Treatment Effect of NOAC Vs Wafarin in AF Shows Generally Consistent Stroke Rates Across the Spectrum of BMI and Body Weight

A study analysing the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) suggests a generally consistent treatment effect in patients with atrial fibrillation (AF) when compared to warfarin, though there remain uncertainties at high BMI and BW. 




  • The COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) study pooled patient-level data from 4 pivotal randomized trials of NOACs versus warfarin in patients with AF (ROCKET AF, RE-LY, ARISTOTLE and ENGAGE-TIMI AF).
  • 58,464 patients were included in the study, with a median BMI of 28.3 (interquartile range, 25.2 – 32.2) kg/m2, and the median body weight was 81.0 (interquartile range, 70.0-94.3) kg. 
  • A Cox proportional hazards model stratified by trial to account for heterogeneity between trials and was used to examine outcomes across BMI and BW. 
  • The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was ISTH major bleeding. 





  • Event probability of stroke or systemic embolism was found to be lower at a higher BMI regardless of the treatment patients were receiving.
  • The likelihood of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with a NOAC. 
  • Overall, NOACs were found to reduce stroke and systemic embolism (HRadj, 0.80 [95% CI, 0.73–0.88]; P<0.001) with a generally consistent effect across BMI (P for trend across HRs, 0.48). NOACs reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82–0.94]; P<0.001), with reduced benefit in patients at a higher BMI (Ptrend , 0.003). 
  • The treatment effects for secondary outcomes were also consistent across BMI except for net clinical outcome and death, which although reduced overall with NOACs favoured warfarin at higher BMIs. 


The COMBINE AF investigators summarised these findings stating that “the treatment effect of NOAC versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated at a higher BMI and BW. Death and the net clinical outcome are reduced with NOACs versus warfarin overall, although there remain uncertainties for these outcomes at a very high BMI and BW”.


This systematic review was sponsored by Duke Clinical Research Institute. 



Patel, S, Braunwald, E, Steffel, J, et al. Efficacy and Safety of Non–Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of Four Randomized Clinical Trials of 58 464 Patients With Atrial Fibrillation. Circulation. E-pub: 24 Jan 2024. Accessed 21 February 2024.