Non-vitamin K Antagonist Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation

Elderly and frail patients with atrial fibrillation (AF) are at increased risk of thrombotic events, bleeding, and death compared to their counterparts, making their management challenging. With the introduction of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in the past decade, the risk:benefit balance in such high-risk patients with AF has tipped in favor of treating these patients with anticoagulation, and in most cases with a NOAC instead of a VKA. In patients ≥75 years of age with AF, each of the 4 approved NOACs reduced stroke or systemic embolism and vs warfarin in their landmark clinical trial and lowered mortality. However, only apixaban and edoxaban significantly reduced major bleeding vs warfarin. A similar pattern was seen in even older cohorts (≥80 and ≥85 years). Among patients age ≥80 who are not candidates for oral anticoagulants at the approved dose, edoxaban 15 mg may be a reasonable alternative. In elderly or frail individuals who are on multiple comedications (particularly if ≥1 moderate or strong cytochrome P-450 inhibitor), only edoxaban consistently reduced major bleeding compared to warfarin. Regardless of the specific OAC selected, appropriate dosing in the elderly (who frequently qualify for dose reduction per the prescribing label) is critical. In elderly and frail patients with AF, factors that may modify the efficacy-safety profile of specific oral OACs should be carefully considered to permit the optimal selection and dosing in these vulnerable patients.