Please login or register to print this page.

Clinical Articles, Lead Article

NOAC stroke protection in AF cuts across subgroups

Four new oral anticoagulants (NOACs) protect against stroke or systemic embolism better than warfarin, comparing favourably on safety in patients with atrial fibrillation (AF), according to a study1 published recently in The Lancet.

Authors led by Dr Christian Ruff (Brigham and Women’s Hospital and Harvard Medical School, Boston, USA) assessed the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. Their meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with AF.

The authors searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with AF who were randomised to receive NOACs or warfarin, and trials in which both efficacy and safety outcomes were reported. They did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF—TIMI 48 trials.

Ruff, Christian MD

Dr Christian Ruff (Brigham and Women’s Hospital and Harvard Medical School, USA)

The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. They calculated relative risks (RRs) and 95% CIs for each outcome, and did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. The authors also used a random-effects model to compare pooled outcomes and tested for heterogeneity.

42,411 participants received a NOAC and 29,272 participants received warfarin. NOACs significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0.81, 95% CI 0.73—0.91; p<0.0001), mainly driven by a reduction in haemorrhagic stroke (0.49, 0.38—0.64; p<0.0001). New oral anticoagulants also significantly reduced all-cause mortality (0.90, 0.85—0.95; p=0.0003) and intracranial haemorrhage (0.48, 0.39—0.59; p<0.0001), but increased gastrointestinal bleeding (1.25, 1.01—1.55; p=0.04).

They noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with NOACs when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0.69, 0.59—0.81 vs 0.93, 0.76—1.13; p for interaction 0.022). Low-dose NAOC regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1.03, 0.84—1.27; p=0.74), and a more favourable bleeding profile (0.65, 0.43—1.00; p=0.05), but significantly more ischaemic strokes (1.28, 1.02—1.60; p=0.045).

NOACs had a favourable risk—benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding the authors found. The relative efficacy and safety of NOACs was consistent across a wide range of, they concluded.


1. Ruff CT, Giugliano RP Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2013. Published online ahead of print.

Published on: December 20, 2013

Members Area

Log in or Register now.

 For healthcare professionals only
Angina book sky



Subscribe to our RSS feed


Sign up for our regular email newsletters & be the first to know about fresh articles and site updates.


    None Found


  • ArrhythmiaAlliance
  • Stars
  • Anticoagulation Europe
  • Atrial Fibrillation Association

You are not logged in

You need to be a member to print this page.
Sign up for free membership, or log in.

You are not logged in

You need to be a member to download PDF's.
Sign up for free membership, or log in.