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Curr Vasc Pharmacol. 2013 Nov;11(6):812-6.
Risk and benefit of statins in stroke secondary prevention.
Laloux P1.
Abstract
Statin is now recommended in secondary prevention after stroke or transient ischemic attacks to reduce the risk of a new stroke or major cardiovascular events. However, some issues about the extent of the benefit in some stroke patients and the risk of cerebral hemorrhage remain debated. This review shows that statins are significantly effective in decreasing the risk of further strokes despite an increase in the risk of brain hemorrhage. A significant benefit was observed in men and women, in aged patients and possibly to a greater extent in patients with carotid artery stenosis. Intensive statin therapy lowering the LDL-cholesterol beyond the cut-off value of 1.8 mmol/L (70 mg/dl) seems to be more effective than less intensive treatment and without an increased risk of side effects. Overall, statins are well tolerated. Further prospective studies should clarify whether the effect is of the same magnitude in small vessel disease and how to select the patients to reduce the risk of cerebral hemorrhage.
PMID:
24484462
[Indexed for MEDLINE]
BMJ Open. 2015 Feb 25;5(2):e007075. doi: 10.1136/bmjopen-2014-007075.
Statin use and risk of haemorrhagic stroke in a community-based cohort of postmenopausal women: an observational study from the Women's Health Initiative.
Salmoirago-Blotcher E1, Hovey KM2, Andrews CA2, Robinson JG3, Johnson KC4, Wassertheil-Smoller S5, Crawford S6, Qi L7, Martin LW8, Ockene J9, Manson JE10.
Abstract
OBJECTIVES:
To determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment.
DESIGN:
Observational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials.
SETTING:
Women were recruited from 40 participating sites.
PARTICIPANTS:
Cohort of 68,132 women followed through 2005 (parent study) and for an additional 5 years in the extension study.
MAIN OUTCOME MEASURES:
Statin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in original containers for inventory. Strokes were ascertained semiannually and centrally adjudicated. Risk of HS by statin use (time-varying covariate, with the 'no use' category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for HS (model 2); and possible confounders by indication (model 3). Prespecified subgroup analyses were conducted by use of antiplatelet medications.
RESULTS:
Final models included 67,882 women (mean age, 63±7 years). Over a mean follow-up of 12 years, incidence rates of HS were 6.4/10,000 person-years among statin users and 5.0/10,000 person-years among non-users (p=0.11). The unadjusted risk of HS in statinusers was 1.21 (CI 0.96 to 1.53); after adjusting for age and HS risk factors the HR was 0.98 (CI 0.76 to 1.26). Risk of HS was higher among women on statins and antiplatelet agents versus women on antiplatelet medications alone (HR=1.59; CI 1.03 to 2.47); p for interaction=0.011.
CONCLUSIONS:
This retrospective analysis did not show an association between statin use and HS risk among older women. HS risk was higher among women taking statins with antiplatelet agents. These findings warrant further investigation, given potential implications for clinical decision-making.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
KEYWORDS:
PREVENTIVE MEDICINE
PMID:
25716175
PMCID:
DOI:
[Indexed for MEDLINE]
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J Stroke Cerebrovasc Dis. 2013 Jan;22(1):66-71. doi: 10.1016/j.jstrokecerebrovasdis.2011.06.008. Epub 2011 Jul 22.
Early statin use is associated with increased risk of infection after stroke.
Becker K1, Tanzi P, Kalil A, Shibata D, Cain K.
Abstract
BACKGROUND:
Infection after stroke is common and likely detrimental. Given the potent immunomodulatory properties of statins, we hypothesized that early statin use might increase the risk of infection in the immediate post stroke period.
METHODS:
In a study cohort of 112 patients with ischemic stroke, we assessed the impact of early statin use on the risk of post strokeinfection.
