Non-vitamin K antagonist oral anticoagulants have better efficacy and equivalent safety compared to warfarin in elderly patients with atrial fibrillation: A systematic review and meta-analysis

Background: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in elderly patients (aged ≥75 years) with atrial fibrillation (AF), depending on dose and/or renal function. Methods: After systematically searching the databases (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), 5 phase III randomized controlled trials and reported data according to subgroups of elderly/non-elderly AF patients, comparing any NOACs and warfarin were included. The primary efficacy and safety outcomes were stroke/systemic thromboembolism and major bleeding. Results: (1) NOACs showed better efficacy than warfarin in elderly patients [RR 0.83 (0.69–1.00), p = 0.04, I² = 55%], but equivalent efficacy in non-elderly patients. (2) NOACs reduced major bleeding compared to warfarin in non-elderly (p < 0.001) and had comparable safety to warfarin in elderly patients. (3) Even in elderly patients with moderately impaired renal function, NOACs had a safety profile comparable to that of warfarin for major bleeding if dose reduction was reached appropriately [pooled RR 0.82 (0.35–1.88), p = 0.63, I² = 63%]. (4) All-cause mortality was lower with NOACs in non-elderly patients [RR 0.89 (0.83–0.95), p = 0.001, I² = 0%], and with standard-dose NOAC group of elderly patients [RR 0.93 (0.86–1.00), p = 0.04, I² = 0%] compared to warfarin. Conclusions: For elderly patients (aged ≥75 years), NOACs showed better efficacy and equivalent safety compared to warfarin even in those with moderately impaired renal function. All-cause mortality was lower with standard-dose NOACs compared to warfarin in the elderly patient group. Systematic review registration: The protocol of this meta-analysis was registered on PROSPERO under CRD42016047922 (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016047922).