WSO - April 2024 - 376

1237297
WSO
International Journal of StrokeEditorial
Editorial
Treating inflammation to reduce stroke
risk, non-motor symptoms after stroke,
cerebral microinfarcts in cancer, and
prognosis in cervical dissection
Increasing evidence is implicating chronic inflammation in
the pathogenesis of stroke and in the risk of recurrent
ischemic events after a stroke or transient ischemic attack
(TIA). This has raised the exciting question as to whether
drugs which inhibit inflammation could reduce stroke risk.
However, the field is complex; for example, inflammation
may well play a different role in different pathogenic subtypes
of stroke. An excellent review by Zietz and colleagues
in this issue of the International Journal of Stroke (IJS)
updates us on the field.1 They first discuss the role inflammatory
pathways play in the etiology of ischemic stroke
and its different subtypes; they then review the evidence
that peripheral inflammatory markers predict recurrent
events after stroke, and finally, they update us on trials of
anti-inflammatory agents for vascular prevention.
Considerable experimental work, genetic epidemiological
data, and plaque imaging studies all implicate inflammation
in atherosclerotic stroke, and atherosclerosis is
considered an " inflammatory " disease by many. This has
led to the hypothesis that anti-inflammatory drugs could
reduce atherosclerosis-related consequences like coronary
artery disease and large artery stroke. However, emerging
evidence suggests that inflammatory mechanisms may also
play a role in other subtypes of stroke, for example, cerebral
small vessel disease where they may be related to
blood-brain barrier dysfunction.2
Recent studies have demonstrated that modulating
inflammation can reduce cardiovascular risk.
The
CANTOS (Canakinumab Anti-Inflammatory Thrombosis
Outcome Study) trial tested the efficacy of canakinumab,
a human monoclonal antibody to interleukin (IL)-1β, in
participants with a history of myocardial infarction and a
high sensitivity C-reactive protein (hsCRP) of >2 mg/L
despite aggressive secondary prevention.3 Canakinumab
reduced the risk of recurrent cardiovascular events and
death but it was also associated with a higher risk of death
due to infection, neutropenia, and thrombocytopenia. The
CANTOS trial was pivotal in that it demonstrated proof of
principle that targeting the IL-6-CRP (C-reactive protein)
axis can reduce recurrent events in patients with established
atherosclerosis.
An alternative anti-inflammatory approach is colchicine,
which inhibits microtubule and inflammasome assembly,
reduces cytokine/adhesion molecule expression, and
reduces inflammatory cell mitosis and motility. A number
International Journal of Stroke, 19(4)
International Journal of Stroke
2024, Vol. 19(4) 376 -378
© 2024 World Stroke Organization
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DOI: 10.1177/17474930241237297
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https://doi.org/10.1177/17474930241237297
of randomized controlled trials, described in the review,1
have demonstrated that colchicine is associated with a
reduced risk of recurrent cardiovascular events in patients
after myocardial infarction, and it was approved as a treatment
for cardiovascular disease by the US Food and Drug
Administration (FDA) in June 2023. Advantages of colchicine
include low cost, wide availability globally including
in low- and middle-income countries, good tolerability, and
an established safety profile at low doses.1 However, it is
contraindicated in patients with severe chronic kidney disease.
Interestingly, the cardiac trials showed an almost
halving of stroke risk.4 Colchicine is now being evaluated
in patients with stroke.
The Colchicine in High-risk Patients with Acute Minorto-moderate
Ischemic Stroke or Transient Ischemic Attack
(CHANCE-3) randomized, double-blind, placebo-controlled
multicentre trial randomized 8238 patients with
acute minor-to-moderate ischemic stroke (NIHSS ⩽ 5) or
high-risk TIA and a hsCRP level of ⩾2 mg/L within 24 h of
symptom onset to colchicine or placebo for 90 days.5
Results were presented at the World Stroke Congress in
October 20236 and showed no protective effect. However,
if colchicine is protective via a long-term anti-inflammatory
effect on atherosclerosis, one might expect benefit to
require long-term treatment. The Colchicine for prevention
of vascular inflammation in Non-CardioEmbolic
stroke (CONVINCE) trial7 is looking at long-term secondary
prevention and has enrolled 3154 non-cardioembolic
strokes; results are eagerly awaited and should be available
in 2024.
Globally, stroke is the second most common cause of
death and the third leading cause of disability-adjusted life
years.8 Outcome measurement in stroke is dominated by
motor impairments, communication, and mobility, often
assessed using the modified Rankin scale, which does not
fully capture the impact of key non-motor outcome
domains. Such impairments include post-stroke anxiety,9
depression,10 apathy,11 and fatigue12 and are associated with
functional disability and premature death. They have been
highlighted in multiple surveys as being disabling for
patients and having a major impact on quality of life.13
Despite this, they have been relatively neglected in the
stroke research field. This makes the article by Ozkan and
colleague in this month's issue of IJS very topical and
important.14 They followed up 605 patients with stroke
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WSO - April 2024

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