van Rein N, et al. - In this nationwide cohort study of Danish patients, researchers assessed incidence rates (IRs) of major bleeding and hazard ratios overall, and by treatment modality, age, CHA₂DS₂-VASc score, and comorbidity. Participants were 272,315 atrial fibrillation patients (≥50 years of age) who did not receive anticoagulant treatment, and were treated with vitamin K antagonists, direct oral anticoagulants, platelet inhibitors, or combinations of antithrombotic drugs. Major bleeding was defined as bleeding requiring hospitalization or causing death. They performed a follow-up of 1,373,131 patient-years (PYs), during which, the occurrence of 31,459 major bleeds was noted. Findings revealed that compared with patients on dual therapy or monotherapy, high rates of major bleeding were seen in patients with atrial fibrillation on triple therapy. In patients on triple therapy >90 years of age or with a CHA₂DS₂-VASc score >6 or with a history of a major bleeding, high bleeding rates require careful consideration of such therapy in these patients.