Efficacy and Safety of Direct Oral Anticoagulant for Treatment of Atrial Fibrillation in Cerebral Amyloid Angiopathy

Abstract

A 75-year-old man with a history of atrial fibrillation (AF) and anticoagulant therapy presented with a headache. Cerebral amyloid angiopathy (CAA) was diagnosed after MRI of the brain revealed cortical superficial siderosis, lobar intracerebral hemorrhage, and lobar microbleeds. Anticoagulant therapy was carefully discontinued. Several years later, he was admitted with sudden onset left upper-extremity weakness. In addition to CAA bleeding lesions, a diffusion-weighted brain MRI showed multiple infarct lesions of high signal intensity. The administration of edoxaban 7.5 mg/day (later increased up to 30 mg/day) prevented ischemic stroke recurrence without exacerbation of cerebral bleeding. This could indicate that CAA patients with AF who had previous adverse effects from warfarin can safely use newer direct oral anticoagulants, such as edoxaban, to prevent ischemic stroke without danger of cerebral hemorrhage. The superiority of edoxaban as compared with warfarin might be due to its antioxidant effect because vascular oxidative stress plays a causal role in CAA-induced cerebrovascular dysfunction, CAA-induced cerebral hemorrhage, and CAA formation itself. We explained the beneficial effect of edoxaban for CAA by the mechanism of oxidative stress in the paper.

Keywords: anticoagulant therapy; atrial fibrillation; cerebral amyloid angiopathy; direct oral anticoagulant; oxidative stress.

Figure 1. Summary of the progress of this case

A: T1-weighted image (T1WI) sequence showing a hypodensity lesion in the right putamen. B: Axial fluid-attenuated inversion recovery (FLAIR) sequences showing an isodensity with 7 mm at the same lesion with A, which suggested old cerebral bleeding. C: T2WI sequence showing hemosiderosis in the left frontal lobe. D: T2*WI sequence showing a low-intensity lesion in the left frontal lobe. E: T1WI sequence showing high intensities in the same lesion as D, in the left frontal lobe, which suggests subacute cerebral hemorrhage. F: Cerebral CT showing left cerebellar infarction. G, H: Diffusion-weighted image (DWI) sequence showing multiple deep and cortical infarct lesions, including right central groove lesion. I: DWI sequence showing recurrence of cerebral infarction in other sites. J: Time course of the level of D-dimer and medical treatment about anticoagulation.