Abstract Body: Objectives
Cortical superficial siderosis (cSS) has been implicated as a putative hemorrhagic MRI finding of cerebral small vessel disease (SVD) related to cerebral amyloid angiopathy. Few reports have examined the association between cSS and antithrombotic-related clinical events. The aim of this study is to investigate the association of cSS with the risk of hemorrhagic or ischemic events in patients receiving antithrombotic agents.

Methods
This is a prospective, multicenter, observational study that enrolled patients with cerebrovascular or cardiovascular diseases who were taking oral antithrombotic agents from 52 hospitals across Japan between 2016 and 2019. The MRI scans were centrally evaluated for SVD, including white matter hyperintensities (WMH), cerebral microbleeds (CMBs), lacunes, basal ganglia-enlarged perivascular spaces (BGPVS), cortical superficial siderosis (cSS), using a visual scale. The outcomes included subsequent ischemic events (ischemic vascular events [IVE], ischemic stroke [IS]), hemorrhagic events (major bleeding [MB], intracranial hemorrhage [ICH], non-major bleeding[nMB]), and mortality. We calculated incidence rates (IR) per 1,000 patient-years of each event and the IR ratio (IRR).

Results
Of 5037 patients (mean age 71.2 ± 11.2 years, 67% men), cSS was detected in 105 (2.0%) patients. The cSS group was older and had a higher proportion of males, atrial fibrillation, histories of intracerebral hemorrhage or subarachnoid hemorrhage and a higher frequency of strictly lobar CMBs, WMH, and lacunes compared to the non-cSS group. During a median 2 [IQR1.8–2.03] years, 278 IVE, 197 IS, 93 MB, 55 ICH, 147 nMB, and 217 deaths were observed. In the cSS group, IVE and IS were numerically less frequent (IVE: IR 20.95 vs 29.13; IS: 15.64 vs 20.34, per 1000 patient-years), while MB and mortality (MB: IR 9.61 vs 5.15; mortality: IR 35.82 vs 21.87) were numerically more frequent, compared to the non-cSS group, but the IRR of each event did not significantly differ between the 2 groups. In the cSS group on warfarin (n=12), there was a trend towards numerically higher rates of MB (IR 80.36 vs 18.54), ICH (IR 80.36 vs 15.84), and mortality (IR 142.95 vs 39.61, per 1000 patient-years) compared to the non-cSS group.

Conclusion
Individuals with cSS receiving antithrombotic agents exhibited a higher trend for mortality and major bleeding.