Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER). Circulation. 2010;121:143 150. 161. McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke. 2012;43:2149 2156. 162. Hackam DG, Woodward M, Newby LK, Bhatt DL, Shao M, Smith EE, Donner A, Mamdani M, Douketis JD, Arima H, Chalmers J, MacMahon S, Tirschwell DL, Psaty BM, Bushnell CD, Aguilar MI, Capampangan DJ, Werring DJ, De Rango P, Viswanathan A, Danchin N, Cheng CL, Yang YH, Verdel BM, Lai MS, Kennedy J, Uchiyama S, Yamaguchi T, Ikeda Y, Mrkobrada M. Statins and intracerebral hemor- rhage: collaborative systematic review and meta-analysis. Circulation. 2011;124:2233 2242. 163. Bedi US, Singh M, Singh PP, Bhuriya R, Bahekar A, Molnar J, Khosla S, Arora R. Effects of statins on progression of carotid atheroscle- rosis as measured by carotid intimal-medial thickness: a meta-anal- ysis of randomized controlled trials. J Cardiovasc Pharmacol Ther. 2010;15:268 273. 164. Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O Leary DH, Grobbee DE, Bots ML; METEOR Study Group. Effect of rosu- vastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297:1344 1353. 165. Smilde TJ, van Wissen S, Wollersheim H, Trip MD, Kastelein JJ, Stalenhoef AF. Effect of aggressive versus conventional lipid lower- ing on atherosclerosis progression in familial hypercholesterolae- mia (ASAP): a prospective, randomised, double-blind trial. Lancet. 2001;357:577 581. 166. Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vernalis MN. ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Circulation. 2002;106:2055 2060. 167. Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, Moore A, Lane T, Neradilek MB, Polissar N, Monick D, Lee C, Underhill H, Yuan C. MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging. 2011;4:977 986. 168. Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, U-King-Im JM, Li ZY, Walsh SR, Brown AP, Kirkpatrick PJ, Warburton EA, Hayes PD, Varty K, Boyle JR, Gaunt ME, Zalewski A, Gillard JH. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study: evaluation using ultrasmall superparamag- netic iron oxide-enhanced magnetic resonance imaging in carotid dis- ease. J Am Coll Cardiol. 2009;53:2039 2050. 169. Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(suppl 2):S1 S45. 170. De Caterina R, Scarano M, Marfisi R, Lucisano G, Palma F, Tatasciore A, Marchioli R. Cholesterol-lowering interventions and stroke: insights from a meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2010;55:198 211. 171. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8:1245 1255. 172. AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W. Niacin in patients with low HDL cholesterol levels receiv- ing intensive statin therapy. N Engl J Med. 2011;365:2255 2267. 173. Lavigne PM, Karas RH. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J Am Coll Cardiol. 2013;61:440 446. cebo-controlled trial in 25 673 high-risk patients of ER niacin/laropip- rant: trial design, pre-specified muscle, and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34:1279 1291. 175. Bezafibrate Infarction Prevention (BIP) Study. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coro- nary artery disease. Circulation. 2000;102:21 27. 176. Bloomfield Rubins H, Davenport J, Babikian V, Brass LM, Collins D, Wexler L, Wagner S, Papademetriou V, Rutan G, Robins SJ; VA-HIT Study Group. Reduction in stroke with gemfibrozil in men with coro- nary heart disease and low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Circulation. 2001;103:2828 2833. 177. ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, FriedewaldWT, Buse JB, Gerstein HC, Probstfield J, Grimm RH, Ismail-Beigi F, Bigger JT, Goff DC Jr, Cushman WC, Simons-Morton DG, Byington RP. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563 1574. 178. Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, Grobbee DE, Cass A, Chalmers J, Perkovic V. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375:1875 1884. 179. Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL, Sijbrands EJ, Trip MD, Stein EA, Gaudet D, Duivenvoorden R, Veltri EP, Marais AD, de Groot E; ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hyper- cholesterolemia. N Engl J Med. 2008;358:1431 1443. 180. Taylor AJ, Villines TC, Stanek EJ, Devine PJ, Griffen L, Miller M, Weissman NJ, Turco M. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009;361:2113 2122. 181. Cannon CP, Giugliano RP, Blazing MA, Harrington RA, Peterson JL, Sisk CM, Strony J, Musliner TA, McCabe CH, Veltri E, Braunwald E, Califf RM; IMPROVE-IT Investigators. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/ simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008;156:826 832. 182. Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM; American Heart Association. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47:296 308. 183. Appel LJ, Angell SY, Cobb LK, Limper HM, Nelson DE, Samet JM, Brownson RC. Population-wide sodium reduction: the bumpy road from evidence to policy. Ann Epidemiol. 2012;22:417 425. 184. Kamangar F, Karimi P. The state of nutritional epidemiology: why we are still unsure of what we should eat? Arch Iran Med. 2013;16:483 486. 185. He FJ, Nowson CA, MacGregor GA. Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. Lancet. 2006;367:320 326. 186. Joshipura KJ, Ascherio A, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, Hennekens CH, Spiegelman D, Willett WC. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA. 1999;282:1233 1239. 187. Cassidy A, Rimm EB, O Reilly EJ, Logroscino G, Kay C, Chiuve SE, Rexrode KM. Dietary flavonoids and risk of stroke in women. Stroke. 2012;43:946 951. 188. US Department of Agriculture and US Department of Health and Human Services. Dietary Guidelines for Americans 2010. 7th ed. Washington, DC: US Government Printing Office; December, 2010. E, Ruiz-GutierrezV, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Martinez-Gonzalez MA; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279 1290. 190. Perry IJ, Beevers DG. Salt intake and stroke: a possible direct effect. J Hum Hypertens. 1992;6:23 25. 191. He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA. 1999;282:2027 2034. 192. Nagata C, Takatsuka N, Shimizu N, Shimizu H. Sodium intake and risk of death from stroke in Japanese men and women. Stroke. 