Primary and secondary prevention of cerebral ischemia

Classification of level of evidence

↑↑ Efficacy and usefulness is well supported by multiple appropriate clinical studies (i.e. controlled randomized trials), either one or more metaanalyses or systematic reviews.

↑Efficacy and usefulness is supported by at least one appropriate clinical study (i.e. controlled randomized trial).

↓↓ Lack of efficacy is well supported by one or more appropriate clinical studies (i.e. controlled randomized trial), either one or more metaanalyses or systematic reviews.

↔ No study results exist to prove any benefit or harm. This can be due lack of appropriate studies, or several studies with controversial results.

Literature

• 1 Abbott R D, Rodriguez B L, Burchfiel C M. et al . Physical activity in older middle-aged men and reduced risk of stroke: the Honolulu Heart Program.  Am J Epidemiol. 1994;  139 881-893
• 2 Abou-Chebl A, Yadav J S, Reginelli J P. et al . Intracranial hemorrhage and hyperperfusion syndrome following carotid artery stenting: risk factors, prevention, and treatment.  J Am Coll Cardiol. 2004;  43 1596-1601
• 3 Adams Jr H P, Effron M B, Torner J. et al . Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II).  Stroke. 2008;  39 87-99
• 4 Akins P T, Feldman H A, Zoble R G. et al . Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials.  Stroke. 2007;  38 874-880
• 5 Algra A, de Schryver E, van Gijn J. et al . Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin.  Cochrane Database Syst Rev. 2006;  3 , CD 001342
• 6 Algra A, van Gijn J. Cumulative meta-analysis of aspirin efficacy after cerebral ischaemia of arterial origin.  J Neurol Neurosurg Psychiatry. 1999;  65 255
• 7 Amarenco P, Goldstein L B, Szarek M. et al . Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.  Stroke. 2007;  38 3198-3204
• 8 Amarenco P, Labreuche J, Lavallee P. et al . Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis.  Stroke. 2004;  35 2902-2909
• 9 Anderson G, Limacher M, Assaf A. et al . Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial.  J Am Med Ass. 2004;  291 1701-1712
• 10 Ansell J, Hirsh J, Dalen J. et al . Managing oral anticoagulant therapy.  Chest. 2001;  119 (Suppl 1) 22S-38S
• 11 Antiplatelet Trialists’ Collaboration . Collaborative overview of randomised trials of antiplatelet therapy – I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.  Br Med J. 1994;  308 81-106
• 12 Antithrombotic Trialists’ Collaboration . Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.  Br Med J. 2002;  524 71-86
• 13 Anzola G, Morandi E, Casilli F. et al . Does transcatheter closure of patent foramen ovale really „shut the door?” – a prospective study with transcranial doppler.  Stroke. 2004;  35 2140-2144
• 14 Barnett H J, Taylor D W, Eliasziw M. et al . Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis.  N Engl J Med. 1998;  339 1415-1425
• 15 Bejot Y, Benatru I, Rouaud O. et al . Epidemiology of stroke in Europe: geographic and environmental differences.  J Neurol Sci. 2007;  262 85-88
• 16 Beletsky V, Nadareishvili Z, Lynch J. et al . Cervical arterial dissection. Time for a therapeutic trial?.  Stroke. 2003;  34 2856-2860
• 17 Bhatt D L, Flather M D, Hacke W. et al . Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.  J Am Coll Cardiol. 2007;  49 1982-1988
• 18 Blanco M, Nombela F, Castellanos M. et al . Statin treatment withdrawal in ischemic stroke: a controlled randomized study.  Neurology. 2007;  69 904-910
• 19 Bonaa K H, Njolstad I, Ueland P M. et al . Homocysteine lowering and cardiovascular events after acute myocardial infarction.  N Engl J Med. 2006;  354 1578-1588
• 20 Bond R, Rerkasem K, Rothwell P M. Systematic review of the risks of carotid endarterectomy in relation to the clinical indication for and timing of surgery.  Stroke. 2003;  34 2290-2303
