Introduction
Statins can reduce cardiovascular events and mortality among patients with coronary heart disease.
1,2
However, in patients with acute or previous history of ischemic stroke
and intracerebral hemorrhage (ICH), findings on the use of statins are
inconsistent. In a meta-analysis with more than 100,000 patients, statin
use in patients with acute stroke was found to be associated with good
functional outcomes at 3 months but not at 1 year.
3
A few other meta-analyses also found that statins have no significant
benefits in patients with acute stroke in reducing recurrent ischemic
stroke or ICH, cardiovascular events, and mortality.
4,5
Some studies found an inverse relationship between low-density
lipoprotein cholesterol (LDL-C) and the risk of ICH, and some found a
risk of hemorrhagic transformation in patients using statins.
6–11
However, the Stroke Prevention by Aggressive Reduction in Cholesterol
Levels (SPARCL) study found a significant risk of ICH associated with
statin use in poststroke patients.
6
A meta-analysis of four studies in 2008 investigating statin therapy in
patients with cerebrovascular diseases suggested that statins reduced
risk of overall and ischemic stroke but increased risk of hemorrhagic
stroke.
12
However, results of many new studies for stroke survivors were reported
after 2008, which provided more information about the effects of
statins in poststroke patients.
13–16
Systematic
review and meta-analyses of existing randomized controlled trials
(RCTs) can help to summarize the totality of current existing evidence
and clarify the conflicting information on the benefits and risks of
statin therapy in poststroke patients. However, meta-analysis may result
in random errors due to sparse data and repeated significance testing
when updating a meta-analysis with new trials. Therefore, trial
sequential analysis (TSA) has been developed to reduce the spurious
inference from meta-analysis.
17
Consequently, we performed an updated systematic review with
meta-analysis and TSA of published RCTs to investigate the effect of
statin therapy on stroke recurrence (including ischemic stroke and ICH),
major adverse cardiovascular events (MACEs), and cardiovascular
mortality, and also to evaluate its overall effectiveness in patients
with previous ischemic stroke or ICH.
Methods
The
prespecified protocol for this review was registered with the
International Prospective Register of Systematic Reviews (PROSPERO),
number CRD 42017079212, and the study report adhered to the Preferred
Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)
guideline (
Table S1).
18 All analyses were based on previously published studies, thus no ethical approval and patient consent was required.
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