2004;35:1543 1547. 193. Li XY, Cai XL, Bian PD, Hu LR. High salt intake and stroke: meta-analy- sis of the epidemiologic evidence. CNS Neurosci Ther. 2012;18:691 701. 194. Strazzullo P, D Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ. 2009;339:b4567. 195. Ascherio A, Rimm EB, Hernan MA, Giovannucci EL, Kawachi I, Stampfer MJ, Willett WC. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men. Circulation. 1998;98:1198 1204. 196. Khaw KT, Barrett-Connor E. Dietary potassium and stroke-associ- ated mortality: a 12-year prospective population study. N Engl J Med. 1987;316:235 240. 197. D Elia L, Barba G, Cappuccio FP, Strazzullo P. Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies. J Am Coll Cardiol. 2011;57:1210 1219. 198. Larsson SC, Orsini N, Wolk A. Dietary potassium intake and risk of stroke: a dose-response meta-analysis of prospective studies. Stroke. 2011;42:2746 2750. 199. Chang HY, Hu YW, Yue CS, Wen YW, Yeh WT, Hsu LS, Tsai SY, Pan WH. Effect of potassium-enriched salt on cardiovascular mortality and medical expenses of elderly men. Am J Clin Nutr. 2006;83:1289 1296. 200. Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil- Smoller S, Kuller LH, LaCroix AZ, Langer RD, Lasser NL, Lewis CE, Limacher MC, Margolis KL, Mysiw WJ, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Schatz IJ, Snetselaar LG, Stevens VJ, Tinker LF, Trevisan M, Vitolins MZ, Anderson GL, Assaf AR, Bassford T, Beresford SA, Black HR, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Granek I, Greenland P, Hays J, Heber D, Heiss G, Hendrix SL, Hubbell FA, Johnson KC, Kotchen JM. Low-fat dietary pattern and risk of cardiovascular dis- ease: the Women s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295:655 666. 201. Tobian L, Lange JM, Ulm KM, Wold LJ, Iwai J. Potassium prevents death from strokes in hypertensive rats without lowering blood pressure. J Hypertens Suppl. 1984;2:S363 S366. 202. Johnson AG, Nguyen TV, Davis D. Blood pressure is linked to salt intake and modulated by the angiotensinogen gene in normotensive and hyper- tensive elderly subjects. J Hypertens. 2001;19:1053 1060. 203. MacGregor GA, Markandu ND, Sagnella GA, Singer DR, Cappuccio FP. Double-blind study of three sodium intakes and long-term effects of sodium restriction in essential hypertension. Lancet. 1989;2:1244 1247. 204. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet: DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3 10. 205. Vollmer WM, Sacks FM, Ard J, Appel LJ, Bray GA, Simons-Morton DG, Conlin PR, Svetkey LP, Erlinger TP, Moore TJ, Karanja N; DASH- Sodium Trial Collaborative Research Group Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial. Ann Intern Med. 2001;135:1019 1028. 206. Whelton PK, He J, Cutler JA, Brancati FL, Appel LJ, Follmann D, Klag MJ. Effects of oral potassium on blood pressure: meta-analysis of ran- domized controlled clinical trials. JAMA. 1997;277:1624 1632. 207. Morris RC Jr, Sebastian A, Forman A, Tanaka M, Schmidlin O. Normotensive salt sensitivity: effects of race and dietary potassium. Hypertension. 1999;33:18 23. 208. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N. A clinical trial of the effects of dietary patterns on blood pressure: DASH Collaborative Research Group. N Engl J Med. 1997;336:1117 1124. 209. Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller ER 3rd, Conlin PR, Erlinger TP, Rosner BA, Laranjo NM, Charleston J, McCarron P, Bishop LM; OmniHeart Collaborative Research Group. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005;294:2455 2464. 210. John JH, Ziebland S, Yudkin P, Roe LS, Neil HA; Oxford Fruit and Vegetable Study Group. Effects of fruit and vegetable consumption on plasma antioxidant concentrations and blood pressure: a randomised controlled trial. Lancet. 2002;359:1969 1974. 211. Institute of Medicine. Dietary Reference Intakes: Water, Potassium, Sodium, Chloride, and Sulfate. Washington, DC: National Academies Press; 2004. 212. Sauvaget C, Nagano J, Hayashi M, Yamada M. Animal protein, animal fat, and cholesterol intakes and risk of cerebral infarction mortality in the Adult Health Study. Stroke. 2004;35:1531 1537. 213. He K, Merchant A, Rimm EB, Rosner BA, Stampfer MJ, Willett WC, Ascherio A. Dietary fat intake and risk of stroke in male US healthcare professionals: 14 year prospective cohort study. BMJ. 2003;327:777 782. 214. Bernstein AM, Pan A, Rexrode KM, Stampfer M, Hu FB, Mozaffarian D, Willett WC. Dietary protein sources and the risk of stroke in men and women. Stroke. 2012;43:637 644. 215. Kaluza J, Wolk A, Larsson SC. Red meat consumption and risk of stroke: a meta-analysis of prospective studies. Stroke. 2012;43:2556 2560. 216. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm LH, Sorlie P, Yancy CW, Rosamond WD; American Heart Association Strategic Planning Task Force and Statistics Committee. Defining and setting national goals for cardiovascular health promo- tion and disease reduction: the American Heart Association s Strategic Impact Goal through 2020 and beyond. Circulation. 2010;121:586 613. 217. Kotchen TA, Cowley AW Jr, Frohlich ED. Salt in health and disease: a delicate balance. N Engl J Med. 2013;368:1229 1237. 218. Go AS, Bauman MA, Coleman King SM, Fonarow GC, Lawrence W, Williams KA, Sanchez E; American Heart Association; American College of Cardiology; Centers for Disease Control and Prevention An effective approach to high blood pressure control: a science advi- sory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014;63:878 885. 219. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206 1252. 220. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507 520. 221. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. Meschia et al Guidelines for the Primary Prevention of Stroke 3813 The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560 2572. 222. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903 1913. 223. Fields LE, Burt VL, Cutler JA, Hughes J, Roccella EJ, Sorlie P. The bur- den of adult hypertension in the United States 1999 to 2000: a rising tide. Hypertension. 2004;44:398 404. 224. Egan BM, Zhao Y, Axon RN. US trends in prevalence, aware- ness, treatment, and control of hypertension, 1988 2008. JAMA. 2010;303:2043 2050. 225. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in chil- dren, and adolescents. Pediatrics. 2004;114(suppl 4th Report):555 576. 226. Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, Horan MJ, Labarthe D. Prevalence of hypertension in the US adult popula- tion: results from the Third National Health and Nutrition Examination Survey, 1988 1991. Hypertension. 1995;25:305 313. 227. Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, D Agostino RB, Levy D. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study. JAMA. 2002;287:1003 1010. 228. Whelton PK, He J, Appel LJ, Cutler JA, Havas S, Kotchen TA, Roccella EJ, Stout R, Vallbona C, Winston MC, Karimbakas J; National High Blood Pressure Education Program Coordinating Committee. Primary prevention of hypertension: clinical and public health advisory from the National High Blood Pressure Education Program. JAMA. 2002;288:1882 1888. 229. Sipahi I, Swaminathan A, Natesan V, Debanne SM, Simon DI, Fang JC. Effect of antihypertensive therapy on incident stroke in cohorts with pre- hypertensive blood pressure levels: a meta-analysis of randomized con- trolled trials. Stroke. 2012;43:432 440. 230. Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH, Weiss NS. Health outcomes associated with various antihyperten- sive therapies used as first-line agents: a network meta-analysis. JAMA. 2003;289:2534 2544. 231. Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev. 2012;8:CD006742. 232. Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA. Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA. 2011;305:913 922. 233. McAlister F; Renin Angiotensin System Modulator Meta-Analysis Investigators. Angiotensin-converting enzyme inhibitors or angioten- sin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta-analysis of randomized trials. Eur Heart J. 2012;33:505 514. 234. Turnbull F; Blood Pressure Lowering Treatment Trialists Collaboration. Effects of different blood-pressure-lowering regimens on major car- diovascular events: results of prospectively-designed overviews of ran- domised trials. Lancet. 2003;362:1527 1535. 235. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 ran- domised trials in the context of expectations from prospective epidemio- logical studies. BMJ. 2009;338:b1665. 236. Wright JM, Musini VM. First-line drugs for hypertension. Cochrane Database Syst Rev. 2009:CD001841. 237. Fretheim A, Odgaard-Jensen J, Brors O, Madsen S, Njolstad I, Norheim OF, Svilaas A, Kristiansen IS, Thurmer H, Flottorp S. Comparative effectiveness of antihypertensive medication for primary prevention of cardiovascular disease: systematic review and multiple treatments meta- analysis. BMC Med. 2012;10:33. 238. Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Mbewu A, Opie LH. Beta-blockers for hypertension. Cochrane Database Syst Rev. 2012;8:CD002003. 239. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group; Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981 2997. 240. Ogihara T, Matsuzaki M, Umemoto S, Rakugi H, Matsuoka H, Shimada K, Higaki J, Ito S, Kamiya A, Suzuki H, OhashiY, Shimamoto K, Saruta T; Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial Group. Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial. Hypertens Res. 2012;35:441 448. 241. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367:2204 2213. 242. Black HR, Elliott WJ, Neaton JD, Grandits G, Grambsch P, Grimm RH Jr, Hansson L, LacouciereY, Muller J, Sleight P, Weber MA, White WB, Williams G, Wittes J, Zanchetti A, Fakouhi TD, Anders RJ. Baseline characteristics and early blood pressure control in the CONVINCE Trial. Hypertension. 2001;37:12 18. 243. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr,Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM; ALLHAT Collaborative Research Group. Success and pre- dictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4:393 404. 244. Matsuzaki M, Ogihara T, Umemoto S, Rakugi H, Matsuoka H, Shimada K,Abe K, Suzuki N, Eto T, Higaki J, Ito S, KamiyaA, Kikuchi K, Suzuki H, Tei C, Ohashi Y, Saruta T; Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial Group. Prevention of cardiovascu- lar events with calcium channel blocker-based combination therapies in patients with hypertension: a randomized controlled trial. J Hypertens. 2011;29:1649 1659. 245. Lee M, Saver JL, Hong KS, Hao Q, Ovbiagele B. Does achieving an intensive versus usual blood pressure level prevent stroke? Ann Neurol. 2012;71:133 140. 246. Barzilay JI, Howard AG, Evans GW, Fleg JL, Cohen RM, Booth GL, Kimel AR, Pedley CF, Cushman WC. Intensive blood pressure treatment does not improve cardiovascular outcomes in centrally obese hyper- tensive individuals with diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial. Diabetes Care. 2012;35:1401 1405. 247. ACCORD Study Group. Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of inten- sive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575 1585. 248. Reboldi G, Gentile G, Angeli F, Ambrosio G, Mancia G, Verdecchia P. Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients. J Hypertens. 2011;29:1253 1269. 249. Okin PM, Hille DA, Kjeldsen SE, Dahlof B, Devereux RB. Impact of lower achieved blood pressure on outcomes in hypertensive patients. J Hypertens. 2012;30:802 810. 250. Sherva R, Ford CE, Eckfeldt JH, Davis BR, Boerwinkle E, Arnett DK. Pharmacogenetic effect of the stromelysin (MMP3) polymorphism on stroke risk in relation to antihypertensive treatment: the genetics of hypertension associated treatment study. Stroke. 2011;42:330 335. 251. Lynch AI, Boerwinkle E, Davis BR, Ford CE, Eckfeldt JH, Leiendecker- Foster C, Arnett DK. Antihypertensive pharmacogenetic effect of fibrin- ogen-beta variant -455G>A on cardiovascular disease, end-stage renal disease, and mortality: the GenHAT study. Pharmacogenet Genomics. 2009;19:415 421. 252. Rothwell PM, Howard SC, Dolan E, O Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010;375:895 905. 253. WebbAJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive- drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet. 2010;375:906 915. 254. Rothwell PM, Howard SC, Dolan E, O Brien E, Dobson JE, Dahlof B, Poulter NR, Sever PS; ASCOT-BPLA and MRC Trial Investigators. Effects of beta blockers and calcium-channel blockers on within-indi- vidual variability in blood pressure and risk of stroke. Lancet Neurol. 