RESULTS:
After controlling for stroke severity and patient age, the odds ratio (OR) and 95% confidence interval (CI) for infection in the first 15 days after stroke among patients on a statin by day 3 after stroke was 7.21 (95% CI 1.40-37.98; P = .018). When controlling for univariate predictors of infection, the OR associated for infection associated with statin use actually increased, but was no longer significant (8.49 [95% CI 0.92-77.98]; P = .059). In addition, early statin use was associated with an increase in plasma interleukin-1 receptor antagonist (IL-1ra); IL-1ra was significantly higher in early statin users than in nonstatin users by day 7 after stroke.
CONCLUSIONS:
Our data suggest that early statin use appears to be associated with and increased risk of post stroke infection. This riskmay, in part, be related to increases in plasma IL-1ra. If these findings are replicated in larger studies, they could have important implications for the timing of statin therapy after stroke.
Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.
PMID:
21782466
PMCID:
DOI:
10.1016/j.jstrokecerebrovasdis.2011.06.008
[Indexed for MEDLINE]
J Neurol Sci. 2015 Jan 15;348(1-2):89-93. doi: 10.1016/j.jns.2014.11.013. Epub 2014 Nov 18.
Statin use increases the risk of depressive disorder in stroke patients: a population-based study.
Kang JH1, Kao LT2, Lin HC3, Tsai MC4, Chung SD5.
Abstract
This study aimed to explore the risk for depressive disorder (DD) among stroke patients with statin use. Totally, 11,218 patients who had a first-time acute hospitalization for stroke were identified from Taiwan's Longitudinal Health Insurance Database 2000. We individually followed each study subject for a 1-year period to identify those patients who were subsequently diagnosed with DD during the follow-up period. We found that the incidence rate of DD during the 1-year follow-up period was 5.52 (95% CI: 4.70-6.43) and 3.46 (95% CI: 3.08-3.88) per 100 person-years for stroke patients who were statin users and nonusers, respectively. Cox proportional hazards regressions revealed that the adjusted hazard ratio (HR) for DD during the 1-year follow-up period was 1.59 for stroke patients who were statin users compared to those who were non-statin users. We further found that the adjusted HR for DD for stroke patients who were regular statin users was 1.65 compared to stroke patients who had never been prescribed statin. However, there was no increased hazard of DD for stroke patients who were irregular statin users compared to stroke patients who had never been prescribed statin (HR: 1.22, 95% CI: 0.70-2.11).
Copyright © 2014. Published by Elsevier B.V.
KEYWORDS:
Cerebrovascular disease; Depression; Depressive disorder; Epidemiology; Statin; Stroke
Comment in
- Letter by Huang regarding the article, "Statin use increases the risk of depressive disorder in stroke patients: A population-based study". [J Neurol Sci. 2015]
PMID:
25483831
DOI:
Stroke. 2014 May;45(5):1492-4. doi: 10.1161/STROKEAHA.114.004130. Epub 2014 Apr 8.
Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study.
Romero JR1, Preis SR, Beiser A, DeCarli C, Viswanathan A, Martinez-Ramirez S, Kase CS, Wolf PA, Seshadri S.
Abstract
BACKGROUND AND PURPOSE:
Cerebral microbleeds (CMBs) are associated with increased risk of stroke and poor cognition. Vascular riskfactors and medications used for stroke prevention may increase the risk of CMB. We examined the prevalence of CMB and the association of these risk factors with CMB, postulating that risk factors for cerebral amyloid angiopathy would be associated with lobar CMB and markers of hypertensive vasculopathy with deep CMB.
METHODS:
We include 1965 Framingham Original and Offspring participants (age, 66.5±11.0 years; 54% women) and evaluated the age- and sex-specific prevalence of CMB. We related various vascular and genetic (apolipoprotein E [APOE]) risk factors and medication use to the presence of CMB overall and stratified by brain location (deep, lobar, or mixed).
RESULTS:
CMBs were observed in 8.8% of participants, being mostly lobar (63%). CMB prevalence increased with age (P<0.0001) and was higher in men (P<0.001). Hypertension increased risk of any CMB, and in deep and mixed locations (P<0.05), and low total cholesterol and APOE ε4 increased risk of lobar CMB (P<0.05). Statin use increased risk of lobar and mixed location CMB (P<0.05). The latter association was not affected by adjustment for cholesterol levels or concomitant medication use.
