Time Course of Evolution of Disability and Cause‐Specific Mortality After Ischemic Stroke: Implications for Trial Design

Abstract

BackgroundOutcome 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 ResultsIn 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‐stroke‐related 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%]).ConclusionsOur 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.

Updated Criteria for Population-Based Stroke and Transient Ischemic Attack Incidence Studies for the 21st Century

“…Suggested additional supplementary data collection also includes registration of recurrent TIA (because recurrent TIA has different management and prognostic significance); capture-recapture estimates to ascertain the completeness of stroke and TIA case ascertainment, 51,52 follow-up of stroke and TIA patients' functional status for at least 3 months (there is evidence that 3-month disability, as measured by the modified Rankin Scale pre-and post-stroke, is a strong independent predictor of long-term disability and mortality); 53,54 and collecting data on risk factors among stroke and TIA patients to allow firmer conclusions to be drawn about the factors impacting the trends in incidence and outcomes as well as to reflect on the effect of trends in health policy on stroke and TIA outcomes. 41,55 Complete, population-based case ascertainment, based on multiple overlapping sources of information (hospitals, outpatient clinics, general practitioners, death certificates) and high level of acute brain neuroimaging coverage, with an expert adjudication of the events is very important for the capture and diagnosis/classification of all new stroke and TIA cases 24 based on both old (clinical) and new stroke and TIA definitions.…”

Incidence and Etiologies of Stroke Mimics After Incident Stroke or Transient Ischemic Attack

“…Mortality after stroke is mainly due to cardiovascular causes and is consistently associated with cardiovascular risk factors across studies. 15,33,39,42,45,188,194,273,274,276,[278][279][280][281][282] One of these cardiovascular causes is recurrent stroke, but despite recurrence being frequent and devastating, few studies have assessed the impact recurrent stroke has on all-cause mortality. In one of the first studies investigating this matter, Sacco et al found no difference in mortality for incident ischemic stroke compared with those with prior stroke in the NOMAS study.…”

circRNAs: Potential Targets for the Prevention and Treatment of Cerebrovascular Diseases

“…Ischemic cerebrovascular disease is usually acute onset; it is characterized by high incidence, high mortality, and high disability rate [27][28][29] due to the lack of effective treatment methods. Atherosclerosis is an important risk factor for ischemic stroke; it is the key to the prevention and treatment of stroke [30][31][32].…”