WSO October 2023 – Issue 1 - 989

Shiozawa et al.
989
Figure 2. Kaplan-Meier curves for endpoints in the total population and by anticoagulant medication (warfarin, DOACs, and
no-OAC groups). (a) Ischemic stroke. (b) ICH. (c) Intracerebral hemorrhage. (d) Subarachnoid hemorrhage. (e) Subdural/epidural
hemorrhage.
(a)
(b)
(c)
(d)
(e)
Ischemic stroke as an endpoint
Baseline characteristics of the 743 patients developing
ischemic stroke are shown in Supplemental Table 1.
Patients who developed ischemic stroke were older; had
higher diastolic blood pressure, lower creatinine clearance,
and higher scores of CHADS2, CHA2DS2-VASc, and HASBLED;
more commonly had persistent/permanent AF as
AF types, diabetes mellitus, heart failure, dementia, and
histories of cerebrovascular disease, thromboembolic disease,
major bleeding, and fall; less commonly received
catheter ablation for AF; more commonly took warfarin;
and less commonly took DOACs than patients who did not
develop ischemic stroke.
The incidence of ischemic stroke was significantly different
among the three groups (warfarin, DOACs, and noOAC
groups; log-rank p < 0.001, Kaplan-Meier analysis,
Figure 2(a); note that 12 patients receiving parenteral anticoagulants
were excluded from the analysis). Compared
with warfarin use, DOAC use was inversely associated
(adjusted HR (aHR) 0.82, 95% CI 0.70-0.97) and no-OAC
use was positively associated (aHR 1.62, 95% CI 1.24-
2.13) with ischemic stroke (Table 1). On propensity score
matching, DOAC use was inversely associated with
ischemic stroke relative to warfarin use (aHR 0.79, 95% CI
0.65-0.97).
Supplemental Table 2 and Figure 3 show the association
of baseline characteristics with ischemic stroke. Older age,
higher systolic blood pressure, lower creatinine clearance,
persistent/permanent AF, diabetes mellitus with higher glycated
hemoglobin A1c level, prior cerebrovascular disease,
thromboembolic disease, fall, and no anticoagulation (vs
warfarin) were positively associated with ischemic stroke,
and prior catheter ablation, DOAC (vs warfarin), and antiplatelet
use were inversely associated with ischemic stroke.
Of the 743 patients who developed ischemic stroke, 100
(0.17/100 person-years, 95% CI 0.13-0.20) were fatal
cases. Causes of death were nervous system disorders for
89 patients (all died from the index stroke or stroke recurrence);
cardiac disorders, 4 (3 heart failure and 1 hypertrophic
cardiomyopathy); infections, 4 (3 pneumonia and 1
sepsis); and others, 3. Supplementalry Table 2 and Figure 3
show the association of baseline characteristics with fatal
ischemic stroke; older age, persistent and permanent AF,
prior cerebrovascular disease, and thromboembolic disease
were positively associated.
Of the 743 patients with ischemic stroke, 483 (0.80/
100 person-years, 95% CI 0.73-0.88) were not directly discharged
home. DOAC use was inversely associated and noOAC
use was positively associated with ischemic stroke
without home discharge (Table 1).
Similar results were seen when 3883 patients taking offlabel
doses of DOACs were excluded (Supplemental Table 3).
ICH as an endpoint
Baseline characteristics of the 453 patients with ICH are
shown in Supplemental Table 1. Patients who developed
ICH were older; had lower body mass index, lower creatinine
clearance, and higher scores of CHADS2, CHA2DS2VASc,
and HAS-BLED; more commonly had severe
hepatic disease, dementia, and histories of cerebrovascular
International Journal of Stroke, 18(8)
WSO October 2023 – Issue 1

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