Long-term comparative efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation and chronic kidney disease: A nationwide observational study.

BACKGROUND

Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) face an increased risk of both thromboembolic and bleeding events, making anticoagulation management challenging.

OBJECTIVE

This study aimed to compare the efficacy and safety of direct oral anticoagulants (DOACs), warfarin, and no oral anticoagulation (OAC) in patients with AF and CKD.

METHODS

Using data of 18,980 AF patients with CKD from Clalit database, we compared OAC vs no OAC and DOACs vs warfarin. Primary endpoints were composite-safety (intracranial hemorrhage, gastrointestinal bleeding) and efficacy (ischemic stroke, myocardial infarction, embolism, all-cause mortality).

RESULTS

OAC therapy was associated with a lower risk of the primary composite efficacy outcome compared with no OAC (hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.52-0.62), driven by reduced all-cause mortality (HR: 0.32, 95% CI: 0.29-0.36), with no significant differences in thromboembolic events or bleeding outcomes. In the comparison of DOACs vs warfarin, warfarin was associated with higher rates of composite bleeding (HR: 0.67, 95% CI: 0.5-0.89) and intracranial hemorrhage (HR: 0.51, 95% CI: 0.32-0.8). DOACs were associated with a lower risk of the primary composite efficacy outcome (HR: 0.84, 95% CI: 0.74-0.95), with no significant differences in ischemic stroke. Among appropriately anticoagulated patients, safety differences between DOACs and warfarin were no longer significant (composite bleeding HR: 0.87, 95% CI: 0.52-1.47); however, DOACs remained associated with fewer primary efficacy events (HR: 0.75, 95% CI: 0.60-0.94).

CONCLUSION

In patients with AF and CKD, OAC therapy improved efficacy outcomes without increasing bleeding risk. DOACs were more effective and safer than warfarin, supporting their use as the preferred anticoagulant in this high-risk population. Appropriate dosing and therapeutic monitoring are essential to maximize benefits and minimize bleeding complications.