Biomarker | VKA treatment before randomisation | Apixaban | Warfarin | Apixaban vs warfarin ratio geometric mean (95% CI) | Treatment difference P values | ||

Month 2/baseline geometric mean (95% CI) | Month 2 concentration geometric mean (95% CI) | Month 2/baseline geometric mean (95% CI) | Month 2 concentration geometric mean (95% CI) | ||||

F1+2 (pmol/L) | No (n=1939) | 0.75 (0.70 to 0.80) | 130.1 (121.8 to 138.9) | 0.41 (0.38 to 0.43) | 70.8 (66.1 to 75.8) | 1.84 (1.67 to 2.02) | <0.0001 |

Yes (n=2879) | 1.41 (1.34 to 1.48) | 116.1 (110.5 to 122.0) | 0.63 (0.60 to 0.66) | 51.7 (49.2 to 54.4) | 2.24 (2.09 to 2.41) | <0.0001 | |

D-dimer (µg/L) | No (n=1939) | 0.77 (0.74 to 0.80) | 488.1 (471.1 to 505.9) | 0.62 (0.60 to 0.64) | 392.6 (378.2 to 407.5) | 1.24 (1.18 to 1.31) | <0.0001 |

Yes (n=2881) | 1.10 (1.07 to 1.12) | 461.8 (450.5 to 473.3) | 0.89 (0.86 to 0.91) | 373.0 (363.9 to 382.3) | 1.24 (1.20 to 1.28) | <0.0001 | |

sCD40L (µg/L) | No (n=1939) | 1.09 (1.04 to 1.14) | 0.63 (0.60 to 0.66) | 1.07 (1.02 to 1.12) | 0.62 (0.59 to 0.65) | 1.02 (0.95 to 1.09) | 0.5531 |

Yes (n=2880) | 1.05 (1.01 to 1.09) | 0.55 (0.53 to 0.58) | 1.07 (1.03 to 1.11) | 0.56 (0.54 to 0.59) | 0.98 (0.93 to 1.03) | 0.4931 | |

vWF antigen (kIE/L) | No (n=1938) | 0.80 (0.77 to 0.84) | 1.01 (0.97 to 1.05) | 0.83 (0.80 to 0.87) | 1.05 (1.01 to 1.09) | 0.96 (0.91 to 1.02) | 0.1884 |

Yes (n=2877) | 0.82 (0.79 to 0.84) | 1.08 (1.04 to 1.11) | 0.85 (0.82 to 0.87) | 1.12 (1.09 to 1.15) | 0.96 (0.92 to 1.01) | 0.0843 |

Randomised treatment groups were compared by VKA treatment group using a linear regression model with the logarithm of the month 2 biomarker concentration as dependent variable and the logarithm of baseline biomarker concentration and randomised treatment as independent variables. Model-adjusted estimates are presented as geometric means and treatment group differences as ratios of geometric means.

F1+2, fragment 1+2; sCD40L, soluble CD40 ligand; VKA, vitamin K antagonist; vWF, von Willebrand factor.