Direct Oral Anticoagulants Versus Vitamin K Antagonists in Real-life Patients With Atrial Fibrillation. A Systematic Review and Meta-analysis

Rev Esp Cardiol (Engl Ed). 2019 Apr;72(4):305-316. doi: 10.1016/j.rec.2018.03.009. Epub 2018 Mar 30.
[Article in English, Spanish]


Introduction and objectives: To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation.

Methods: A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA statement. The ROBINS-I tool was used to assess risk of bias.

Results: A total of 27 different studies publishing data in 30 publications were included. In the studies with a follow-up up to 1 year, apixaban (HR, 0.93; 95%CI, 0.71-1.20) and dabigatran (HR, 0.95; 95%CI, 0.80-1.13) did not significantly reduce the risk of ischemic stroke vs warfarin, whereas rivaroxaban significantly reduced this risk (HR, 0.83; 95%CI, 0.73-0.94). Apixaban (HR, 0.66; 95%CI, 0.55-0.80) and dabigatran (HR, 0.83; 95%CI, 0.70-0.97) significantly reduced the major bleeding risk vs warfarin, but not rivaroxaban (HR, 1.02; 95%CI, 0.95-1.10), although with a high statistical heterogeneity among studies. Apixaban (HR, 0.56; 95%CI, 0.42-0.73), dabigatran (HR, 0.45; 95%CI, 0.39-0.51), and rivaroxaban (HR, 0.66; 95%CI, 0.49-0.88) significantly reduced the risk of intracranial bleeding vs warfarin. Reduced doses of direct oral anticoagulants were associated with a slightly better safety profile, but with a marked reduction in stroke prevention effectiveness.

Conclusions: Data from this meta-analysis suggest that, vs warfarin, the stroke prevention effectiveness and bleeding risk of direct oral anticoagulants may differ in real-life patients with atrial fibrillation.

Keywords: Anticoagulantes orales directos; Apixaban; Apixabán; Atrial fibrillation; Clinical practice; Dabigatran; Dabigatrán; Direct oral anticoagulants; Fibrilación auricular; Meta-analysis; Metanálisis; Práctica clínica; Rivaroxaban; Rivaroxabán; Warfarin; Warfarina.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Atrial Fibrillation / complications*
  • Brain Ischemia / prevention & control*
  • Case-Control Studies
  • Dabigatran / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Observational Studies as Topic
  • Pyrazoles / administration & dosage
  • Pyridones / administration & dosage
  • Risk Factors
  • Rivaroxaban / administration & dosage
  • Stroke / prevention & control*
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors*
  • Warfarin / administration & dosage


  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • Vitamin K
  • apixaban
  • Warfarin
  • Rivaroxaban
  • Dabigatran