Declining stroke and vascular event recurrence rates in secondary prevention trials over the past 50 years and consequences for current trial design. Circulation. 2011;123:2111 5a. O Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, Rangarajan S, Islam S, Pais P, McQueen MJ, et al; INTERSTROKE Investigators. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376:112 6. Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, Chugh S, Mensah GA, Norrving B, Shiue I, Ng M, et al; Global Burden of Diseases, Injuries and Risk Factors Study 2013 and Stroke Experts Writing Group. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a system- atic analysis for the Global Burden of Disease Study 2013. Lancet Neurol. 7. Hackam DG, Spence JD. Combining multiple approaches for the secondary prevention of vascular events after stroke: a quantitative modeling study. 8. Coutts SB, Wein TH, Lindsay MP, Buck B, Cote R, Ellis P, Foley N, Hill MD, Jaspers S, Jin AY, et al; Heart and Stroke Foundation Canada Canadian Stroke Best Practices Advisory Committee. Canadian Stroke Best Prac- tice Recommendations: secondary prevention of stroke guidelines, update 9. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, et al; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association [published cor- rection appears in Stroke. 2015;46:e54]. Stroke. 2014;45:2160 2236. doi: 10. Razmara A, Ovbiagele B, Markovic D, Towfighi A. 