Safety of apixaban compared to warfarin in hemodialysis patients: Do antiplatelets make a difference?

Abstract

Background Data on the safety of apixaban compared to warfarin in hemodialysis (HD) patients are accumulating, but the impact of concomitant antiplatelet use is unknown. Objectives Compare hemorrhagic risk and impact of antiplatelets in HD patients receiving oral anticoagulants (OAC). Methods Retrospective, multi‐center study of HD patients started on OAC inpatient over 5 years. Results 707 patients were included: 563 received warfarin, and 144 received apixaban. 197 had bleeding, most in the warfarin group (173 [30.1%] vs 24 [16.7%] in the apixaban group), P‐value < .01). However, with concomitant antiplatelet use, frequencies were similar (31.4% vs 25.0%; P‐value = .292). Cumulative incidence using bleeding as event of interest and death as competing risk showed higher rates of bleeding with warfarin. In a multivariate model, apixaban was associated with a lower hemorrhagic risk (hazard ratio [HR] 0.55 [95% confidence interval {CI} 0.35‐0.86}). Apixaban showed lower hemorrhagic risk alone (HR 0.24, 95% CI 0.10‐0.55) and similar risk when administered with antiplatelets (HR 0.93, 95% CI 0.55‐1.56). Conclusions Apixaban is associated with less bleeding in HD patients compared to warfarin, but concomitant antiplatelet use may negate the safety advantage. Prospective trials are warranted to determine the impact of antiplatelets on apixaban safety.

The Role of Direct Oral Anticoagulants in Advanced Chronic Kidney Disease – Questions and Future directions

“…Our group recently reported findings from a retrospective analysis of bleeding rates in HD patients treated with either warfarin or apixaban [33]. We found a significantly lower bleeding propensity with apixaban use alone compared to warfarin alone, whereas concurrent antiplatelet therapy markedly reduced the difference (Figure 1).…”

“…Chiefly, analyses of bleeding risk with DOACs in CKD and HD patients have largely ignored the interaction of antiplatelets and anticoagulants, which has recently gained attention in the cardiovascular disease literature. As previously discussed, CKD and HD patients are underrepresented in these studies, but the importance of this issue is underscored by a high percentage of antiplatelet use (40%-50.6%) in our cohort and that of others [32,33]. In the RENAL-AF trial, the impact of antiplatelet therapy on bleeding, despite a high rate of use (40%), was not explored.…”

A Review of Direct Oral Anticoagulants in Patients With Stage 5 or End-Stage Kidney Disease

“…38,39 Of the 8 remaining retrospective studies, 4 reported efficacy data between DOAC therapy and warfarin, and only 1 found a difference in favor of DOAC therapy. 37,40,41,43 Additionally, Miao et al 46 reported no difference between apixaban and rivaroxaban. Despite a lack of efficacy data, safety outcomes favor DOAC use in patients with AF and CKD-5 or ESKD.…”

“…Despite a lack of efficacy data, safety outcomes favor DOAC use in patients with AF and CKD-5 or ESKD. 40,43,44 To date, no study has reported greater rates of bleeding with DOACs compared to warfarin. 40,43,44 Likewise, no single DOAC has been established as safer than any other in CKD-5 or ESKD, although most comparisons between DOACs are with apixaban and rivaroxaban.…”

“…The use of apixaban and warfarin in patients with AF or VTE on HD was evaluated by Ionescu et al 40 in a multicenter, retrospective inpatient chart review. The study evaluated 144 patients on apixaban and 563 on warfarin.…”