Abstract
BACKGROUND: Older age increases the risk of thromboembolism (TE) and major bleeding in atrial fibrillation (AF) patients, but limited evidence exists regarding the older population (age ≥ 80) especially from different global regions. Data on benefits of oral anticoagulants in these very old individuals are also limited. METHODS: From the prospective, multicenter Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation registry, we analysed by age all-cause death, cardiovascular death, major adverse cardiovascular events (MACE), TE, major bleeding, stroke, and myocardial infarction (MI) over 3-years follow-up. RESULTS: Of 7652 patients aged ≥75 years (age 80.1 ± 3.9 years, 47.1% male), 4006 were ≥ 80 years (age 83.4 ± 3.9 years, 43.5% male). After multivariable adjustment, older patients had a higher risk of all-cause death (HR:1.94, 95% CI: 1.67-2.27), cardiovascular death (HR: 2.17, 95% CI: 1.71-2.74), MACE (HR: 1.57, 95% CI: 1.32-1.86), TE (HR: 1.45, 95% CI: 1.14-1.83), major bleeding (HR: 1.30, 95% CI: 1.04-1.63), stroke (HR: 1.38, 95% CI: 1.06-1.80) and MI (HR: 1.59, 95% CI:1.14-2.22). Compared with VKA, NOAC use in patients ≥80 years was associated with lower risks of all-cause death (HR: 0.79, 95% CI: 0.65-0.97), cardiovascular death (HR: 0.70, 95% CI: 0.51-0.96), MACE (HR: 0.72, 95% CI: 0.56-0.92), and major bleeding (HR: 0.66, 95% CI: 0.48-0.92). NOACs were more beneficial than warfarin for mortality, MACE and major bleeding in frail patients. The risk of clinical events associated with older patients was primarily seen in Europe and Asia (p-interaction > 0.05), but the effectiveness and safety of NOACs vs. warfarin was consistent across regions. CONCLUSIONS: Older age was independently associated with higher risk of death, major bleeding, TE and MACE. Compared with VKA, NOACs show improved effectiveness and safety in the older and patients with frailty, with similar efficacy across regions and ethnic groups.