Time course of evolution of disability and cause-specific mortality after ischemic stroke: Implications for trial design

Background-outcome in stroke trials is often based on a 3-month modified rankin scale (mrs). how 3-month mrs relates to longer-term outcomes will depend on late recovery,delayed stroke-related deaths,recurrent strokes,and nonstroke deaths. we evaluated 3-month mrs and death/disability at 1 and 5 years in a population-based cohort study. methods and results-in 3-month survivors of ischemic stroke (oxford vascular study; 2002-2014),we related 3-month mrs to disability (defined as mrs > 2) at 1 and 5 years and/or death rates (age/sex adjusted). accrual of disability and index-strokerelated and nonstroke deaths in each poststroke year was categorized according to 3-month mrs. among 1606 patients with acute ischemic stroke,181 died within 3 months,but 126 index-stroke-related deaths and 320 other deaths occurred during the subsequent 4866 patient-years of follow-up up to 5 years. although 69/126 (54.8%) post-3-month index-stroke-related deaths occurred after 1 year,mrs > 2 at 1 year strongly predicted these deaths (adjusted hazard ratio=21.94,95%ci 7.88-61.09,p < 0.0001). consequently,a 3-month mrs > 2 was a strong independent predictor of death at both 1 year (adjusted hazard ratio=6.67,95%ci 4.16-10.69,p < 0.0001) and 5 years (adjusted hazard ratio=2.93,95%ci 2.38-3.60,p < 0.0001). although mrs improved by ≥1 point from 3 months to 1 year in 317/1266 (25.0%) patients with 3-month mrs ≥1,improvement in mrs after 1 year was limited (improvement by =1 point: 91/858 [10.6%]; improvement to mrs ≤2: 13/353 [3.7%]). conclusions-our results reaffirm use of the 3-month mrs outcome in stroke trials. although later recovery does occur,extending follow-up to 1 year would capture most long-term stroke-related disability. however,administrative mortality follow-up beyond 1 year has the potential to demonstrate translation of early disability gains into additional reductions in long-term mortality without much erosion by non-stroke-related deaths. © 2017 the authors.