Does statin increase the risk of intracerebral hemorrhage in stroke survivors? A meta-analysis and trial sequential analysis

Your responsible doctor will have to do the analysis  on benefits of statins vs. risks since our fucking failures of stroke associations won't do a damn thing and write up a protocol on use.  

Statins.
tested in rats from 2003
http://oc1dean.blogspot.com/2011/09/statins-induce-angiogenesis.html 
http://oc1dean.blogspot.com/2013/02/simvastatin-attenuates-stroke-induced.html
Or,
Simvastatin attenuates axonal injury after experimental traumatic brain injury and promotes neurite outgrowth of primary cortical neurons
tested in humans, March, 2011
http://www.medwirenews.com/39/91658/Stroke/Acute_statin_therapy_improves_survival_after_ischemic_stroke.html

 

Does statin increase the risk of intracerebral hemorrhage in stroke survivors? A meta-analysis and trial sequential analysis 

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Ru Jian Jonathan Teoh, Chi-Jung Huang, Chi Peng Chan, ...

First Published July 24, 2019 Research Article

https://doi.org/10.1177/1756286419864830

Article information

Abstract

Background:

It remains debatable whether statin increases the risk of intracerebral hemorrhage (ICH) in poststroke patients.

Methods:

We systematically searched PubMed, EMBASE, and CENTRAL for randomized controlled trials. Trial sequential analysis (TSA) was conducted to assess the reliability and conclusiveness of the available evidence in the meta-analysis. To evaluate the overall effectiveness, the net composite endpoints were derived by totaling ischemic stroke, hemorrhagic stroke, transient ischemic attack (TIA), myocardial infarction, and cardiovascular mortality.

Results:

A total of 17 trials with 11,576 subjects with previous ischemic stroke, TIA, or ICH were included, in which statin therapy increased the risk of hemorrhagic stroke (risk ratio [RR], 1.42; 95% confidence interval [CI], 1.07–1.87), but reduced the risk of ischemic stroke (RR, 0.85; 95% CI, 0.75–0.95). For the net composite endpoints, statin therapy was associated with a 17% risk reduction (95% CI, 12–21%; number needed to treat = 6). With a control event rate 2% and RR increase 40%, the TSA suggested a conclusive signal of an increased risk of hemorrhagic stroke in stroke survivors taking statin. However, with the sensitivity analysis by changing assumptions, the conclusions about hemorrhagic stroke risk were less robust.

Conclusions:

Statin therapy in poststroke patients increased the risk of hemorrhagic stroke but effectively reduced ischemic stroke risk. Weighing the benefits and potential harms, statin has an overall beneficial effect in patients with previous stroke or TIA. However, more studies are required(Wow, way to take no responsibility of your work.) to investigate the conclusiveness of the increased hemorrhagic stroke risk revealed in our study.

Keywords cardiovascular events, cerebrovascular disease, meta-analysis, secondary stroke prevention, statin, trial sequential analysis

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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