Apixaban 5 mg vs 2.5 mg and Higher Bleeding Risk in Atrial Fibrillation With CKD

Among patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD), 5-mg apixaban twice daily, compared with 2.5-mg apixaban twice daily, is associated with an increased risk for bleeding, researchers reported in Circulation.

The retrospective cohort study used data from the Optum Labs Data Warehouse to assess the risk for bleeding and stroke/systemic embolism associated with 2 apixaban dosages in adult patients with AF and nondialysis-dependent CKD stage 4/5. Patients initiated apixaban use from January 1, 2013, to December 31, 2021.

Stabilized inverse probability of treatment weighting (IPTW) with propensity score was used to account for differences in baseline characteristics between the groups.

The cohort included 4313 patients, of whom 40% (n=1705) started with a dose of 5 mg twice daily and 60% (n=2608) with a dose of 2.5 mg twice daily. In the unweighted analyses, participants who received the 5-mg dose were younger (mean age, 72 vs 80 years), had an increased body weight (95 vs 80 kg), and had a higher serum creatinine level (2.7 vs 2.5 mg/dL) compared with those who received the 2.5-mg dose.

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A bleeding-related hospitalization occurred in 61 (4%) patients on the 5-mg dose vs 81 (3%) on the 2.5-mg dose during a median follow-up of 8 (IQR, 4-15) months. Treatment with the 5-mg dose was significantly associated with an increased risk for any bleeding vs the 2.5-mg dose, with an absolute risk difference of 3.1% during a 2-year follow-up, according to the IPTW analyses. The increased bleeding risk associated with 5-mg apixaban was consistent for all subgroups (all P_interaction ≥.10).

Stroke or systemic embolism occurred in 39 (2%) patients in the 5-mg dose group vs 86 (3%) in the 2.5-mg dose group. In the IPTW analyses, the risk for stroke/systemic embolism was not different based on apixaban dose (incidence rate difference, 0.2 [95% CI, -1.0 to 1.4] events per 100 person-years; subdistribution hazard ratio, 1.01 [95% CI, 0.59-1.73]). The findings were consistent in subgroup analyses (all P_interaction ≥.10).

Mortality was reported in 116 patients (7%) in the 5-mg dose group vs 288 (11%) in the 2.5-mg dose group. In the IPTW analyses, no statistical differences were found between the 2 groups in mortality risk (5 mg vs 2.5 mg dose: incidence rate difference, 0.5 [95% CI, -1.6 to 2.6] events per 100 person-years; hazard ratio, 1.03 [95% CI, 0.77-1.38]).

Limitations of the study include medication use based on prescriptions, as well as potential residual confounding. Also, the follow-up was relatively short, and few major bleeding events occurred in both dose groups, which could limit the statistical power.

“These findings suggest that 2.5-mg apixaban may be a better choice than 5 mg for patients with AF and severe CKD, supporting the KDIGO [Kidney Disease: Improving Global Outcomes] guidelines’ dosing suggestion for this population and apixaban dosing recommendations based on kidney function by [the] European Medicines Agency, which differ from those issued by the US Food and Drug Administration,” wrote the researchers.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Xu Y, Chang AR, Inker LA, McAdams-DeMarco M, Grams ME, Shin J-I. Associations of apixaban dose with safety and effectiveness outcomes in patients with atrial fibrillation and severe chronic kidney disease. Circulation. Published online September 8, 2023. doi: 10.1161/CIRCULATIONAHA.123.065614

This article originally appeared on The Cardiology Advisor