Balali_Pargol_MSc thesis_Neuroscience department_2023Sep / Background: Cerebral microbleeds are asymptomatic neuroimaging markers of small
vessel disease (SVD), visualized as small hypointensities on blood-sensitive magnetic
resonance imaging (MRI) sequences. Patients with ischemic stroke and microbleeds are
at a higher risk of future ischemic stroke and intracranial hemorrhage. Antithrombotic
therapies, the mainstay treatment of secondary stroke prevention, are associated with an
increased risk of bleeding. This raises concerns surrounding the net benefit of
antithrombotic therapies in these hemorrhage-prone patients. The overarching aim of this
thesis is to determine the safety of antithrombotic treatments in patients with hemorrhage-prone SVD marked by microbleeds on MRI or prior intracerebral hemorrhage (ICH). I
aimed to characterize the association between baseline microbleeds and the risk of future
clinical outcomes in patients with ischemic stroke and whether there exists treatment
effect modification of different anticoagulants on clinical outcomes according to
microbleeds presence, location, and number.
Methods: We performed post hoc analyses on two multicenter previously conducted
randomized trials in patients with non-cardioembolic ischemic stroke. For the PACIFIC-STROKE trial, we used multivariable regression models to determine the contribution of
microbleeds to the risk of new microbleeds, hemorrhagic transformation (HT), ischemic
stroke, intracranial hemorrhage, and death. We assessed the treatment effect of
asundexian, a factor XIa inhibitor, vs. placebo on these clinical outcomes, stratified by
microbleeds presence, location, and number.
I was trained on standardized rating of microbleeds on MRI, achieved excellent interrater
reliability, and rated all DATAS-II participant MRIs. I used multivariable logistic
regression models to identify the association between microbleeds and HT and 90-day
excellent functional outcome. I assessed the interaction between treatment with
dabigatran, a direct thrombin inhibitor, vs. aspirin and microbleeds for these outcomes.
Separately, I performed a review of the literature and wrote an editorial discussing the
optimum timing of antiplatelet re-initiation after ICH.
Results: The PACIFIC-STROKE post hoc analyses showed that microbleeds are
associated with a 1.6-fold and 4.4-fold higher risk of HT and new microbleeds,
respectively. The DATAS-II exploratory analyses demonstrated no association between
the risk of outcomes and microbleeds presence. We found no interaction between
treatment assignment and microbleed presence for any of the clinical outcomes
investigated in either of these studies. Based on the totality of evidence, we concluded
that early resumption of antiplatelets in ICH survivors is likely to be safe.
Conclusion: Our findings do not support existing concerns surrounding the use of
anticoagulants in patients with acute ischemic stroke and microbleeds on MRI, nor for the
early resumption of antiplatelets in ICH survivors. / Thesis / Master of Science (MSc) / Diseases of small brain blood vessels can lead to strokes due to blockage or
bleeding. Small, asymptomatic brain bleeds on MRIs (microbleeds) are common among
affected patients. Patients with clot-induced stroke and microbleeds have a higher risk of
both types of strokes. Blood thinners are standard treatments to prevent future clotting
events after clot-induced stroke. However, their potential to increase the risk of brain
bleeding has raised concerns regarding their use in patients with microbleeds or bleeding-induced stroke.
We assessed information from two large, previously completed randomized trials
to evaluate the safety of strong blood thinners (anticoagulants) in patients with clot-induced
stroke and microbleeds. Additionally, we evaluated the risk vs. benefit of
restarting milder blood thinners (antiplatelets) early after bleeding-induced stroke.
Bleeding was more prevalent in patients with microbleeds; however, the effect of
the anticoagulants tested on bleeding outcomes was not modified by microbleed
presence. Overall, our findings suggest that blood thinners are safe in patients with clot-induced stroke and microbleeds, and that early resumption of antiplatelets seems safe in
patients with bleeding-induced stroke.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29010 |
| Date | January 2023 |
| Creators | Balali, Pargol |
| Contributors | Shoamanesh, Ashkan, Neuroscience |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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