2010;9:469 480. 255. Fagard RH, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens. 2009;23:645 653. 256. Kario K, Pickering TG, Matsuo T, Hoshide S, Schwartz JE, Shimada K. Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives. Hypertension. 2001;38:852 857. 257. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887 1898. 258. Prevention of stroke by antihypertensive drug treatment in older per- sons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP): SHEP Cooperative Research Group. JAMA. 1991;265:3255 3264. 259. Flack JM, Sica DA, Bakris G, Brown AL, Ferdinand KC, Grimm RH Jr, Hall WD, Jones WE, Kountz DS, Lea JP, Nasser S, Nesbitt SD, Saunders E, Scisney-Matlock M, Jamerson KA; International Society on Hypertension in Blacks. Management of high blood pressure in blacks: an update of the International Society on Hypertension in Blacks consen- sus statement. Hypertension. 2010;56:780 800. 260. Wald DS, Wald NJ. Implementation of a simple age-based strategy in the prevention of cardiovascular disease: the Polypill approach. J Eval Clin Pract. 2012;18:612 615. 261. Uhlig K, Patel K, Ip S, Kitsios GD, Balk EM. Self-measured blood pres- sure monitoring in the management of hypertension: a systematic review and meta-analysis. Ann Intern Med. 2013;159:185 194. 262. Centers for Disease Control and Prevention. Chronic disease prevention and health promotion, obesity: halting the epidemic by making health easier at a glance 2011. http://www.cdc.gov/chronicdisease/resources/ publications/AAG/obesity.htm. Accessed February 27, 2013. 263. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of Obesity in the United States 2009 2010: NCHS Data Brief, No. 82. Hyattsville, MD: National Center for Health Statistics; 2012. 264. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999 2010. JAMA. 2012;307:491 497. 265. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999 2010. JAMA. 2012;307:483 490. 266. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report: National Institutes of Health. Obes Res. 1998;6(suppl 2):51S 209S. 267. Wildman RP, McGinn AP, Lin J, Wang D, Muntner P, Cohen HW, Reynolds K, Fonseca V, Sowers MR. Cardiovascular disease risk of abdominal obesity vs. metabolic abnormalities. Obesity (Silver Spring). 2011;19:853 860. 268. de Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J. 2007;28:850 856. 269. Suk SH, Sacco RL, Boden-Albala B, Cheun JF, Pittman JG, Elkind MS, Paik MC; Northern Manhattan Stroke Study. Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study. Stroke. 2003;34:1586 1592. 270. Walker SP, Rimm EB, Ascherio A, Kawachi I, Stampfer MJ, Willett WC. Body size and fat distribution as predictors of stroke among US men. Am J Epidemiol. 1996;144:1143 1150. 271. Kizer JR, Biggs ML, Ix JH, Mukamal KJ, Zieman SJ, de Boer IH, Mozaffarian D, Barzilay JI, Strotmeyer ES, Luchsinger JA, Elkind MS, Longstreth WT Jr, Kuller LH, Siscovick DS. Measures of adiposity and future risk of ischemic stroke and coronary heart disease in older men and women. Am J Epidemiol. 2011;173:10 25. 272. Toss F, Wiklund P, Franks PW, Eriksson M, Gustafson Y, Hallmans G, Nordstrom P, Nordstrom A. Abdominal and gynoid adiposity and the risk of stroke. Int J Obes (Lond). 2011;35:1427 1432. 273. Prospective Studies Collaboration; Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body- mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083 1096. 274. Strazzullo P, D Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. Excess body weight and incidence of stroke: meta-analysis of prospec- tive studies with 2 million participants. Stroke. 2010;41:e418 e426. 275. Wang C, Liu Y, Yang Q, Dai X, Wu S, Wang W, Ji X, Li L, Fang X. Body mass index and risk of total and type-specific stroke in Chinese adults: results from a longitudinal study in China. Int J Stroke. 2013;8:245 250. 276. Yatsuya H, Toyoshima H,Yamagishi K, Tamakoshi K, Taguri M, Harada A, Ohashi Y, Kita Y, Naito Y, Yamada M, Tanabe N, Iso H, Ueshima H; Japan Arteriosclerosis Longitudinal Study (JALS) Group. Body mass index and risk of stroke and myocardial infarction in a relatively lean population: meta-analysis of 16 Japanese cohorts using individual data. Circ Cardiovasc Qual Outcomes. 2010;3:498 505. 277. Yatsuya H, Folsom AR, Yamagishi K, North KE, Brancati FL, Stevens J; Atherosclerosis Risk in Communities Study Investigators. Race- and sex-specific associations of obesity measures with ischemic stroke inci- dence in the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2010;41:417 425. 278. Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial: a prospective controlled intervention study of bariatric sur- gery. J Intern Med. 2013;273:219 234. 279. Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R, Hu G. Lifestyle factors and antihypertensive treatment on the risks of ischemic and hemorrhagic stroke. Hypertension. 2012;60:906 912. 280. Caterson ID, Finer N, Coutinho W, Van Gaal LF, Maggioni AP, Torp- Pedersen C, Sharma AM, Legler UF, Shepherd GM, Rode RA, Perdok RJ, Renz CL, James WP; SCOUT Investigators. Maintained inten- tional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Diabetes Obes Metab. 2012;14:523 530. 281. Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JM. Influence of weight reduction on blood pressure: a meta-analysis of randomized con- trolled trials. Hypertension. 2003;42:878 884. 282. US Preventive Services Task Force. Screening for and management of obesity in adults, topic page. http://www.uspreventiveservicestaskforce. org/uspsobes.htm. Accessed December 7, 2013. 283. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States, 2011. Atlanta, GA, US Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed October 4, 2014. 284. Banerjee C, Moon YP, Paik MC, Rundek T, Mora-McLaughlin C, Vieira JR, Sacco RL, Elkind MS. Duration of diabetes and risk of ischemic stroke: the Northern Manhattan Study. Stroke. 2012;43:1212 1217. 285. Sui X, Lavie CJ, Hooker SP, Lee DC, Colabianchi N, Lee CD, Blair SN. A prospective study of fasting plasma glucose and risk of stroke in asymptomatic men. Mayo Clin Proc. 2011;86:1042 1049. 