At standard doses, direct oral anticoagulants (DOACs) were associated with a reduced risk of systemic embolism and intracranial hemorrhage (ICH) when compared with warfarin, with a greater derived benefit at lower creatinine clearance (CrCl-down to 25 mL/min). Lower doses of DOACs were associated with increased overall mortality without a significant decrease in ICH and incident bleeding when compared with standard dose DOACs and warfarin, across all CrCl down to 25 mL/min.