• 21 Bond R, Rerkasem K, Shearman C P. et al . Time trends in the published risks of stroke and death due to endarterectomy for symptomatic carotid stenosis.  Cerebrovasc Dis. 2004;  18 37-46
• 22 Born G, Patrono C. Antiplatelet drugs.  Br J Pharmacol. 2006;  147 (Suppl 1) S 241-S 251
• 23 Burry K. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative randomized controlled trial.  Curr Womens Health Rep. 2002;  2 331-332
• 24 Burton A. Abciximab extends treatment window for stroke.  Lancet Neurology. 2003;  2 390
• 25 Cannegieter S, Rosendaal F, Wintzen A. et al . Optimal oral anticoagulant therapy in patients with mechanical heart valves.  N Engl J Med. 1995;  333 11-17
• 26 Cannon C P, Braunwald E, McCabe C H. et al . Intensive versus moderate lipid lowering with statins after acute coronary syndromes.  N Engl J Med. 2004;  350 1495-1504
• 27 CAPRIE Steering Committee . A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).  Lancet. 1996;  348 1329-1339
• 28 Chan F, Ching J, Hung L. et al . Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.  N Engl J Med. 2005;  352 238-244
• 29 Chimowitz M I, Lynn M J, Howlett-Smith H. et al . Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis.  N Engl J Med. 2005;  352 1305-1316
• 30 Cholesterol Treatment Trialists’ (CTT) Collaborators . Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis.  Lancet. 2008;  371 117-125
• 31 Christensen R, Kristensen P K, Bartels E M. et al . Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.  Lancet. 2007;  370 1706-1713
• 32 Colhoun H M, Betteridge D J, Durrington P N. et al . Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.  Lancet. 2004;  364 685-696
• 33 Collaborative Group of the Primary Prevention Project (PPP) . Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice.  Lancet. 2001;  357 89-95
• 34 Collins R, Armitage J, Parish S. et al . Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20,536 people with cerebrovascular disease or other high-risk conditions.  Lancet. 2004;  363 757-767
• 35 Collins R, Peto R, MacMahon S. et al . Blood pressure, stroke and coronary heart disease. Part 2, short-term reductions in blood pressure: overview of randomized drug trials in their epidemiological context.  Lancet. 1990;  335 827-838
• 36 Connolly S, Pogue J, Hart R. et al . Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial.  Lancet. 2006;  367 1903-1912
• 37 Curioni C, Andre C, Veras R. Weight reduction for primary prevention of stroke in adults with overweight or obesity.  Cochrane Database Syst Rev. 2006;  (4) , CD 006062
• 38 Dahlof B, Devereux R B, Kjeldsen S E. et al . Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.  Lancet. 2002;  359 995-1003
• 39 Dahlof B, Sever P S, Poulter N R. et al . Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial.  Lancet. 2005;  366 895-906
• 40 de Lemos J A, Blazing M A, Wiviott S D. et al . Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial.  J Am Med Ass. 2004;  292 1307-1316
• 41 Diener H C. Modified-release dipyridamole combined with aspirin for secondary stroke prevention.  Aging Health. 2005;  1 19-26
• 42 Diener H, Bogousslavsky J, Brass L. et al . Acetylsalicylic acid on a background of clopidogrel in high-risk patients randomised after recent ischaemic stroke or transient ischaemic attack: The MATCH trial results.  Lancet. 2004a;  364 331-334
• 43 Diener H C, Cuhna L, Forbes C. et al . European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.  J Neurol Sci. 1996;  143 1-13
• 44 Diener H C, Darius H, Bertrand-Hardy J M. et al . Cardiac safety in the European stroke prevention study 2 (ESPS 2).  Int J Clin Pract. 2001;  55 162-163
• 45 Diener H C, Ringleb P A, Savi P. Clopidogrel for secondary prevention of stroke.  Expert Opin Pharmacother. 2005;  6 755-764
• 46 Diener H C, Sacco R, Yusuf S. et al . Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens and telmisartan versus placebo in patients with strokes: the prevention regimen for effectively avoiding second strokes (PRoFESS) trial.  Cerebrovasc Dis. 2007;  23 368-380
