Influence of statin therapy at time of stroke onset on functional outcome among patients with atrial fibrillation

Published:October 24, 2016DOI:https://doi.org/10.1016/j.ijcard.2016.10.055

      Abstract

      Background

      Statin pretreatment has been associated with reduced infarct volume in nonlacunar strokes. The effect of statins on functional outcomes of strokes related to atrial fibrillation (AF) is unknown. We aimed to define the influence of prestroke statin use on functional outcome in AF.

      Methods

      We assembled a cohort of consecutive ischemic stroke patients from 2006 to 2010. All patients underwent CT or MRI and were adjudicated by site investigators. AF was confirmed by electrocardiogram in 100% of patients. Site neurologists blinded to the study hypothesis affirmed the type of stroke and assessed the severity of disability at the time of hospital discharge. The frequency of death at 30-days was calculated.

      Results

      Ischemic stroke (n = 1030) resulted in a severe neurological deficit or death (modified Rankin scale ≥4) at 30 days in 711 patients (69%). Using multivariable logistic regression models adjusting for factors associated with statin treatment and factors associated with functional outcome, prestroke statin use was associated with a 32% reduction in frequency of severe stroke (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.50–0.92; P = 0.011). Other independent factors associated with severe stroke included older age, female sex, non-White race, diabetes mellitus, prior ischemic stroke, prior venous thromboembolism, and dementia.

      Conclusion

      Ischemic strokes in AF are associated with high mortality and morbidity. Statin use at time of stroke onset among patients with AF was associated in this study with less severe stroke and warrant validation.

