfarin, for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>A total of 22 739 individuals met criteria (46.3% warfarin, 29.6% apixaban, 17.2% rivaroxaban, 6.9% dabigatran). Across the groups of anticoagulant users, mean age was 78.4 to 79.0 years; 50.3% to 51.4% were women, and 80.3% to 82.8% had stage 3 chronic kidney disease. In the as-treated analysis, for stroke/systemic embolism, hazard ratios, all compared with warfarin, were 0.70 (0.51–0.96) for apixaban, 0.80 (0.54–1.17) for rivaroxaban, and 1.15 (0.69–1.94) for dabigatran. For major bleeding, analogous hazard ratios were 0.47 (0.37–0.59) for apixaban, 1.05 (0.85–1.30) for rivaroxaban, and 0.95 (0.70–1.31) for dabigatran. There was no difference in the risk of all-cause mortality between the direct-acting oral anticoagulants and warfarin. Results of the intention-to-treat analysis were similar.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Apixaban, compared with warfarin, was associated with decreased risk of stroke/systemic embolism and major bleeding; risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin.</jats:p> </jats:sec>

Trends in the Prescription of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation: Results of the Polish Atrial Fibrillation (POL-AF) Registry

“…Medicare data showed that apixaban, compared with warfarin, was associated with a decreased risk of stroke or systemic embolism and major bleeding. Risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin in patients with impaired renal function [36]. In the present study, GFR < 60 mL/min/1.73 m 2 was a factor predisposing the choice of apixaban and diminishing the chance of using rivaroxaban or dabigatran.…”

Chronic Kidney Disease and Its Impact on a Prothrombotic State in Patients with Atrial Fibrillation

“…Appropriate anticoagulant therapy and frequent renal function monitoring are crucial in these patients [37]. Moreover, taking into account concomitant increased risk of bleeding in patients with CKD and reported kidney injury in patients on warfarin during excessive anticoagulation non-vitamin K oral anticoagulants (unless contraindicated), especially apixaban, could be preferred over vitamin K antagonists [38][39][40][41][42]. Left atrial appendage occlusion might be an option in patients with severe CKD who have contraindications to lifelong anticoagulant therapy [43].…”

A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant

“…14 Other primary literature investigating DOAC use in ESRD has used warfarin as a comparator, which represents a limitation for these data. [15][16][17][18][19] As such, clinicians should be cautious when contemplating the use of anticoagulation for primary prevention of stroke in this population.…”

“…[20][21][22][23] Among the DOAC class, apixaban seems to be the safest and best tolerated agent in ESRD, which is intuitive given its low renal clearance. 15,16 Retrospective analyses comparing apixaban to warfarin in CKD stage IV, V, or dialysis suggest that it is at least as efficacious as warfarin in preventing thromboembolic events with significantly less major bleeding in some analyses. 16 Mixed data have been reported addressing rivaroxaban safety compared to warfarin in ESRD, with prospective data indicating a reduced risk of major bleeding, and retrospective data indicating an increased risk of death or hospitalization from bleeding.…”