Warfarin vs DOACs in Afib: meta-analysis weighs the options

  • Lowenstern A & al.
  • Ann Intern Med
  • 30 Oct 2018

  • curated by Jenny Blair, MD
  • Clinical Essentials
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  • For thromboembolism prevention in patients with nonvalvular Afib, direct-acting oral anticoagulants (DOACs) are at least as safe, effective as warfarin (Coumadin).

Why this matters

  • Previous meta-analyses did not address subgroups or include intra-DOAC observational data. 

Key results

  • Warfarin vs dabigatran (Pradaxa; thrombin inhibitor):
    • RE-LY: Dabigatran outperforms warfarin for preventing stroke or systemic embolism (SSE); similar major bleeding, myocardial infarction, all-cause mortality (ACM) risks;
    • 35 observational studies: reduced stroke, SSE, hemorrhagic stroke.
  • Warfarin vs factor Xa inhibitors: 
    • ARISTOTLE: Apixaban (Eliquis) outperforms warfarin for stroke, systemic embolism, major bleeding, ACM;
    • ROCKET-AF: Rivaroxaban (Xarelto) noninferior to warfarin for SSE; 
    • ENGAGE-AF: Edoxaban (Savaysa) noninferior to warfarin for SSE.
  • Factor Xa inhibitors performed similarly in multiple subgroups.
  • Left atrial appendage closure (PROTECT AF, PREVAIL): 
    • Less major bleeding vs warfarin;
    • Noninferior to warfarin for stroke, ACM. 
  • Apixaban best cut bleeding in patients with lower renal function, dabigatran in patients aged  
  • Rivaroxaban and apixaban performed similarly in patients with stroke, diabetes, and heart failure.

Study design

  • Systematic review of 220 studies assessing stroke risk in Afib patients taking warfarin vs DOAC.
  • Funding: Patient-Centered Outcomes Research Institute.


  • Heterogeneous populations, outcomes.
  • No trials compared DOAC types, nor factor Xa inhibitors to each other.

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