WSO December 2023 – Issue 3 - 1175

Grosse et al.
1175
Figure 2. Case numbers and hazard ratio estimates (with 95% confidence intervals) for current use of dabigatran compared
to current use of VKA. Highlighted estimates are from adjusted models. (a) Hemorrhagic endpoints, death, and composite
endpoint; and (b) ischemic endpoints. CI: confidence interval; EP: endpoint; HR: hazard ratio; ICH: intracranial hemorrhage; TIA:
transient ischemic attack; VKA: vitamin K antagonists.
Ischemic Stroke With Atrial Fibrillation (TIMING) study
was the first RCT on this topic and showed that early initiation
of anticoagulation was noninferior to delayed initiation
concerning a composite endpoint of ischemic stroke, death,
and ICH.2 The results of other currently ongoing RCTs, that
is, ELAN,5 OPTIMAS,4 and START,3 are eagerly awaited.
Real-world evidence reflecting the initiation or resumption
of anticoagulants in daily practice is crucial as a complement
to data derived from RCTs. Precisely, in this study, we
were interested in whether an early start of dabigatran after
AIS or TIA is safer than use of VKA.
PRODAST is the largest prospective study, which is
dedicated to the issue of anticoagulation in the early phase
following AIS or TIA in patients with AF. In this analysis
focusing on the initiation of dabigatran in comparison to
VKA, we were able to investigate data from in total 3312
patients for whom detailed characteristics and follow-up
data for up to 3 months were prospectively collected.
Our data show that, in general, the rates of recurrent vascular
events were very low following initiation of anticoagulants.
Compared to previous observational studies
which were conducted in the pre-NOAC era,1,11 the rates of
outcome events in PRODAST are substantially lower,
which must be interpreted as a recent improvement of secondary
stroke prevention in routine clinical practice.
In the Randomized Evaluation of Long
Term
Anticoagulant Therapy With Dabigatran etexilate (RE-LY)
trial that led to the approval of dabigatran for secondary
stroke prevention, dabigatran was at least as effective in
preventing AIS and safer in regard to hemorrhagic complications
compared to warfarin.17 Our analysis now provides
evidence that this observation holds true also in the early
phase following AIS and TIA in a real-world setting. This is
in accordance with findings from a pooled analysis of different
observational studies.23 One shortcoming of observational
studies is confounding by indication. This becomes
apparent in the patient characteristics, which show that
physicians favored later use of dabigatran in patients with
more severe strokes. Patients who were treated with thrombolysis
or mechanical thrombectomy, and those who
already had HT shown by initial imaging, were more likely
to receive anticoagulation later. To account for the complex
causal structures behind this decision-making, we applied
DAGs in detail to identify appropriate adjustment sets to
estimate the total effect of the use of anticoagulation on the
endpoints.
When comparing early or late initiation of dabigatran
with VKA use, the rates for major hemorrhagic events were
substantially lower in dabigatran-treated patients after
adjustment for confounders. The rate for ICH was reduced
by 54%, and 91% when comparing early or late dabigatran
initiation with VKA use, respectively. The observation that
delayed initiation with dabigatran may be associated with
higher rates of ischemic stroke is consistent with clinical
experience and existing evidence from previous observational
studies.1
Considering outcome events occurring under the current
treatments, we observed similar results: compared with
VKA, current use of dabigatran reduced the rate of major
hemorrhages, in particular ICH, myocardial infarction, and
death. Ischemic strokes, however, were not prevented by
current dabigatran treatment compared with VKA
treatment.
The clear strength of our study is the multicenter, prospective
design, which accurately represents the real-world
administration of anticoagulants after AIS and TIA in a
International Journal of Stroke, 18(10)

WSO December 2023 – Issue 3

Table of Contents for the Digital Edition of WSO December 2023 – Issue 3