Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study

J Intern Med. 2018 Jan;283(1):45-55. doi: 10.1111/joim.12683. Epub 2017 Sep 21.

Abstract

Background: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF).

Objective: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients.

Methods: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula).

Results: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%).

Conclusions: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.

Keywords: NOAC; apixaban; atrial fibrillation; dabigatran; dose; rivaroxaban.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Cohort Studies
  • Dabigatran* / administration & dosage
  • Dabigatran* / adverse effects
  • Denmark
  • Dose-Response Relationship, Drug
  • Female
  • Hemorrhage* / chemically induced
  • Hemorrhage* / prevention & control
  • Humans
  • Male
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Registries
  • Rivaroxaban* / administration & dosage
  • Rivaroxaban* / adverse effects
  • Stroke* / etiology
  • Stroke* / prevention & control

Substances

  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
  • Dabigatran