Direct Factor Xa inhibitor reduces coronary plaque progression in AF

Apixaban versus warfarin in evaluation of progression of atherosclerotic and calcified plaques (prospective randomized trial)

Literature - Win TT, Nakanishi R, Osawa K et al. - Am Heart J 2019,

Introduction and methods

It has been shown that use of warfarin (a vitamin K antagonist, VKA) increases vascular calcifications [1] resulting in an increase in CV events [2]. The effect of apixaban, a direct Factor Xa inhibitor, which has no interaction with vitamin K, on the progression of atherosclerotic plaques is unknown.

Coronary computed tomography angiography (CCTA) is a novel non-invasive test for detection and assessment of stenosis severity, anatomic quantification of atherosclerotic plaque phenotypes, plaque burden and ability to differentiate between plaque types [3]. The changes in anatomic plaque composition have been associated with increased plaque rupture, myocardial infarction and death [3].

This prospective, single-center, randomized, open label trial compared apixaban vs. warfarin on progression of coronary plaque composition and volume in non-valvular AF (NVAF) patients (n=56) with use of CCTA. Patients were randomized to receive warfarin (n=30) or apixaban (n=26) and underwent CTA at baseline and 1 year. Primary objective of the study was to examine the change in coronary artery calcification in apixaban vs. warfarin groups. Secondary objective was to examine the rate of incident plaque and quantitative changes of different plaque types and volumes in the 2 groups.

Main results

  • After multivariable adjustment, higher calcified plaque volume was observed in the warfarin group compared to the apixaban group (β₂=18.28; p=0.04). After further adjustment for baseline plaque volume, greater volume of total (β₂=28.54; p=0.03), low attenuation (corresponds to the lipid core of a vunerable plaque) (β₂=3.58; p=0.02) and calcified (β2=14.10; p=0.005) plaque progression was observed in those who took warfarin compared to those on apixaban.
  • There was a trend for greater plaque progression of all types of plaques (total, non-calcified, fibrous, fibro-fatty, low attenuation, calcified) in those on warfarin vs. those on apixaban.


This study showed that progression of coronary atherosclerotic, low attenuation and calcified plaques was lower in AF patients on apixaban compared to those on warfarin. These finding indicate that NVAF patients with co-existing coronary artery disease may benefit from use of apixaban vs. warfarin.


1. Lee J, Nakanishi R, Li D, et al. Randomized trial of rivaroxaban versus warfarin in the evaluation of progression of coronary atherosclerosis. Am Heart J. 2018 Aug 24. pii: S0002-8703(18)30249-7.

2. Schurgers LJ, Joosen IA, Laufer EM, et al. Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype. PloS one. 2012;7:e43229

3. Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary computed

tomography angiography and the likelihood of acute coronary events in mid-term followup. J Am Coll Cardiol. 2015;66(4):337-46.

Find this article online at Am Heart J

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