      Keywords

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      References

        • Hathcock J.J.
        Flow effects on coagulation and thrombosis.
        Arterioscler. Thromb. Vasc. Biol. 2006; 26: 1729-1737
        • Lin H.J.
        • Wolf P.A.
        • Kelly-Hayes M.
        • Beiser A.S.
        • Kase C.S.
        • Benjamin E.J.
        • et al.
        Stroke severity in atrial fibrillation. The Framingham study.
        Stroke. 1996; 27: 1760-1764
        • Hylek E.M.
        • Go A.S.
        • Chang Y.
        • Jensvold N.G.
        • Henault L.E.
        • Selby J.V.
        • et al.
        Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.
        N. Engl. J. Med. 2003; 349: 1019-1026
        • Eto M.
        • Kozai T.
        • Cosentino F.
        • Joch H.
        • Luscher T.F.
        Statin prevents tissue factor expression in human endothelial cells: role of rho/rho-kinase and Akt pathways.
        Circulation. 2002; 105: 1756-1759
        • Undas A.
        • Brummel K.E.
        • Musial J.
        • Mann K.G.
        • Szczeklik A.
        Simvastatin depresses blood clotting by inhibiting activation of prothrombin, factor V, and factor XIII and by enhancing factor Va inactivation.
        Circulation. 2001; 103: 2248-2253
        • Pignatelli P.
        • Carnevale R.
        • Pastori D.
        • Cangemi R.
        • Napoleone L.
        • Bartimoccia S.
        • et al.
        Immediate antioxidant and antiplatelet effect of atorvastatin via inhibition of Nox2.
        Circulation. 2012; 126: 92-103
        • Wells P.S.
        • Gebel M.
        • Prins M.H.
        • Davidson B.L.
        • Lensing A.W.
        Influence of statin use on the incidence of recurrent venous thromboembolism and major bleeding in patients receiving rivaroxaban or standard anticoagulant therapy.
        Thromb. J. 2014; 12: 26
        • Glynn R.J.
        • Danielson E.
        • Fonseca F.A.
        • Genest J.
        • Gotto Jr., A.M.
        • Kastelein J.J.
        • et al.
        A randomized trial of rosuvastatin in the prevention of venous thromboembolism.
        N. Engl. J. Med. 2009; 360: 1851-1861
        • Shook S.J.
        • Gupta R.
        • Vora N.A.
        • Tievsky A.L.
        • Katzan I.
        • Krieger D.W.
        Statin use is independently associated with smaller infarct volume in nonlacunar MCA territory stroke.
        J. Neuroimaging. 2006; 16: 341-346
        • Nicholas J.S.
        • Swearingen C.J.
        • Thomas J.C.
        • Rumboldt Z.
        • Tumminello P.
        • Patel S.J.
        The effect of statin pretreatment on infarct volume in ischemic stroke.
        Neuroepidemiology. 2008; 31: 48-56
        • Hayden D.T.
        • Hannon N.
        • Callaly E.
        • Nii Chroiiniin D.
        • Horgan G.
        • Kyne L.
        • et al.
        Rates and determinants of 5-year outcomes after atrial fibrillation-related stroke: a population study.
        Stroke. 2015; 46: 3488-3493
        • Ni Chroinin D.
        • Asplund K.
        • Asberg S.
        • Callaly E.
        • Cuadrado-Godia E.
        • Diez-Tejedor E.
        • et al.
        Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials.
        Stroke. 2013; 44: 448-456
        • Adams Jr., H.P.
        • del Zoppo G.
        • Alberts M.J.
        • Bhatt D.L.
        • Brass L.
        • Furlan A.
        • et al.
        Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association stroke council, clinical cardiology council, cardiovascular radiology and intervention council, and the atherosclerotic peripheral vascular disease and quality of care outcomes in research interdisciplinary working groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.
        Circulation. 2007; 115: e478-e534
        • Hatano S.
        Experience from a multicentre stroke register: a preliminary report.
        Bull. World Health Organ. 1976; 54: 541-553
        • January C.T.
        • Wann L.S.
        • Alpert J.S.
        • Calkins H.
        • Cigarroa J.E.
        • Cleveland J.C.
        • et al.
        2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society.
        J. Am. Coll. Cardiol. 2014; 64: 2246-2280
        • Rankin J.
        Cerebrovascular accidents in patients over 65 years of age: prognosis.
        Scott. Med. J. 1957; 2: 200-205
        • van Swieten J.
        • Koudstaal P.
        • Visser M.
        • Schouten H.
        • van Gijn J.
        Interobserver agreement for the assessment of handicap in stroke patients.
        Stroke. 1988; 19: 604-607
        • Watson T.
        • Shantsila E.
        • Lip G.Y.
        Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited.
        Lancet. 2009; 373: 155-166
        • Lim H.S.
        • Blann A.D.
        • Lip G.Y.
        Soluble CD40 ligand, soluble P-selectin, interleukin-6, and tissue factor in diabetes mellitus: relationships to cardiovascular disease and risk factor intervention.
        Circulation. 2004; 109: 2524-2528
        • Petrauskiene V.
        • Falk M.
        • Waernbaum I.
        • Norberg M.
        • Eriksson J.W.
        The risk of venous thromboembolism is markedly elevated in patients with diabetes.
        Diabetologia. 2005; 48: 1017-1021
        • Hansen H.R.
        • Wolfs J.L.
        • Bruggemann L.
        • Sommeijer D.W.
        • Bevers E.
        • Hauer A.D.
        • et al.
        Hyperglycemia accelerates arterial thrombus formation and attenuates the antithrombotic response to endotoxin in mice.
        Blood Coagul. Fibrinolysis. 2007; 18: 627-636
        • Mahmoodi B.
        • Gansevoort R.
        • Veeger N.
        • Matthews A.
        • Navis G.
        • Hillege H.
        • et al.
        Microalbuminuria and risk of venous thromboembolism.
        JAMA. 2009; 301: 1790-1797
        • Martinez-Sanchez P.
        • Rivera-Ordonez C.
        • Fuentes B.
        • Ortega-Casarrubios M.A.
        • Idrovo L.
        • Diez-Tejedor E.
        The beneficial effect of statins treatment by stroke subtype.
        Eur. J. Neurol. 2009; 16: 127-133
        • Reeves M.J.
        • Gargano J.W.
        • Luo Z.
        • Mullard A.J.
        • Jacobs B.S.
        • Majid A.
        • et al.
        Effect of pretreatment with statins on ischemic stroke outcomes.
        Stroke. 2008; 39: 1779-1785
        • Badheka A.O.
        • Rathod A.
        • Kizilbash M.A.
        • Garg N.
        • Mohamad T.
        • Afonso L.
        • et al.
        Impact of lipid-lowering therapy on outcomes in atrial fibrillation.
        Am. J. Cardiol. 2010; 105: 1768-1772
        • Lee M.J.
        • Bang O.Y.
        • Kim S.J.
        • Kim G.M.
        • Chung C.S.
        • Lee K.H.
        • et al.
        Role of statin in atrial fibrillation-related stroke: an angiographic study for collateral flow.
        Cerebrovasc. Dis. 2014; 37: 77-84
        • Ovbiagele B.
        • Saver J.L.
        • Starkman S.
        • Kim D.
        • Ali L.K.
        • Jahan R.
        • et al.
        Statin enhancement of collateralization in acute stroke.
        Neurology. 2007; 68: 2129-2131
        • Chaudagar K.K.
        • Mehta A.A.
        Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats.
        Can. J. Physiol. Pharmacol. 2014; 92: 338-349
        • Zhou J.
        • Cheng M.
        • Liao Y.H.
        • Hu Y.
        • Wu M.
        • Wang Q.
        • et al.
        Rosuvastatin enhances angiogenesis via eNOS-dependent mobilization of endothelial progenitor cells.
        PLoS One. 2013; 8e63126
        • Violi F.
        • Calvieri C.
        • Ferro D.
        • Pignatelli P.
        Statins as antithrombotic drugs.
        Circulation. 2013; 127: 251-257
        • Colli S.
        • Eligini S.
        • Lalli M.
        • Camera M.
        • Paoletti R.
        • Tremoli E.
        Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 265-272
        • Undas A.
        • Celinska-Lowenhoff M.
        • Brummel-Ziedins K.E.
        • Brozek J.
        • Szczeklik A.
        • Mann K.G.
        Simvastatin given for 3 days can inhibit thrombin generation and activation of factor V and enhance factor Va inactivation in hypercholesterolemic patients.
        Arterioscler. Thromb. Vasc. Biol. 2005; 25: 1524-1525
        • Hanson S.R.
        • Griffin J.H.
        • Harker L.A.
        • Kelly A.B.
        • Esmon C.T.
        • Gruber A.
        Antithrombotic effects of thrombin-induced activation of endogenous protein C in primates.
        J. Clin. Invest. 1993; 92: 2003-2012
        • Tannous M.
        • Cheung R.
        • Vignini A.
        • Mutus B.
        Atorvastatin increases ecNOS levels in human platelets of hyperlipidemic subjects.
        Thromb. Haemost. 1999; 82: 1390-1394
        • Puccetti L.
        • Santilli F.
        • Pasqui A.L.
        • Lattanzio S.
        • Liani R.
        • Ciani F.
        • et al.
        Effects of atorvastatin and rosuvastatin on thromboxane-dependent platelet activation and oxidative stress in hypercholesterolemia.
        Atherosclerosis. 2011; 214: 122-128
        • Sola S.
        • Mir M.Q.
        • Lerakis S.
        • Tandon N.
        • Khan B.V.
        Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure.
        J. Am. Coll. Cardiol. 2006; 47: 332-337