286. Kissela BM, Khoury J, Kleindorfer D, Woo D, Schneider A, Alwell K, Miller R, Ewing I, Moomaw CJ, Szaflarski JP, Gebel J, Shukla R, Broderick JP. Epidemiology of ischemic stroke in patients with diabetes: the greater Cincinnati/Northern Kentucky Stroke Study. Diabetes Care. 2005;28:355 359. 287. Boden-Albala B, Cammack S, Chong J, Wang C, Wright C, Rundek T, Elkind MS, Paik MC, Sacco RL. Diabetes, fasting glucose levels, and risk of ischemic stroke and vascular events: findings from the Northern Manhattan Study (NOMAS). Diabetes Care. 2008;31:1132 1137. 288. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a mul- tifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580 591. 289. Anselmino M, Malmberg K, Ohrvik J, Ryden L; Euro Heart Survey Investigators. Evidence-based medication and revascularization: power- ful tools in the management of patients with diabetes and coronary artery disease: a report from the Euro Heart Survey on diabetes and the heart. Eur J Cardiovasc Prev Rehabil. 2008;15:216 223. 290. Effect of intensive blood-glucose control with metformin on compli- cations in overweight patients with type 2 diabetes (UKPDS 34): UK ProspectiveDiabetesStudy(UKPDS)Group.Lancet.1998;352:854 865. 291. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577 1589. 292. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lower- ing in type 2 diabetes. N Engl J Med. 2008;358:2545 2559. 293. ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, RodgersA, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560 2572. Meschia et al Guidelines for the Primary Prevention of Stroke 3815 294. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129 139. 295. Gray CS, Hildreth AJ, Sandercock PA, O Connell JE, Johnston DE, Cartlidge NE, Bamford JM, James OF, Alberti KG; GIST Trialists. Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol. 2007;6:397 406. BV, Kirkman MS, Kosiborod M, Reaven P, Sherwin RS;American Diabetes Association; American College of Cardiology Foundation; American Heart Association. Intensive glycemic control and the prevention of cardiovas- cular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a sci- entific statement of the American College of Cardiology Foundation and the American Heart Association. Circulation. 2009;119:351 357. 297. Implementation of treatment protocols in the Diabetes Control and Complications Trial. Diabetes Care. 1995;18:361 376. 298. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC) Study Research Group. Intensive diabetes treatment and car- diovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643 2653. 299. Zhang C, ZhouYH, Xu CL, Chi FL, Ju HN. Efficacy of intensive control of glucose in stroke prevention: a meta-analysis of data from 59197 par- ticipants in 9 randomized controlled trials. PLoS One. 2013;8:e54465. 300. Tuomilehto J, Rastenyte D. Diabetes and glucose intolerance as risk fac- tors for stroke. J Cardiovasc Risk. 1999;6:241 249. 301. Tight blood pressure control and risk of macrovascular and microvas- cular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317:703 713. 302. Curb JD, Pressel SL, Cutler JA, Savage PJ, Applegate WB, Black H, Camel G, Davis BR, Frost PH, Gonzalez N, Guthrie G, Oberman A, Rutan GH, Stamler J. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension: Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA. 1996;276:1886 1892. 303. Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359:1565 1576. 304. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study, and MICRO- HOPE substudy: Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355:253 259. 305. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H; LIFE Study Group. 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. 306. Wachtell K, Hornestam B, Lehto M, Slotwiner DJ, Gerdts E, Olsen MH, Aurup P, Dahlof B, Ibsen H, Julius S, Kjeldsen SE, Lindholm LH, Nieminen MS, Rokkedal J, Devereux RB. Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol. 2005;45:705 711. 307. Patel A, ADVANCE Collaborative Group, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Rodgers A, Williams B. Effects of a fixed com- bination of perindopril and indapamide on macrovascular and microvas- cular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829 840. 308. Ostergren J, Poulter NR, Sever PS, Dahlof B, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O Brien E: ASCOT Investigators. The Anglo- Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes. J Hypertens. 2008;26:2103 2111. 309. Jamerson K, Weber MA, Bakris GL, Dahlof B, Pitt B, Shi V, Hester A, Gupte J, Gatlin M, Velazquez EJ: ACCOMPLISH Trial Investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359:2417 2428. 310. Bangalore S, Kumar S, Lobach I, Messerli FH. Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observa- tions from traditional and bayesian random-effects meta-analyses of ran- domized trials. Circulation. 2011;123:2799 2810, 9 p following 2810. 311. Goldberg RB, Mellies MJ, Sacks FM, Moye LA, Howard BV, Howard WJ, Davis BR, Cole TG, Pfeffer MA, Braunwald E. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intol- erant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial: the Care Investigators. Circulation. 1998;98:2513 2519. 312. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O Brien E, Ostergren J: ASCOT Investigators. 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 LoweringArm (ASCOT-LLA): a multicen- tre randomised controlled trial. Lancet. 2003;361:1149 1158. 313. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk indi- viduals: a randomised placebo-controlled trial. Lancet. 2002;360:7 22. 314. Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol- lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005 2016. 315. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH; CARDS Investigators. 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. 316. Shepherd J, Barter P, Carmena R, Deedwania P, Fruchart JC, Haffner S, Hsia J, Breazna A, LaRosa J, Grundy S, Waters D. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care. 2006;29:1220 1226. 317. Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C. 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. 