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Stroke. 2014 Feb;45(2):509-14. doi: 10.1161/STROKEAHA.113.002751. Epub 2013 Dec 24.

Dose-related effects of statins on symptomatic intracerebral hemorrhage and outcome after thrombolysis for ischemic stroke.

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From Klinik und Hochschulambulanz für Neurologie (J.F.S., S.T., H.J.A., M.E., C.H.N.), Center for Stroke Research (J.F.S., H.J.A., J.B.F., M.E., C.H.N.), and Excellence Cluster NeuroCure (M.E.), Charité-Universitätsmedizin Berlin, Germany; and Department of Neurology and Stroke Unit, University Hospital Basel, Basel, Switzerland (D.J.S., H.G., L.H.B., C.T., P.A.L., S.T.E.).



The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke.


We pooled data from 2 European intravenous thrombolysis registries. Statin doses were stratified in 3 groups according to the attainable lowering of cholesterol levels (low dose: simvastatin 20 mg or equivalent; medium dose: simvastatin 40 mg or equivalent; and high dose: simvastatin 80 mg or equivalent). sICH was defined according to the European Cooperative Acute Stroke Study. Modified Rankin Scale score 0 to 2 at 3 months was considered a favorable outcome.


Among 1446 patients analyzed (median age, 75 years; median initial National Institutes of Health Stroke Scale score, 11; 54% men), 317 (22%) used statins before intravenous thrombolysis. Of them, 120 patients had low-dose, 134 medium-dose, and 63 high-dose statin therapy. sICH occurred in 4% of patients (n=53). Frequency of sICH was 2%, 6%, and 13% in patients with low-, medium-, and high-dose statin treatment, respectively (P<0.01). Adjusted odds ratio (OR) for sICH was 2.4 (95% confidence interval [CI], 1.1-5.3) and 5.3 (95% CI, 2.3-12.3) for patients with medium- and high-dose statins compared with non-statin users. Statin users more often achieved favorable outcome compared with non-statin users (58% versus 51%; P=0.03). An independent association of statin use with favorable outcome was detected (adjusted OR, 1.8; 95% CI, 1.3-2.5). The association was maintained when stratifying for statin dose, although it was not significant in the high-dose group anymore (OR, 1.7; 95% CI, 0.9-3.2).


We observed an association between increasing dose of statin use and risk of sICH after intravenous thrombolysis. Nevertheless, there was an overall beneficial effect of previous statin use on favorable 3-month outcome.


hemorrhage; hydroxymethylglutaryl-CoA reductase inhibitors; stroke; thrombolytic therapy; tissue plasminogen activator

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