Comparative safety and effectiveness of direct oral anticoagulants in patients with atrial fibrillation in clinical practice in Scotland

Br J Clin Pharmacol. 2019 Feb;85(2):422-431. doi: 10.1111/bcp.13814. Epub 2018 Dec 18.

Abstract

Aims: The aim of this study was to compare the clinical effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) in routine clinical practice.

Methods: This retrospective cohort study used linked administrative data. The study population (n = 14 577) included patients with a diagnosis of AF (confirmed in hospital) who initiated DOAC treatment in Scotland between August 2011 and December 2015. Multivariate Cox proportional hazard models were used to estimate hazard ratios of thromboembolic events, mortality and bleeding events.

Results: No differences between the DOACs were observed with regard to the risk of stroke, systemic embolism or cardiovascular death. In contrast, the risk of myocardial infarction was higher among patients prescribed apixaban in comparison to those on rivaroxaban (HR 1.67, 95% CI 1.02-2.71), and all-cause mortality was higher among rivaroxaban patients in contrast to both apixaban (1.22 [1.01-1.47]) and dabigatran (1.55 [1.16-2.05]) patients; rivaroxaban patients also had a higher risk of pulmonary embolism than apixaban patients (5.27 [1.79-15.53]). The risk of other major bleeds was higher among rivaroxaban patients compared to apixaban (1.50 [1.10-2.03]) and dabigatran (1.58 [1.01-2.48]) patients; the risks of gastrointestinal bleeds and overall bleeding were higher among rivaroxaban patients than among apixaban patients (1.48 [1.01-2.16] and 1.52 [1.21-1.92], respectively).

Conclusions: All DOACs were similarly effective in preventing strokes and systemic embolisms, while patients being treated with rivaroxaban exhibited the highest bleeding risks. Observed differences in the risks of all-cause mortality, myocardial infarction and pulmonary embolism warrant further research.

Keywords: DOAC; anticoagulants; atrial fibrillation; clinical effectiveness; safety.

Publication types

  • Comparative Study
  • 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*
  • Atrial Fibrillation / mortality
  • Dabigatran / administration & dosage
  • Dabigatran / adverse effects
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology*
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Embolism / epidemiology*
  • Pulmonary Embolism / etiology
  • Pulmonary Embolism / prevention & control
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyridones / administration & dosage
  • Pyridones / adverse effects
  • Retrospective Studies
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / adverse effects
  • Scotland / epidemiology
  • Stroke / epidemiology*
  • Stroke / etiology
  • Stroke / prevention & control
  • Treatment Outcome

Substances

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