Anticoagulant safety in people with advanced kidney disease and atrial fibrillation

There is a high prevalence of atrial fibrillation (AF) in people with advanced chronic kidney disease (CKD). People with CKD have a higher risk for thromboembolic complications of AF, as well as higher risk of bleeding, compared with people with healthy kidneys. 

Anticoagulants that are used to reduce the risk of stroke in people with AF include warfarin and direct oral anticoagulants, such as apixaban and rivaroxaban. Despite being at high risk for both stroke and bleeding, evidence to guide anticoagulant treatment in people with advanced CKD and AF is lacking. The present study set out to compare the safety and effectiveness of warfarin or apixaban (2.5 or 5 mg twice daily) versus rivaroxaban (≤15 or 20 mg once daily) in this population. 

Data from two large health insurance databases in the US were used to construct two active-comparator cohorts of patients: newly initiated warfarin vs apixaban (n=12,488), and rivaroxaban vs apixaban (n=5,720). Baseline characteristics were well-balanced in both cohorts after propensity-score matching. Eligible individuals must have been free of any anticoagulant use in the preceding year, have non-valvular AF or flutter and have two diagnosis codes for CKD stages 4 or 5 without dialysis. People with recent venous thromboembolic or major bleeding events were excluded.

The incidence rate for major bleeding for warfarin initiators was 102.7 per 1000 person-years, compared to 50.7 for apixaban initiators (adjusted HR, 1.85 [95% CI, 1.59–2.15]). This included major gastrointestinal bleeding (1.86 [1.53–2.25]) and intracranial bleeding (2.15 [1.42–3.25]). Rivaroxaban was also associated with a higher rate of major bleeding than apixaban, with incidence rates of 96.1 and 52.8 per 1000 person-years, respectively (1.69 [1.33–2.15]).

All-cause mortality was similar for warfarin (1.08 [0.98–1.18]) and rivaroxaban (0.94 [0.81–1.10]), compared to apixaban. There were no statistically significant differences for ischaemic stroke between warfarin (1.14 [0.83–1.57]) or rivaroxaban (0.71 [0.40–1.24]), compared to apixaban, although few events were recorded.

The authors conclude that these findings suggest that apixaban has a better safety profile than either warfarin or rivaroxaban in people with non-valvular AF and advanced CKD who are not yet on dialysis.

The full article can be read here.