Statin Treatment in Patients with Acute Ischemic Stroke

Abstract

Background and purpose

We aimed to investigate the association of statin treatment with outcomes in patients with acute ischemic stroke.

Methods

Over a 4.5-year period (starting November 2007), 12 781 patients (mean age, 72·8 ± 12·6 years; 48·6% women) with acute ischemic stroke from 15 hospitals in Schleswig-Holstein, Germany, were enrolled in a population-based study and prospectively evaluated.

The primary outcomes were the mortality during hospitalization and the disability (modified Rankin Scale score ≥2) at discharge from hospital. The secondary outcomes were the mortality and disability at three-months after discharge.

Results

A total of 7535 patients (59%) with acute ischemic stroke were treated with statins. During hospitalization (mean, nine-days), the in-hospital mortality rate (4·7%; 95% confidence interval, 4·3–5·1%) was lower in patients treated with statins than in those without statins (2·3% vs. 7·9%, respectively; P < 0·001). At three-months after discharge, the mortality rate (6·9%; 95% confidence interval, 6·4–7·5%) was lower in patients treated with statins than in those without statins (5·0% vs. 10·6%, respectively; P < 0·001). Adjusted logistic regression analysis showed that statin treatment was associated with reduced rates of in-hospital mortality (odds ratio, 0·39; 95% confidence interval, 0·31–0·48; P < 0·001) and three-month mortality (odds ratio, 0.47; 95% confidence interval, 0·34–0·63; P < 0·001). A comparison of the patient groups revealed that patients on statins were likely to have lower disability rates at discharge (59% vs. 67%, respectively; P < 0·001) and after three-months (33% vs. 42%, respectively; P < 0·001) in patients who had survived the stroke.

Conclusion

Statin treatment may improve the outcomes in patients with acute ischemic stroke. Further studies are necessary to confirm this finding.

Keywords

stroke statin mortality disability plaques hypercholesterolemia

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References

Lloyd-Jones

Adams

Brown

. Heart disease and stroke statistics–2010 update: A report from the American Heart Association. Circulation 2010; 121: e46–215.

Johnston

Mendis

Mathers

. Global variation in stroke burden and mortality: Estimates from monitoring, surveillance, and modelling. Lancet Neurol 2009; 8: 345–54.

Heidenreich

Trogdon

Khavjou

. Forecasting the future of cardiovascular disease in the united states: A policy statement from the American Heart Association. Circulation 2011; 123: 933–44.

Hacke

Furlan

Al-Rawi

. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (dias-2): A prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol 2009; 8: 141–50.

Amarenco

Labreuche

Lavallee

Touboul

. Statins in stroke prevention and carotid atherosclerosis: Systematic review and up-to-date meta-analysis. Stroke 2004; 35: 2902–9.

Amarenco

Bogousslavsky

Callahan

3rd . High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355: 549–59.

Amarenco

Lavallee

Touboul

. Stroke prevention, blood cholesterol, and statins. Lancet Neurol 2004; 3: 271–8.

Cordenier

De Smedt

Brouns

. Pre-stroke use of statins on stroke outcome: A meta-analysis of observational studies. Acta Neurol Belg 2011; 111: 261–7.

Hebert

Gaziano

Chan

Hennekens

. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials. JAMA 1997; 278: 313–21.

10.

Ni Chroinin

Callaly

Duggan

. Association between acute statin therapy, survival, and improved funtional outcome after ischemic stroke: The north dublin population stroke study. Stroke 2011; 42: 1021–9.

11.

Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457–507.

12.

Aslanyan

Weir

McInnes

Reid

Walters

Lees

. Statin administration prior to ischaemic stroke onset and survival: Exploratory evidence from matched treatment-control study. Eur J Neurol 2005; 12: 493–8.

13.

Moonis

Kane

Schwiderski

Sandage

Fisher

. HMG-CoA reductase inhibitors improve acute ischemic stroke outcome. Stroke 2005; 36: 1298–300.

14.

Elkind

Flint

Sciacca

Sacco

. Lipid-lowering agent use at ischemic stroke onset is associated with decreased mortality. Neurology 2005; 65: 253–8.

15.

Kawashima

Yamashita

Miwa

. Hmg-coa reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats. Stroke 2003; 34: 157–63.

16.

Gertz

Laufs

Lindauer

. Withdrawal of statin treatment abrogates stroke protection in mice. Stroke 2003; 34: 551–7.

17.

Flint

Kamel

Navi

. Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival. Stroke 2012; 43: 147–54.

18.

Blanco

Nombela

Castellanos

. Statin treatment withdrawal in ischemic stroke: A controlled randomized study. Neurology 2007; 69: 904–10.

19.

Endres

Laufs

Huang

. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 1998; 95: 8880–5.

20.

Kureishi

Luo

Shiojima

. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 2000; 6: 1004–10.

21.

Ovbiagele

Saver

Starkman

. Statin enhancement of collateralization in acute stroke. Neurology 2007; 68: 2129–31.

22.

Asahi

Huang

Thomas

. Protective effects of statins involving both eNOS and tPA in focal cerebral ischemia. J Cereb Blood Flow Metab 2005; 25: 722–9.

23.

Laufs

Gertz

Huang

. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 2000; 31: 2442–9.

24.

Kunte

Amberger

Busch

Ruckert

Meiners

Harms

. Markers of instability in high-risk carotid plaques are reduced by statins. J Vasc Surg 2008; 47: 513–22.

25.

Goldstein

Amarenco

Szarek

. Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology 2008; 70: 2364–70.

26.

Biffi

Devan

Anderson

. Statin use and outcomes after intracerebral hemorrhage. Neurology 2011; 76: 1581–8.

27.

Diener

Putzki

. Leitlinien für Diagnostik und Therapie in der Neurologie, 4th edn. Stuttgart, Thieme, 2008.

28.

Ni Chroinin

Asplund

Asberg

. Statin therapy and outcome after ischemic stroke: Systematic review and meta-analysis of observational studies and randomized trials. Stroke 2013; 44: 448–56.