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

J Cardiol. 2018 Aug;72(2):105-112. doi: 10.1016/j.jjcc.2018.01.015. Epub 2018 Mar 5.


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 (

Keywords: Atrial fibrillation; Elderly; Meta-analysis; Non-vitamin K antagonist oral anticoagulants; Stroke.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Humans
  • Treatment Outcome
  • Warfarin / therapeutic use*


  • Anticoagulants
  • Warfarin