• 47 Diener H, Welch K, Mohr J. Migraine and stroke. In: Mohr J, Choi D, Grotta J, Weir B, Wolf PA, eds Stroke. Pathophysiology, diagnosis and management. Philadelphia; Churchill Livingstone 2004b: 629-640
• 48 Droste D, Ritter M, Dittrich R. et al . Arterial hypertension and ischaemic stroke.  Acta Neurol Scand. 2003;  107 241-251
• 49 EAFT Group . Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke.  Lancet. 1993;  342 1255-1262
• 50 Endres M. Statins and stroke.  J Cereb Blood Flow Metab. 2005;  25 1093-1110
• 51 Endres M, Laufs U. Discontinuation of statin treatment in stroke patients.  Stroke. 2006;  37 2640-2643
• 52 European Carotid Surgery Trialists’ Collaborative Group . MRC European carotid surgery trial: interim results for symptomatic patients with severe carotid stenosis and with mild carotid stenosis.  Lancet. 1991;  337 1235-1243
• 53 European Carotid Surgery Trialists’ Collaborative Group . Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).  Lancet. 1998;  351 1379-1387
• 54 Executive Committee for the Asymptomatic Carotid Atherosclerosis Study . Endarterectomy for asymptomatic carotid artery stenosis.  J Am Med Ass. 1995;  273 1421-1428
• 55 Ferguson G G, Eliasziw M, Barr H WK. et al . The North American symptomatic carotid endarterectomy trial: surgical result in 1415 patients.  Stroke. 1999;  30 1751-1758
• 56 Fiebach J B, Schellinger P D, Jansen O. et al . CT and diffusion-weighted MR imaging in randomized order: diffusion-weighted imaging results in higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke.  Stroke. 2002;  33 2206-2210
• 57 Flather M D, Yusuf S, Kober L. et al . Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients.  Lancet. 2000;  355 1575-1581
• 58 Fuster V, Ryden L E, Cannom D S. et al . ACC / AHA / ESC 2006 guidelines for the management of patients with atrial fibrillation [full text: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 guidelines for the management of patients with atrial fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society].  Europace. 2006;  8 651-745
• 59 Gaede P, Vedel P, Larsen N. et al . Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.  N Engl J Med. 2003;  348 383-393
• 60 Gage B F, Waterman A D, Shannon W. et al . Validation of clinical classification schemes for predicting stroke results from the national registry of atrial fibrillation.  J Am Med Ass. 2001;  285 2864-2870
• 61 Giles M F, Rothwell P M. Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis.  Lancet Neurol. 2007;  6 1063-1072
• 62 Gilon D, Bounanno F S, Joffe M M. et al . Lack of evidence of an association between mitral-valve prolapse and stroke in young patients.  N Engl J Med. 1999;  341 8-13
• 63 Goldstein L B, Adams R, Becker K J. et al . Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association.  Stroke. 2001;  32 280-299
• 64 Goldstein L B, Amarenco P, Szarek M. et al . Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study.  Neurology. 2007;  68 737-742
• 65 Gonzales D, Rennard S I, Nides M. et al . Varenicline, an alpha-4 beta-2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.  J Am Med Ass. 2006;  296 47-55
• 66 Grady D, Herrington D, Bittner V. et al . Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen / progestin Replacement Study follow-up (HERS II).  J Am Med Ass. 2002;  288 99-101
• 67 Grau A J, Weimar C, Buggle F. et al . Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank.  Stroke. 2001;  32 2559-2566
• 68 Grundy S M, Cleeman J I, Merz C N. et al . Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.  J Am Coll Cardiol. 2004;  44 720-732
• 69 Hacke W, Donnan G, Fieschi C. et al . Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.  Lancet. 2004;  363 768-774
• 70 Halliday A, Mansfield A, Marro J. et al . Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.  Lancet. 2004;  363 1491-1502
