Abstract Body: Background:
Enlarged perivascular spaces (PVS), a marker of cerebral small vessel disease (SVD), are considered to increase the risk of stroke. However, there is limited data on the benfits and harms of antithrombotic agents in patients with PVS. We assessed the association of PVS with the risk of hemorrhagic or ischemic events in patients receiving antithrombotic agents.
Methods:
This is an investigator-initiated, 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. All participants underwent baseline multimodal MRI. The MRI scans were centrally evaluated for radiologic indicators related to SVD, including white matter hyperintensities (WMH), cerebral microbleeds (CMBs), lacunes, basal ganglia enlarged-perivascular spaces (BGPVS), cortical superficial siderosis, using a visual scale. The outcomes included major bleeding, intracranial hemorrhage, ischemic events, ischemic stroke, and mortality.
Results:
Of the analyzed 5,250 patients (1,736 women; median age 73 [IQR 66–79] years), antiplatelets and anticoagulants were administered at baseline in 3,948 (75.2%) and 1,565 (29.8%), respectively. During a median 2 (IQR1.8–2.0) years, 278 ischemic events, 197 ischemic strokes, 93 major bleeding, 55 intracranial hemorrhage, and 217 deaths were observed. The distribution of BGPVS was as follows: 0 BGPVS in 475 patients (9.4%), 1-10 BGPVS in 2615 patients (51.6%), and 11+ BGPVS in 1975 patients (39.9%). A higher BGPVS burden was associated with older age, a lower proportion of women, higher rates of hypertension and smoking, lower eGFR values, and a higher prevalence of lacunes, CMBs, and WMH. A higher burden of BGPVS was associated with a higher risk of major bleeding (1–10 BGPVS: adjusted hazard ratio (aHR) 1.49, [95% confidence interval CI 0.76–7.92], 11+ BGPVS: aHR 3.27 [1.09–11.57] versus 0 BGPVS; p_trend = 0.035) and ischemic stroke (1–10 BGPVS: aHR 1.79 [0.90–3.57], 11+ BGPVS: aHR 2.39 [1.19–4.81]; p_trend = 0.014). In contrast, higher BGPVS burden was not significantly associated with an increased risk of ischemic events, intracranial hemorrhage, or mortality.
Conclusions:
A higher burden of BGPVS was associated with an increased risk of ischemic stroke and major bleeding in patients taking antithrombotic medication and might be useful in clinical decision making.