WSO December 2023 – Issue 3 - 1149

Markus
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recurrent stroke risk between the two strategies.6 The
results of two other currently ongoing RCTs (OPTIMAS7
and START8) are eagerly awaited. Further usual information
on this question is provided by a study using realworld
data from Germany by Grosse et al.9 PRODAST
(Prospective Record of the Use of Dabigatran in Patients
with Acute Stroke or TIA) was a prospective, multicenter,
observational, post-authorization safety study which
recruited 10,039 patients at 86 German stroke units between
July 2015 and November 2020.9 Of these, 3312 were
treated with dabigatran or vitamin K antagonists (VKA)
and were included in an analysis looking at the risk of
major hemorrhagic events; ischemic events were also
recorded. Major bleeding event rates per 10,000 treatment
days ranged from 1.9 for late administered dabigatran to
4.9 for VKA. Early (⩽ 7 days) or late (7 days) initiation of
dabigatran was associated with a lower hazard for major
hemorrhages as compared to VKA use. The difference was
most marked for intracranial hemorrhages (ICHs) with an
adjusted hazard ratio (HR) of 0.47 (95% CI = 0.10-2.21) for
early dabigatran use versus VKA use and of 0.09 (95%
CI = 0.00-13.11) for late dabigatran use versus VKA use.
No differences were found between early initiation of dabigatran
versus VKA use for ischemic endpoints. The authors
conclude that early administration of dabigatran appears to
be safer than VKA administered at any time point with
regard to the risk of hemorrhagic complications, and in particular
for ICH.
An increased risk of ICH associated with statins has
been reported, although the clinical importance of this
association remains uncertain. A neuroimaging marker
which has been associated with ICH risk10 as well as clinical
outcome such as impaired cognition11 is cerebral microbleeds
(CMBs). Also in this issue, Moutzouri and colleagues
used a cohort of patients with atrial fibrillation to determine
whether statins were associated with an increased risk in
patients with CMB.12 Of 1693 patients with CMB data at
baseline MRI, 802 (47.4%) were statin users. There was no
association between statin use and new CMB, while at
follow-up, there was no difference in ICH rates between
those using statins 14 (1.2%) and those not on statin
(16 (1.3%)).
Moving to acute ischemic stroke, a concerning outcome is
a large middle cerebral artery infarct with expanding cerebral
edema (CED) which is associated with a 70% mortality
unless treated surgically.13 There is still conflicting evidence
over whether reperfusion is associated with a lower risk for
CED in acute ischemic stroke. Thoren and colleagues, also in
this issue, addressed this question in 4640 patients with occlusion
of the intracranial internal carotid or middle cerebral
artery (M1 or M2) who had undergone thrombectomy, from
the Safe Implementation of Treatment in Stroke (SITS)-
International Stroke Thrombectomy Registry.13 Moderate
or severe CED was less frequent among patients who had
reperfusion compared to patients without reperfusion: 12.5%
versus 29.6% (p < 0.05) and adjusted relative risk (RR) = 0.50
(95% CI = 0.44-0.57). They conclude that in patients with
large artery anterior circulation occlusion stroke who undergo
thrombectomy, successful reperfusion is associated with an
approximately 50% lower risk of early CED. A further paper
also in this issue from the Italian Registry of Endovascular
Treatment in Acute Stroke determined predictors of CED in
1400 patients.14 Higher National Institutes of Health Stroke
Scale (NIHSS), lower Alberta Stroke Program Early CT score
(ASPECTS), longer onset-to-groin time, longer procedure
time, and poor collaterals were all predictors for early CED.
Finally, there have been numerous examples where the
primary endpoint of a clinical trial is negative, but secondary
analyses suggest a possible benefit in a particular subgroup.
This sometimes persuades the company or
researchers to undertake another trial in the subgroup; in
my experience, these second trials are often negative. This
emphasizes the rigor and caution required in performing
secondary analyses. This makes the article by Ademola and
colleagues in this issue relevant and rather concerning.15
They carried out a systematic review on the credibility of
subgroup analyses in stroke trials. 64% of all secondary
analyses were assessed to have low credibility. They conclude
the quality of subgroup analysis reporting in stroke
trials remains poor. More effort is needed to train trialists
on the best methods for designing and performing subgroup
analyses and how to report the results.
Hugh S Markus
University of Cambridge, Cambridge, UK
Email: hsm32@medschl.cam.ac.uk
References
1. Singhal AB. Reversible cerebral vasoconstriction syndrome:
a review of pathogenesis, clinical presentation, and treatment.
Int J Stroke. 2023; 18: 1151-1160.
2. Markus HS, Levi C, King A, Madigan J and Norris J; Cervical
Artery Dissection in Stroke Study (CADISS) Investigators.
Antiplatelet therapy vs anticoagulation therapy in cervical
artery dissection: the Cervical Artery Dissection in Stroke
Study (CADISS) randomized clinical trial final results. JAMA
Neurol 2019; 76: 657-664.
3. Mayer-Suess L, Dejakum B, Ratzinger G, Gizewski ER,
Kiechl S and Knoflach M. Clinical characteristics and outcome
in expansive compared with steno-occlusive mural
hematoma in spontaneous cervical artery dissection. Int J
Stroke. 2023; 18: 1186-1192.
4. Lounsbury E, Niznick N, Mallick R, et al. Recurrence of cervical
artery dissection: a systematic review and meta-analysis.
Int J Stroke. Epub ahead of print 21 September 2023. DOI:
10.1177/17474930231201434.
5. Oldgren J, Åsberg S, Hijazi Z, et al. Early versus delayed
non-vitamin K antagonist oral anticoagulant therapy after
acute ischemic stroke in atrial fibrillation (TIMING): 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