318. Rubins HB, Robins SJ, Collins D, Nelson DB, Elam MB, Schaefer EJ, Faas FH, Anderson JW. Diabetes, plasma insulin, and cardiovascular dis- ease: subgroup analysis from the Department of Veterans Affairs High- Density Lipoprotein Intervention Trial (VA-HIT). Arch Intern Med. 2002;162:2597 2604. 319. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesaniemi YA, Sullivan D, Hunt D, Colman P, d Emden M, Whiting M, Ehnholm C, Laakso M: FIELD Study Investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabe- tes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849 1861. 320. ZhouYH,Ye XF,Yu FF, Zhang X, QinYY, Lu J, He J. Lipid management in the prevention of stroke: a meta-analysis of fibrates for stroke preven- tion. BMC Neurol. 2013;13:1. 321. Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Sugiyama S, Saito Y; Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300:2134 2141. 322. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocar- dial infarction, and stroke in high risk patients. BMJ. 2002;324:71 86. 323. Butalia S, Leung AA, Ghali WA, Rabi DM. Aspirin effect on the inci- dence of major adverse cardiovascular events in patients with diabetes mellitus: a systematic review and meta-analysis. Cardiovasc Diabetol. 2011;10:25. 324. Kobzar G, Mardla V, Samel N. Short-term exposure of platelets to glu- cose impairs inhibition of platelet aggregation by cyclooxygenase inhibi- tors. Platelets. 2011;22:338 344. 325. Simpson SH, Gamble JM, Mereu L, Chambers T. Effect of aspirin dose on mortality and cardiovascular events in people with diabetes: a meta- analysis. J Gen Intern Med. 2011;26:1336 1344. 326. Manolio TA, Kronmal RA, Burke GL, O Leary DH, Price TR. Short- term predictors of incident stroke in older adults: the Cardiovascular Health Study. Stroke. 1996;27:1479 1486. 327. Rodriguez BL, D Agostino R, Abbott RD, Kagan A, Burchfiel CM, Yano K, Ross GW, Silbershatz H, Higgins MW, Popper J, Wolf PA, Curb JD. Risk of hospitalized stroke in men enrolled in the Honolulu Heart Program and the Framingham Study: A comparison of incidence and risk factor effects. Stroke. 2002;33:230 236. 328. Bhat VM, Cole JW, Sorkin JD, Wozniak MA, Malarcher AM, Giles WH, Stern BJ, Kittner SJ. Dose-response relationship between ciga- rette smoking and risk of ischemic stroke in young women. Stroke. 2008;39:2439 2443. 329. Feigin V, Parag V, Lawes CM, Rodgers A, Suh I, Woodward M, Jamrozik K, Ueshima H; Asia Pacific Cohort Studies Collaboration. Smoking and elevated blood pressure are the most important risk factors for subarach- noid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants. Stroke. 2005;36:1360 1365. 330. Feigin VL, Rinkel GJ, Lawes CM, Algra A, Bennett DA, van Gijn J, Anderson CS. Risk factors for subarachnoid hemorrhage: an updated sys- tematic review of epidemiological studies. Stroke. 2005;36:2773 2780. 331. Kurth T, Kase CS, Berger K, Gaziano JM, Cook NR, Buring JE. Smoking and risk of hemorrhagic stroke in women. Stroke. 2003;34:2792 2795. 332. Kurth T, Kase CS, Berger K, Schaeffner ES, Buring JE, Gaziano JM. Smoking and the risk of hemorrhagic stroke in men. Stroke. 2003;34:1151 1155. 333. Feldmann E, Broderick JP, Kernan WN, Viscoli CM, Brass LM, Brott T, Morgenstern LB, Wilterdink JL, Horwitz RI. Major risk fac- tors for intracerebral hemorrhage in the young are modifiable. Stroke. 2005;36:1881 1885. 334. Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracere- bral hemorrhage in the general population: a systematic review. Stroke. 2003;34:2060 2065. 335. Shinton R, Beevers G. Meta-analysis of relation between cigarette smok- ing and stroke. BMJ. 1989;298:789 794. 336. ThriftAG, McNeil JJ, Donnan GA. The risk of intracerebral haemorrhage with smoking: the Melbourne Risk Factor Study Group. Cerebrovasc Dis. 1999;9:34 39. 337. Thun MJ, Apicella LF, Henley SJ. Smoking vs other risk factors as the cause of smoking-attributable deaths: confounding in the courtroom. JAMA. 2000;284:706 712. 338. Centers for Disease Control and Prevention (CDC). Smoking-attributable mortality, years of potential life lost, and productivity losses United States, 2000 2004. MMWR Morb MortalWkly Rep. 2008;57:1226 1228. 339. Nakamura K, Barzi F, Lam TH, Huxley R, Feigin VL, Ueshima H, Woo J, Gu D, Ohkubo T, Lawes CM, Suh I, Woodward M; Asia Pacific Cohort Studies Investigators. Cigarette smoking, systolic blood pres- sure, and cardiovascular diseases in the Asia-Pacific region. Stroke. 2008;39:1694 1702. 340. Ischaemic stroke and combined oral contraceptives: results of an inter- national, multicentre, case-control study: WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1996;348:498 505. 341. Haemorrhagic stroke, overall stroke risk, and combined oral contracep- tives: results of an international, multicentre, case-control study: WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1996;348:505 510. 342. US Department of Health, and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2006. 343. Barnoya J, Glantz SA. Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation. 2005;111:2684 2698. 344. Bonita R, Duncan J, Truelsen T, Jackson RT, Beaglehole R. Passive smoking as well as active smoking increases the risk of acute stroke. Tob Control. 1999;8:156 160. 345. He Y, Lam TH, Jiang B, Wang J, Sai X, Fan L, Li X, Qin Y, Hu FB. Passive smoking and risk of peripheral arterial disease and isch- emic stroke in Chinese women who never smoked. Circulation. 2008;118:1535 1540. 346. Iribarren C, Darbinian J, Klatsky AL, Friedman GD. Cohort study of exposure to environmental tobacco smoke and risk of first ischemic stroke and transient ischemic attack. Neuroepidemiology. 2004;23:38 44. 347. Qureshi AI, Suri MF, Kirmani JF, Divani AA. Cigarette smok- ing among spouses: another risk factor for stroke in women. Stroke. 2005;36:e74 e76. 348. You RX, Thrift AG, McNeil JJ, Davis SM, Donnan GA. Ischemic stroke risk and passive exposure to spouses' cigarette smoking: Melbourne Stroke RiskFactorStudy(MERFS)Group.AmJPublicHealth.1999;89:572 575. 349. Zhang X, Shu XO, Yang G, Li HL, Xiang YB, Gao YT, Li Q, Zheng W. Association of passive smoking by husbands with prevalence of stroke among Chinese women nonsmokers. Am J Epidemiol. 2005;161:213 218. 350. Whincup PH, Gilg JA, Emberson JR, Jarvis MJ, Feyerabend C, Bryant A, Walker M, Cook DG. Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement. BMJ. 2004;329:200 205. 351. Howard G, Thun MJ. Why is environmental tobacco smoke more strongly associated with coronary heart disease than expected? A review of potential biases and experimental data. Environ Health Perspect. 1999;107(suppl 6):853 858. 352. Herman PM, Walsh ME. Hospital admissions for acute myocardial infarc- tion, angina, stroke, and asthma after implementation ofArizona s compre- hensive statewide smoking ban. Am J Public Health. 2011;101:491 496. 353. Juster HR, Loomis BR, Hinman TM, Farrelly MC, Hyland A, Bauer UE, Birkhead GS. Declines in hospital admissions for acute myocardial infarction in New York state after implementation of a comprehensive smoking ban. Am J Public Health. 2007;97:2035 2039. 354. Burns DM. Epidemiology of smoking-induced cardiovascular disease. Prog Cardiovasc Dis. 2003;46:11 29. 355. Kool MJ, Hoeks AP, Struijker Boudier HA, Reneman RS, Van Bortel LM. Short- and long-term effects of smoking on arterial wall properties in habitual smokers. J Am Coll Cardiol. 1993;22:1881 1886. 356. Silvestrini M, Troisi E, Matteis M, Cupini LM, Bernardi G. Effect of smoking on cerebrovascular reactivity. J Cereb Blood Flow Metab. 1996;16:746 749. 357. Howard G, Wagenknecht LE, Burke GL, Diez-Roux A, Evans GW, McGovern P, Nieto FJ, Tell GS. Cigarette smoking and progression of atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. JAMA. 1998;279:119 124. 358. Karttunen V, Alfthan G, Hiltunen L, Rasi V, Kervinen K, Kesaniemi YA, Hillbom M. Risk factors for cryptogenic ischaemic stroke. Eur J Neurol. 2002;9:625 632. 359. Ohira T, Shahar E, Chambless LE, RosamondWD, Mosley TH Jr, Folsom AR. Risk factors for ischemic stroke subtypes: the Atherosclerosis Risk in Communities study. Stroke. 2006;37:2493 2498. 360. Fagerstrom K. The epidemiology of smoking: health consequences and benefits of cessation. Drugs. 2002;62(suppl 2):1 9. 361. RobbinsAS, Manson JE, Lee IM, Satterfield S, Hennekens CH. Cigarette smoking and stroke in a cohort of U.S. male physicians. Ann Intern Med. 1994;120:458 462. 362. Song YM, Cho HJ. Risk of stroke and myocardial infarction after reduc- tion or cessation of cigarette smoking: a cohort study in Korean men. Stroke. 2008;39:2432 2438. of Smoking: A Report of the Surgeon General. Washington, DC: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2004. 364. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2008:CD006103. apy for smoking cessation. Cochrane Database Syst Rev. 2008:CD000146. 366. Fiore MC, Jean CR, Baker TB, Bailey WC, Benowitz N, Curry SJ, Dorfman SF, Froelicher ES, Goldstein MG, Healton CG, Henderson PN, Heyman RB, Koh HK, Kottke TE, Lando HA, Mecklenburg RE, Mermeistein RJ, Mullen PD, Orleans CT, Robinson L, Stitzer ML, Tommasello AC, Villejo L, Wewers ME. Treating Tobacco Use and Dependence: 2008 Update. Quick Reference Guide for Clinicians. Rockville, MD: US Department of Health and Human Services, Public Health Service. April 2009. 367. US Preventive Services Task Force. Counseling, and interventions to prevent tobacco use, and tobacco-caused disease in adults, and pregnant women: U.S. Preventive Services Task Force reaffirmation recommenda- tion statement. Ann Intern Med. 2009;150:551 555. of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: a systematic review and multiple treatment meta-analysis. Ann Med. 2012;44:588 597. Meschia et al Guidelines for the Primary Prevention of Stroke 3817 369. Bolin K, Wilson K, Benhaddi H, de Nigris E, Marbaix S, Mork AC, Aubin HJ. Cost-effectiveness of varenicline compared with nicotine patches for smoking cessation: results from four European countries. Eur J Public Health. 2009;19:650 654. 370. Kannel WB, Benjamin EJ. Status of the epidemiology of atrial fibrilla- tion. Med Clin North Am. 2008;92:17 40, ix. 371. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke. 1991;22:983 988. 372. Stroke Risk in Atrial Fibrillation Working Group. Independent predic- tors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69:546 554. 373. Stroke Risk in Atrial Fibrillation Working Group. Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke. 2008;39:1901 1910. 374. Benjamin EJ, Wolf PA, D Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98:946 952. 375. Marini C, De Santis F, Sacco S, Russo T, Olivieri L, Totaro R, Carolei A. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke. 2005;36:1115 1119. 376. Fitzmaurice DA, Hobbs FD, Jowett S, Mant J, Murray ET, Holder R, Raftery JP, Bryan S, Davies M, Lip GY, Allan TF. Screening versus rou- tine practice in detection of atrial fibrillation in patients aged 65 or over: cluster randomised controlled trial. BMJ. 2007;335:383. 377. Hobbs FD, Fitzmaurice DA, Mant J, Murray E, Jowett S, Bryan S, Raftery J, Davies M, Lip G. A randomised controlled trial and cost- effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over: the SAFE study. Health Technol Assess. 2005;9:iii-iv, ix-x, 1 74. 378. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285:2864 2870. 379. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest. 2010;137:263 272. 380. You JJ, Singer DE, Howard PA, Lane DA, Eckman MH, Fang MC, Hylek EM, Schulman S, GoAS, Hughes M, Spencer FA, Manning WJ, Halperin JL, Lip GY; American College of Chest Physicians. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest. 2012;141:e531S 575S. 381. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093 1100. 382. Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. Performance of the HEMORR(2)HAGES,ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) study. J Am Coll Cardiol. 2012;60:861 867. 383. Taillandier S, Olesen JB, Clementy N, Lagrenade I, Babuty D, Lip GY, Fauchier L. Prognosis in patients with atrial fibrillation and CHA2DS2- VASc Score=0 in a community-based cohort study. J Cardiovasc Electrophysiol. 2012;23:708 713. 384. Fang MC, Go AS, Chang Y, Borowsky LH, Pomernacki NK, Udaltsova N, Singer DE. A new risk scheme to predict warfarin-associated hem- orrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol. 2011;58:395 401. 385. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857 867. 386. Andersen KK, Olsen TS. Reduced poststroke mortality in patients with stroke and atrial fibrillation treated with anticoagulants: results from a Danish quality-control registry of 22,179 patients with ischemic stroke. Stroke. 