Treatment with apixaban vs warfarin was associated with a greater reduction in the risk for major bleeding in patients with end-stage kidney disease (ESKD) undergoing dialysis with atrial fibrillation (AF), according to a study published in Circulation. In addition, a 5-mg dose of apixaban appears to be superior to a 2.5-mg dose in reducing the risk for stroke/systemic embolism and mortality in this patient population.
Medicare beneficiaries with ESKD and AF or atrial flutter who were included in the United States Renal Data System between 2010 and 2015 were enrolled (N=25,523) in the study. Investigators retrospectively compared patients treated with either apixaban (n=2351) or warfarin (n=23,172) in terms of major bleeding risk, survival free of stroke or systemic embolism, gastrointestinal bleeding, intracranial bleeding, and mortality. Subgroup analyses were also performed between the two treatment strategies with regard to age (≥75 or <75), sex, diabetes diagnosis, cerebrovascular accident or major bleeding history, obesity, modality of dialysis, and potential interacting medications.
Patients treated with apixaban had a significantly lower risk for major bleeding compared with patients treated with warfarin (hazard ratio [HR], 0.72; 95% CI, 0.59-0.87; P <.001). Despite this difference, apixaban did not confer a lower risk for stroke/systemic embolism compared with warfarin (HR, 0.88; 95% CI 0.69-1.12; P =.29).
In addition, a twice-daily 5-mg apixaban dose was associated with a reduced risk for stroke/systemic embolism (HR, 0.64; 95% CI, 0.42-0.97; P =.04) and mortality (HR, 0.63; 95% CI, 0.46-0.85; P =.003) compared with warfarin. In addition, a twice-daily 5-mg dose of apixaban demonstrated a lower risk for stroke/systemic embolism (HR, 0.61; 95% CI, 0.37-0.98; P =.04) and mortality (HR, 0.64; 95% CI, 0.45-0.92; P =.01) than twice daily 2.5-mg apixaban in a sensitivity analysis.
Limitations of the analysis included the lack of data on treatment adherence, as well as the relatively small number of patients on peritoneal dialysis.
The investigators suggested that “future clinical trials are therefore needed to assess whether focusing on stroke reduction using apixaban or warfarin is worth the elevated risks of bleeding in this specific setting.”
Siontis KC, Zhang X, Eckard A, et al. Outcomes associated with apixaban use in end-stage kidney disease patients with atrial fibrillation in the United States [published online June 28, 2018]. Circulation. doi:10.1161/CIRCULATIONAHA.118.035418