• 71 Handke M, Harloff A, Olschewski M. et al . Patent foramen ovale and cryptogenic stroke in older patients.  N Engl J Med. 2007;  357 2262-2268
• 72 Hansson L, Lindholm L H, Ekbom T. et al . Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in old patients with hypertension-2 study.  Lancet. 1999;  354 1751-1756
• 73 Hardman S MC, Cowie M R. Anticoagulation in heart disease.  Br Med J. 1999;  318 238-244
• 74 Hart R, Benavente O, McBride R. et al . Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.  Ann Intern Med. 1999;  131 492-501
• 75 Hart R, Pearce L, Miller V. et al . Cardioembolic versus noncardioembolic strokes in atrial fibrillation: Frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies.  Cerebrovasc Dis. 2000a;  10 39-43
• 76 Hart R G, Halperin J L. Atrial fibrillation and stroke: concepts and controversies.  Stroke. 2001;  32 803-808
• 77 Hart R G, Halperin J L, McBride R. et al . Aspirin for the primary prevention of stroke and other major vascular events. Meta-analysis and hypotheses.  Arch Neurol. 2000b;  57 326-332
• 78 Heart Protection Study Collaborative Group . MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in high-risk individuals: a randomised placebo-controlled trial.  Lancet. 2002;  360 7-22
• 79 Heuschmann P U, Heidrich J, Wellmann J. et al . Stroke mortality and morbidity attributable to passive smoking in Germany.  Eur J Cardiovasc Prev Rehabil. 2007;  14 793-795
• 80 Hill M D, Yiannakoulias N, Jeerakathil T. et al . The high risk of stroke immediately after transient ischemic attack: a population-based study.  Neurology. 2004;  62 2015-2020
• 81 Homma S, Sacco R L, Di Tullio M R. et al . Effect of medical treatment in stroke patients with patent foramen ovale.  Circulation. 2002;  105 2625-2631
• 82 Hughes J R, Stead L F, Lancaster T. Antidepressants for smoking cessation.  Cochrane Database Syst Rev. 2007;  (1) , CD 000031
• 83 Hylek E M, Evans-Molina C, Shea C. et al . Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation.  Circulation. 2007;  115 2689-2696
• 84 International Society of Hypertension Writing Group . International Society of Hypertension (ISH): Statement on the Management of Blood Pressure in Acute Stroke.  Journal of Hypertension. 2003;  21 665-672
• 85 Iso H, Date C, Yamamoto A. et al . Smoking cessation and mortality from cardiovascular disease among Japanese men and women: the JACC Study.  Am J Epidemiol. 2005;  161 170-179
• 86 Iso H, Hennekens C H, Stampfer M J. et al . Prospective study of aspirin use and risk of stroke in women.  Stroke. 1999;  30 1764-1771
• 87 Iso H, Jacobs D R, Wentworth D. et al . Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial.  N Engl J Med. 1989;  320 904-910
• 88 Johnston S C, Gress D R, Browner W S. et al . Short-term prognosis after emergency department diagnosis of TIA.  J Am Med Ass. 2000;  284 2901-2906
• 89 Jorenby D E, Hays J T, Rigotti N A. et al . Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.  J Am Med Ass. 2006;  296 56-63
• 90 Junghans U, Seitz R J, Aulich A. et al . Bleeding risk of tirofiban, a nonpeptide GPIIb/IIIa platelet receptor antagonist in progressive stroke: An open pilot study.  Cerebrovasc Dis. 2001;  12 308-312
• 91 Kasner S E, Chimowitz M I, Lynn M J. et al . Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis.  Circulation. 2006;  113 555-563
• 92 Kawachi I, Colditz G A, Stampfer M J. et al . Smoking cessation and decreased risk of stroke in women.  J Am Med Ass. 1993;  269 232-236
• 93 Keil U, Becher H, Heidrich J. et al . Passivrauchbedingte Morbidität und Mortalität in Deutschland. In: Deutsches Krebsforschungszentrum Heidelberg, Hrsg Passivrauchen – ein unterschätztes Gesundheitsrisiko. Heidelberg; 2006: 20-59
• 94 Kern R, Ringleb P A, Hacke W. et al . Stenting for carotid artery stenosis.  Nat Clin Pract Neurol. 2007;  3 212-220
• 95 Khairy P, O’Donnell C P, Landzberg M J. Transcatheter closure versus medical therapy of patent foramen ovale and presumed paradoxical thromboemboli: a systematic review.  Ann Intern Med. 2003;  139 753-760