2007;38:259 263. 387. Hylek EM, Go AS, ChangY, Jensvold NG, Henault LE, Selby JV, Singer DE. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med. 2003;349:1019 1026. 388. O Donnell M, OczkowskiW, Fang J, Kearon C, Silva J, Bradley C, Guyatt G, Gould L, D Uva C, Kapral M, Silver F; Investigators of the Registry of the Canadian Stroke Network. Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study. Lancet Neurol. 2006;5:749 754. 389. Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, Murray E; BAFTA Investigators; Midland Research Practices Network (MidReC). 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 con- trolled trial. Lancet. 2007;370:493 503. 390. Furie KL, Goldstein LB, Albers GW, Khatri P, Neyens R, Turakhia MP, Turan TN, Wood KA; on behalf of the American Heart Association Stroke Council; Council on Quality of Care and Outcomes Research; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Council on Peripheral Vascular Disease. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advi- sory for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke. 2012;43:3442 3453. 391. Hohnloser SH, Oldgren J, Yang S, Wallentin L, Ezekowitz M, Reilly P, Eikelboom J, Brueckmann M, Yusuf S, Connolly SJ. Myocardial ischemic events in patients with atrial fibrillation treated with dabiga- tran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012;125:669 676. 392. Connolly SJ, Ezekowitz MD,Yusuf S, Eikelboom J, Oldgren J, ParekhA, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfa- rin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139 1151. 393. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized con- trolled trials. Arch Intern Med. 2012;172:397 402. 394. Hori M, Connolly SJ, Ezekowitz MD, Reilly PA, Yusuf S, Wallentin L; RE-LY Investigators. Efficacy and safety of dabigatran vs. warfarin in patients with atrial fibrillation: sub-analysis in Japanese population in RE-LY trial. Circ J. 2011;75:800 805. 395. Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, Kamensky G, Reilly PA, Yang S, Yusuf S, Wallentin L, Connolly SJ; RE-LY Investigators. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med. 2011;155:660 667, W204. 396. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, Yang S, Alings M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J, Yusuf S. Risk of bleed- ing with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123:2363 2372. 397. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883 891. 398. Hankey GJ, Patel MR, Stevens SR, Becker RC, Breithardt G, Carolei A, Diener HC, Donnan GA, Halperin JL, Mahaffey KW, Mas JL, Massaro A, Norrving B, Nessel CC, Paolini JF, Roine RO, Singer DE, Wong L, Califf RM, Fox KA, Hacke W; ROCKET AF Steering Committee Investigators. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012;11:315 322. 399. Fox KA, Piccini JP, Wojdyla D, Becker RC, Halperin JL, Nessel CC, Paolini JF, Hankey GJ, Mahaffey KW, Patel MR, Singer DE, Califf RM. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moder- ate renal impairment. Eur Heart J. 2011;32:2387 2394. 400. Fleming TR, Emerson SS. Evaluating rivaroxaban for nonvalvu- lar atrial fibrillation: regulatory considerations. N Engl J Med. 2011;365:1557 1559. 401. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, Flaker G, Avezum A, Hohnloser SH, Diaz R, Talajic M, Zhu J, Pais P, Budaj A, Parkhomenko A, Jansky P, Commerford P, Tan RS, Sim KH, Lewis BS,Van Mieghem W, Lip GY, Kim JH, Lanas-Zanetti F, Gonzalez- Hermosillo A, Dans AL, Munawar M, O Donnell M, Lawrence J, Lewis G, Afzal R, Yusuf S; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364:806 817. 402. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrilla- tion. N Engl J Med. 2011;365:981 992. 403. Diener HC, Eikelboom J, Connolly SJ, Joyner CD, Hart RG, Lip GY, O Donnell M, Hohnloser SH, Hankey GJ, Shestakovska O, Yusuf S; AVERROES Steering Committee and Investigators. Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial. Lancet Neurol. 2012;11:225 231. 404. Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB, Wallentin L, Alings M, Goto S, Lewis BS, Rosenqvist M, Hanna M, Mohan P, Alexander JH, Diener HC; ARISTOTLE Committees and Investigators. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol. 2012;11:503 511. 405. Hohnloser SH, Hijazi Z, Thomas L, Alexander JH, Amerena J, Hanna M, Keltai M, Lanas F, Lopes RD, Lopez-Sendon J, Granger CB, Wallentin L. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from theARISTOTLE trial. Eur Heart J. 2012;33:2821 2830. 406. Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, Wang PJ, Turakhia MP. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med. 2011;154:1 11. 407. Kamel H, Johnston SC, Easton JD, Kim AS. Cost-effectiveness of dabi- gatran compared with warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke. 2012;43:881 883. 408. Kansal AR, Sorensen SV, Gani R, Robinson P, Pan F, Plumb JM, Cowie MR. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation. Heart. 2012;98:573 578. 409. Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophy- laxis in atrial fibrillation. Circulation. 2011;123:2562 2570. 410. Krauel K, Hackbarth C, Furll B, Greinacher A. Heparin-induced throm- bocytopenia: in vitro studies on the interaction of dabigatran, rivaroxa- ban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies. Blood. 2012;119:1248 1255. 411. Chatterjee S, Sardar P, Biondi-Zoccai G, Kumbhani DJ. New oral anticoagulants and the risk of intracranial hemorrhage: traditional and bayesian meta-analysis and mixed treatment comparison of random- ized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol. 2013;70:1486 1490. 412. Kaatz S, Kouides PA, Garcia DA, Spyropolous AC, Crowther M, Douketis JD, Chan AK, James A, Moll S, Ortel TL, Van Cott EM, Ansell J. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(suppl 1):S141 S145. 413. Dowlatshahi D, Butcher KS, Asdaghi N, Nahirniak S, Bernbaum ML, Giulivi A, Wasserman JK, Poon MC, Coutts SB; Canadian PCC Registry (CanPro) Investigators. Poor prognosis in warfarin-associ- ated intracranial hemorrhage despite anticoagulation reversal. Stroke. 2012;43:1812 1817. 414. 