DOAC review report

A review of the clinical effectiveness of direct oral anticoagulants for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation

The following review summarises the published evidence on clinical effectiveness of direct acting oral anticoagulants (DOAC) for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF). In terms of safety outcomes, the review evaluates the risk of major bleeding events, intra-cranial haemorrhaging, and gastrointestinal (GI) bleeding in adult patients with NVAF who are taking oral anticoagulants.

The review included standard dose apixaban 5mg twice daily, dabigatran 150mg twice daily, edoxaban 60mg once daily, and rivaroxaban 20mg once daily. Lower dose edoxaban 30mg once daily and dabigatran 110mg twice daily were also included.

The pre-specified remit of this rapid review is to present clinical effectiveness evidence from published network meta-analyses, indirect treatment comparisons and mixed treatment comparisons, in relation to the DOACs and outcomes listed above. DOACs were not compared to warfarin or other oral a nticoagulants. This review is therefore based on several indirect comparisons using Bayesian statistics and has been briefly reviewed by a Bayesian statistician. The review is intended to inform clinical decision-making but not make specific recommendations.

Key points

  • No direct comparisons between DOACs were identified. Therefore this rapid review is based entirely on indirect evidence from published network meta-analyses.

Efficacy: stroke and systemic embolism prevention

  • The effects of apixaban 5mg, edoxaban 60mg and dabigatran 150mg on stroke and systemic embolism prevention were similar. Rivaroxaban 20mg was less effective than dabigatran 150mg.
  • In analysis of absolute risks, rather than relative risks, the absolute risk of stroke and systemic embolism for NVAF patients treated with a standard dose DOAC was lowest for dabigatran 150mg.

Safety: major bleeding, intra-cranial haemorrhage and gastrointestinal (GI) bleeding

  • Apixaban 5mg resulted in fewer major bleeding events than dabigatran 150mg or rivaroxaban 20mg. Edoxaban 60mg resulted in fewer major bleeding events than rivaroxaban 20mg.
  • The incidence of intra-cranial haemorrhage was similar for all standard dose DOACs. Apixaban 5mg resulted in fewer GI bleeding events than dabigatran 150mg or rivaroxaban 20mg.
  • In analysis of absolute risks, rather than relative risks, the absolute risk of major bleeding for NVAF patients treated with a standard dose DOAC was lowest in patients receiving apixaban 5mg.

Lower doses for special populations

  • Edoxaban 30mg was associated with more strokes and systemic embolisms than standard dose DOACs.
  • Edoxaban 30mg was associated with fewer major bleeding events than other DOACs and doses, and fewer GI bleeding events than all DOACs except apixaban 5mg.
  • Dabigatran 110mg and edoxaban 30mg resulted in fewer intra-cranial haemorrhages than rivaroxaban 20mg.
  • In analysis of absolute risks, rather than relative risks, the absolute risk of stroke and systemic embolism for NVAF patients treated with any DOAC dose was highest for edoxaban 30mg. The absolute risk of major bleeding in patients treated with any DOAC dose was lowest in patients taking edoxaban 30mg.

SUCRA scores

  • In SUCRA analyses, standard dose dabigatran 150mg had the highest probability of being the most effective DOAC for the prevention of stroke and systemic embolism. Apixaban 5mg was the standard dose DOAC with the highest probability of being associated with fewer major bleeding events.

Published Date: 23 June 2017