• 96 Khaw K T. Epidemiology of stroke.  J Neurol Neurosurg Psychiatry. 1996;  61 333-338
• 97 Kiely D K, Wolf P A, Cupples L A. et al . Physical activity and stroke risk: the Framingham Study.  Am J Epidemiol. 1994;  140 608-620
• 98 Kurth T, Gaziano J M, Berger K. et al . Body mass index and the risk of stroke in men.  Arch Intern Med. 2002;  162 2557-2562
• 99 Lam T H, Li Z B, Ho S Y. et al . Smoking, quitting and mortality in an elderly cohort of 56,000 Hong Kong Chinese.  Tob Control. 2007;  16 182-189
• 100 LaRosa J C, Grundy S M, Waters D D. et al . Intensive lipid lowering with atorvastatin in patients with stable coronary disease.  N Engl J Med. 2005;  352 1425-1435
• 101 Lee C, Folsom A, Blair S. Physical activity and stroke risk: A meta-analysis.  Stroke. 2003;  34 2475-2481
• 102 Lee I M, Hennekens C H, Berger K. et al . Exercise and risk of stroke in male physicians.  Stroke. 1999;  30 1-6
• 103 Leppala J M, Virtamo J, Fogelholm R. et al . Different risk factors for different stroke subtypes: association of blood pressure, cholesterol, and antioxidants.  Stroke. 1999;  30 2535-2540
• 104 Lewington S, Whitlock G, Clarke R. et al . Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths.  Lancet. 2007;  370 1829-1839
• 105 Lindholm L H, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis.  Lancet. 2005;  366 1545-1553
• 106 Lindholm L H, Ibsen H, Dahlof B. et al . Cardiovascular morbidity and mortality in patients with diabetes in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.  Lancet. 2002;  359 1004-1010
• 107 Lovett J, Coull A, Rothwell P. Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies.  Neurology. 2004;  62 569-573
• 108 Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection.  Stroke. 2004;  35 613-614
• 109 Mant J, Hobbs F, Fletcher K. et al . Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial.  Lancet. 2007;  370 493-503
• 110 Mas J L, Arquizan C, Lamy C. et al . Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both.  N Engl J Med. 2001;  345 1740-1746
• 111 Mas J L. et al, for the EVA-3S Investigators . Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis.  N Engl J Med. 2006;  355 1660-1671
• 112 Merikangas K R, Fenton B T, Cheng S H. et al . Association between migraine and stroke in a large-scale epidemiological study of the United States.  Arch Neurol. 1997;  54 362-368
• 113 Messe S, Silverman I, Kizer J. et al . Practice parameter: recurrent stroke with patent foramen ovale and atrial septal aneurysm: report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology. 2004;  62 1042-1050
• 114 Mohr J P, Thompson J L, Lazar R M. et al . A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.  N Engl J Med. 2001;  345 1444-1451
• 115 Moore W S, Vescera C L, Robertson J T. et al . Selection process for surgeons in the asymptomatic carotid atherosclerosis study.  Stroke. 1991;  22 1353-1357
• 116 Neter J E, Stam B E, Kok F J. et al . Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials.  Hypertension. 2003;  42 878-884
• 117 Nieuwlaat R, Capucci A, Camm A J. et al . Atrial fibrillation management: a prospective survey in ESC member countries: the Euro Heart Survey on Atrial Fibrillation.  Eur Heart J. 2005;  26 2422-2434
• 118 Overell J R, Bone I, Less K R. Interatrial septal abnormalities and stroke. A meta-analysis of case-control studies.  Neurology. 2000;  55 1172-1179
• 119 Paciaroni M, Hennerici M, Agnelli G. et al . Statins and stroke prevention.  Cerebrovasc Dis. 2007;  24 170-182
• 120 Patrono C, Garcia R odriguez, Landolfi R. et al . Low-dose aspirin for the prevention of atherothrombosis.  N Engl J Med. 2005;  353 2373-2383
• 121 Peto R, Gray R, Collins R. et al . Randomised trial of prophylactic daily aspirin in British male doctors.  Brit Med J. 1988;  296 313-316
