Fracture in Association with Anticoagulant Therapy in Patients with CKD and Atrial Fibrillation.

Key Points: In patients with CKD and atrial fibrillation, we observed no difference in the rates of fracture between initiators of direct oral anticoagulant and warfarin. However, direct oral anticoagulant use relative to warfarin was associated with a lower risk of all-cause mortality.

Background: Direct oral anticoagulant (DOAC) use has been associated with a lower risk of adverse events relative to warfarin in patients with atrial fibrillation. Little is known about the risk of fracture in association with anticoagulant therapy in patients with CKD.

Methods: We conducted a new user, active comparator cohort study in a United States-based commercial claims database spanning 2013 through 2020 to quantify the comparative risk of fracture associated with select DOACs (apixaban or rivaroxaban) versus warfarin. Individuals were required to have International Classification of Diseases diagnosis codes for CKD (stages 3–5) and atrial fibrillation during the 365-day baseline period before anticoagulant initiation. Primary analyses quantified nonvertebral fracture risk between patients initiating DOACs and warfarin using a 1:1 propensity score-matched design. Cox proportional hazards regression was used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) of nonvertebral fracture. Secondary analyses evaluated risks of hip fracture and all-cause mortality.

Results: The 1:1 propensity score-matched population included 14,370 DOAC initiators and 14,370 warfarin initiators. The mean age at anticoagulant initiation was 77 years, and 45% were female. The HR for nonvertebral fracture comparing DOACs with warfarin was 1.12 (95% CI, 0.95 to 1.32), and the corresponding incidence rate difference per 1000 person-years was 3.55 (95% CI, −1.67 to 8.76). The HR and incidence rate difference comparing DOACs with warfarin were 0.98 (95% CI, 0.68 to 1.41) and −0.13 (95% CI, −2.52 to 2.25), respectively, for hip fracture and 0.91 (95% CI, 0.85 to 0.98) and −17.23 (95% CI, −29.49 to −4.96), respectively, for all-cause mortality.

Conclusions: In patients with CKD and atrial fibrillation, we did not observe a difference in the rates of fracture between DOAC and warfarin initiators. DOAC use relative to warfarin was associated with a lower risk of all-cause mortality.