Table.

Secondary outcomes of trial.

A. Efficacy

1. Neuroradiological markers i) Rates of change in mean diffusivity (assessed on MR imaging) ii) Rates of change in mean fractional anisotropy (as a measure of microstructural white matter damage derived from diffusion tensor imaging) iii) Rates of change on T1-weighted volumetric images of total brain volume iv) Rates of changes on T1-weighted volumetric images of white matter hyperintensities v) Rates of change on T1-weighted volumetric images of grey matter volume vi) Total number of brain infarcts per person as well as the number of these events overall vii) Number of subcortical brain infarcts per person as well as the number of these events overall viii) Number of cortical brain infarcts per person as well as the number of these events overall

2. Clinical i) Vascular events a) Number of ischemic stroke or transient ischemic attacks per person as well as the number of these events overall b) Number of occlusive arterial events at other sites, including systemic embolism per person, as well as the number of these events overall c) Number of cerebral venous thrombosis per person as well as the number of these events overall d) Number of venous thromboemboli at other sites per person as well as the number of these events overall e) Number of microvascular thrombosis per person as well as the number of these events overall f) Number of superficial venous thrombosis per person as well as the number of these events overall ii) Death iii) Composite clinical outcomes a) The number of the composite of all thrombotic events: arterial, venous, microvascular, and death per person, as well as the number of these events overall b) The number of Major Adverse Cardiac and Cerebrovascular events per person, as well as the number of these events overall iv) Rate of change in cognitive function assessed by the Montreal Cognitive Assessment in conjunction with the Queen Square Cognitive Assessment score

B. Safety

1.Bleeding: The number of all bleeding events: major, clinically relevant nonmajor, minor per person, as well as the number of these events overall 2.The Number of serious adverse events other than major bleeding per person as well as the number of these events overall 3.The number of cerebral microbleeds assessed with susceptibility-weighted imaging as a surrogate marker of bleeding risk per person as well as the number of these events overall

C. Health economics

1.Quality of life assessed using 5-level EQ-5D-5L 2.Health and social care resource use assessed using trial follow-up visit case report forms 3.Mean incremental cost per quality-adjusted life year

D. Anticoagulation intensity

1. Rivaroxaban i) Rivaroxaban concentration measured with an amidolytic anti-Xa assay

2. Warfarin i) Time in target INR therapeutic range ii) Factor X level measured with an amidolytic factor X assay (LA independent assessment of warfarin anticoagulant effect)

E. Exploratory outcomes

1.Rivaroxaban pharmacokinetic modeling 2.Cerebral blood flow derived from MR perfusion imaging using an arterial spin labeling technique

INR, international normalized ratio; LA, lupus anticoagulant; MR, magnetic resonance.