• 122 Pi-Sunyer F X, Aronne L J, Heshmati H M. et al . Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial.  J Am Med Ass. 2006;  295 761-775
• 123 Progress Collaborative Group . Randomised trial of a perindopril-based blood-pressure lowering regimen among individuals with previous stroke or transient ischaemic attack.  Lancet. 2001;  358 1033-1041
• 124 Rashid P, Leonardi-Bee J, Bath P. Blood pressure reduction and secondary prevention of stroke and other vascular events. A systematic review.  Stroke. 2003;  34 2741-2749
• 125 Ridker P M, Cook N R, Lee I M. et al . A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.  N Engl J Med. 2005;  352 1293-1304
• 126 Ringleb P A, Allenberg J, Bruckmann H. et al . 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.  Lancet. 2006;  368 1239-1247
• 127 Rothwell P, Eliasziw M, Gutnikov S. et al . Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.  Lancet. 2004;  363 915-924
• 128 Rothwell P M, Eliasziv M, Gutnikov S A. et al . Analysis of pooled data from the randomized controlled trials of endarterectomy for symptomatic carotid stenosis.  Lancet. 2003;  361 107-116
• 129 Rothwell P M, Warlow C P. on behalf of the European Carotid Surgery Trialists' Collaborative Group . Prediction of benefit from carotid endarterectomy in individual patients: a risk-modelling study.  Lancet. 1999;  353 2105-2110
• 130 Sacks F M, Svetkey L P, Vollmer W M. et al . Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet.  N Engl J Med. 2001;  344 3-10
• 131 Salem D N, Levine H J, Pauker S G. et al . Antithrombotic therapy in valvular heart disease.  Chest. 1998;  114 (Suppl) 590S-601S
• 132 Saxena R, Koudstaal P J. Anticoagulants for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack.  Stroke. 2004;  35 1782-1783
• 133 Scheen A J, Finer N, Hollander P. et al . Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study.  Lancet. 2006;  368 1660-1672
• 134 Schrader J, Lüders S, Kulschewski A. et al . The ACCESS Study: evaluation of acute candesartan cilexetil therapy in stroke survivors.  Stroke. 2003;  34 1699-1703
• 135 Schrader J, Lüders S, Kulschewski A. et al . Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOSES).  Stroke. 2005;  36 1218-1226
• 136 Seitz R, Hamzavi M, Junghans U. et al . Thrombolysis with recombinant tissue plasminogen activator and tirofiban in stroke: preliminary observations.  Stroke. 2003;  34 1932-1935
• 137 Sever P, Dahlof B, Poulter N. et al . Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.  Lancet. 2003;  361 1149-1158
• 138 Shahar E, Chambless L, Rosamond W. et al . Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study.  Stroke. 2003;  34 623-631
• 139 Shepherd J, Blauw G J, Murphy M B. et al . Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.  Lancet. 2002;  360 1623-1630
• 140 Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke.  Br Med J. 1989;  298 789-794
• 141 Singer D E, Albers G W, Dalen J E. et al . Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126 (Suppl 3) 429S-456S
• 142 Slottow T L, Steinberg D H, Waksman R. Overview of the 2007 Food and Drug Administration Circulatory System Devices Panel meeting on patent foramen ovale closure devices.  Circulation. 2007;  116 677-682
• 143 Staessen J A, Gasowski J, Wang J G. et al . Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials.  Lancet. 2000;  355 865-872
• 144 Staessen J A, Wang J G, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis.  Lancet. 2001;  358 1305-1315
• 145 Stingele R, Berger J, Alfke K. et al . Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.  Lancet Neurology. 2008;  7 216-222
• 146 Stratton I M, Adler A I, Neil H AW. et al . Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.  Br J Med. 2000;  321 405-412
• 147 The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group . Major cardiovascular events in hypertensive patients randomized to doxazosin versus chlorthalidone. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).  J Am Med Ass. 2000;  283 1967-1975