CONCLUSIONS:
We observed the expected association of hypertension with deep CMB and low cholesterol and APOE ε4 with lobar CMB. In addition, statin use was independently associated with CMB risk. This potential adverse effect of statin use needs to be examined in other cohorts.
KEYWORDS:
cerebral small vessel disease; epidemiology; risk factors
PMID:
24713533
PMCID:
DOI:
Lancet Neurol. 2009 May;8(5):453-63. doi: 10.1016/S1474-4422(09)70058-4.
Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention.
Abstract
Despite the inconsistent or weak association between cholesterol and stroke, lowering of cholesterol concentrations with statins reduces the risk of stroke in high-risk populations and in patients with non-cardioembolic stroke or transient ischaemic attack. Statin therapy is the most important advance in stroke prevention since the introduction of aspirin and antihypertensive treatments. Meta-analysis of randomised trials of statins in combination with other preventive strategies, including 165 792 individuals, shows that each 1 mmol/L (39 mg/dL) decrease in LDL cholesterol equates to a reduction in relative risk for stroke of 21.1% (95% CI 6.3-33.5, p=0.009). In secondary prevention of non-cardioembolic stroke, intense reduction of LDL cholesterol by statins also significantly reduced the risk of recurrent stroke (relative risk 0.84, 0.71-0.99, p=0.03) and major cardiovascular events (0.80, 0.69-0.92, p=0.002). Future directions include assessment of a target LDL cholesterol concentration of less than 1.8 mmol/L (70 mg/dL), the effects of triglyceride-lowering therapy alone or in combination with statins, and the effects of treatments to raise HDL cholesterol concentrations.
PMID:
19375663
DOI:
PLoS One. 2014 Mar 18;9(3):e92388. doi: 10.1371/journal.pone.0092388. eCollection 2014.
Statins for the prevention of stroke: a meta-analysis of randomized controlled trials.
Abstract
BACKGROUND:
Stroke is a frequently encountered clinical event that has a detrimental impact on the quality of life. Evidence has increasingly shown that statins can substantially reduce the risk of coronary heart disease. However, it remains to be determined whether statins are definitively effective in preventing stroke.
METHODS:
We systematically searched the PubMed, Embase, and Central databases for studies that compared the effects of statins and placebo in patients at high risk for stroke. The outcome measures were overall incidence of stroke, incidence of fatal stroke, and incidence of hemorrhagic stroke.
RESULTS:
Eighteen randomized controlled trials satisfied all the inclusion criteria for the meta-analysis. The analysis revealed that statinsreduced the overall incidence of stroke than placebo (odds ratio [OR]: 0.80; 95% confidence interval [CI]: 0.74-0.87; P<0.00001). In particular, statins showed efficacy in reducing the incidence of fatal stroke (OR: 0.90; 95% CI: 0.67-1.21; P = 0.47) and hemorrhagic stroke (OR: 0.87; 95% CI: 0.60-1.25; P = 0.45). On the contrary, they were found to increase the overall incidence of stroke (OR: 1.12; 95% CI: 0.89-1.41; P = 0.32) and fatal stroke (OR: 1.37; 95% CI: 0.93-2.03; P = 0.11) in renal transplant recipients and patients undergoing regular hemodialysis.
CONCLUSION:
The results of this analysis suggest that statins may be beneficial in reducing the overall incidence of stroke and they may decrease the risk of fatal stroke and hemorrhagic stroke. However, statins should be used with caution in patients with a history of renal transplantation, regular hemodialysis, transient ischemic attack, or stroke. Further analyses should focus on multicentre, double-blind, placebo-controlled randomized trials with data stratification according to the nature of primary diseases and dose-effect relationship, to clarify the benefits of statins in protection against stroke.
PMID:
24643199
PMCID:
DOI:
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