Disability After Minor Stroke and Transient Ischemic Attack in the POINT Trial

• Type of Material: Article
• Authors: Brett Cucchiara, University of Pennsylvania; Jordan Elm, Medical University of South Carolina; Donald J Easton, University of California San Francisco; Shelagh B Coutts, University of Calgary; Joshua Z Willey, Columbia University; Michelle H Biros, University of Minnesota, Minneapolis; Michael Ross, Emory University; Claiborne S Johnston, University of Texas Austin
• Language: English
• Date: 2020-03-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, Wolters Kluwer Health
• Final Published Version (URL): http://dx.doi.org/10.1161/STROKEAHA.119.027465
• Title of Journal or Parent Work: STROKE
• Volume: 51
• Issue: 3
• Start Page: 792
• End Page: 799
• Grant/Funding Information: This trial was supported by grants from the National Institute for Neurological Disorders and Stroke, National Institutes of Health (NIH/NINDS U01 NS062835, U01 NS056975, U01 NS059041). The sponsor had no role in the design, conduct, analysis, or presentation of the study. Sanofi provided drug and placebo for 75% of patients in the trial.
• Keywords: humans; Clinical Neurology; ischemic attack, transient; diabetes mellitus; Cardiovascular System & Cardiology; ASPIRIN; Neurosciences & Neurology; Science & Technology; RISK; Peripheral Vascular Disease; Life Sciences & Biomedicine; SEVERITY; stroke; aspirin

Abstract

Background and Purpose—While combination aspirin and clopidogrel reduces recurrent stroke compared with aspirin alone in patients with transient ischemic attack (TIA) or minor stroke, the effect on disability is uncertain. Methods—The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) randomized patients with TIA or minor stroke (National Institutes of Health Stroke Scale score ≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, myocardial infarction, or vascular death. We performed a post hoc exploratory analysis to examine the effect of treatment on overall disability (defined as modified Rankin Scale score >1) at 90 days, as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results—At 90 days, 188 of 1964 (9.6%) of patients enrolled with TIA and 471 of 2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% versus 14.3%; odds ratio, 0.97 [95% CI, 0.82–1.14]; P=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% versus 4.0%; odds ratio, 0.73 [95% CI, 0.53–1.01]; P=0.06) and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% versus 7.4%; odds ratio, 0.78 [95% CI, 0.62–0.99]; P=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% versus 6.0%; odds ratio, 0.74 [95% CI, 0.57–0.96]; P=0.02). In multivariate analysis, age, subsequent ischemic stroke, serious adverse events, and major bleeding were significantly associated with disability in TIA; for those with stroke, female sex, hypertension, or diabetes mellitus, National Institutes of Health Stroke Scale score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events were associated with disability. Conclusions—In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, DAPT might reduce stroke-related disability.