• 148 The ESPRIT Study Group . Aspirin plus Dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.  Lancet. 2006;  367 1665-1673
• 149 The ESPRIT Study Group . Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial.  Lancet Neurology. 2007;  6 115-124
• 150 The ESPS Group . The European Stroke Prevention Study (ESPS). Principal end-points.  Lancet. 1987;  ii 1351-1354
• 151 The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators . Homocysteine lowering with folic acid and B vitamins in vascular disease.  N Engl J Med. 2006;  354 1567-1577
• 152 The Steering Committee of the Physicians’ Health Study Research Group . Aspirin for the primary prevention of myocardial infarction.  N Engl J Med. 1988;  318 245-264
• 153 The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators . High-dose atorvastatin after stroke or transient ischemic attack.  N Engl J Med. 2006;  355 549-559
• 154 The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group . A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin.  Ann Neurol. 1997;  42 857-865
• 155 Toole J F, Malinow M R, Chambless L E. et al . Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.  J Am Med Ass. 2004;  291 565-575
• 156 Topol E, Easton D, Harrington R. et al . Randomized, double-blind, placebo-controlled, international trial of the oral IIb / IIIa antagonist lotrafiban in coronary and cerebrovascular disease.  Circulation. 2003;  108 16-23
• 157 Topol E J, Byzova T V, Plow E F. Platelet GPIIb-IIIa blockers.  Lancet. 1999;  353 227-231
• 158 Turner R, Cull C, Frighi V. et al . Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group.  J Am Med Ass. 1999;  281 2005-2012
• 159 UK Prospective Diabetes Study (UKPDS) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.  Lancet. 1998;  352 837-853
• 160 Viscoli C M, Brass L M, Kernan W N. et al . A clinical trial of estrogen-replacement therapy after ischemic stroke.  N Engl J Med. 2001;  345 1243-1249
• 161 Wannamethee S G, Shaper A G, Ebrahim S. HDL-Cholesterol, total cholesterol and the risk of stroke in middle-aged British men.  Stroke. 2000;  31 1882-1888
• 162 Wannamethee S G, Shaper A G, Whincup P H. et al . Smoking cessation and the risk of stroke in middle-aged men.  J Am Med Ass. 1995;  274 155-160
• 163 Waters D D, Schwartz G G, Olsson A G. et al . Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy.  Circulation. 2002;  106 1690-1695
• 164 Weimar C, Goertler M, Rother J. et al . Systemic Risk Score Evaluation in Ischemic Stroke Patients (SCALA): A prospective cross sectional study in 85 German stroke units.  J Neurol. 2007;  254 1562-1568
• 165 Weimar C, Roth M P, Zillessen G. et al . Complications following acute ischemic stroke.  Eur Neurol. 2002;  48 133-140
• 166 Wilcox R, Bousser M G, Betteridge D J. et al . Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04).  Stroke. 2007;  38 865-873
• 167 Wilson P W, Garrison R J, Castelli W P. Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. The Framingham Study.  N Engl J Med. 1985;  313 1038-1043
• 168 Wilson P WF, Hoeg J M, D’Agostino R B. et al . Cumultative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis.  N Engl J Med. 1997;  337 516-522
• 169 Windecker S, Wahl A, Chatterjee T. et al . Percutaneous closure of patent foramen ovale in patients with paradoxical embolism: long-term risk of recurrent thromboembolic events.  Circulation. 2000;  101 893-898
• 170 Wolf P A, Cobb J L, D’Agostino R B. Epidemiology of stroke. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM, eds Stroke: pathophysiology, diagnosis and management. New York; Churchill Livingston 1992: 3-27
• 171 Yadav J S, Wholey M H, Kuntz R E. et al . Protected carotid-artery stenting versus endarterectomy in high-risk patients.  N Engl J Med. 2004;  351 1493-1501
• 172 Yusuf S, Zhao F, Mehta S R. et al . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.  N Engl J Med. 2001;  345 494-502