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Association Between Thrombolytic Door-to-Needle Time and 1-Year Mortality and Readmission in Patients With Acute Ischemic Stroke

Educational Objective
To understand the benefits of rapid administration of intravenous tissue plasminogen activator after acute ischemic stroke.
1 Credit CME
Key Points

Question  Is there an association between shorter door-to-needle time with thrombolytic therapy and long-term mortality and hospital readmission in patients with acute ischemic stroke?

Findings  In this US retrospective cohort study that included 61 426 patients with acute ischemic stroke treated with intravenous tissue plasminogen activator, longer door-to-needle times (within 90 minutes after hospital arrival) were significantly associated with higher all-cause mortality at 1 year (hazard ratio per 15-minute increase in time, 1.04) and higher likelihood of all-cause readmission at 1 year (hazard ratio per 15-minute increase in time, 1.02).

Meaning  These findings support efforts to shorten time to thrombolytic therapy.

Abstract

Importance  Earlier administration of intravenous tissue plasminogen activator (tPA) in acute ischemic stroke is associated with reduced mortality by the time of hospital discharge and better functional outcomes at 3 months. However, it remains unclear whether shorter door-to-needle times translate into better long-term outcomes.

Objective  To examine whether shorter door-to-needle times with intravenous tPA for acute ischemic stroke are associated with improved long-term outcomes.

Design, Setting, and Participants  This retrospective cohort study included Medicare beneficiaries aged 65 years or older who were treated for acute ischemic stroke with intravenous tPA within 4.5 hours from the time they were last known to be well at Get With The Guidelines–Stroke participating hospitals between January 1, 2006, and December 31, 2016, with 1-year follow-up through December 31, 2017.

Exposures  Door-to-needle times for intravenous tPA.

Main Outcomes and Measures  The primary outcomes were 1-year all-cause mortality, all-cause readmission, and the composite of all-cause mortality or readmission.

Results  Among the 61 426 patients treated with tPA within 4.5 hours, the median age was 80 years and 43.5% were male. The median door-to-needle time was 65 minutes (interquartile range, 49-88 minutes). The 48 666 patients (79.2%) who were treated with tPA and had door-to-needle times of longer than 45 minutes, compared with those treated within 45 minutes, had significantly higher all-cause mortality (35.0% vs 30.8%, respectively; adjusted HR, 1.13 [95% CI, 1.09-1.18]), higher all-cause readmission (40.8% vs 38.4%; adjusted HR, 1.08 [95% CI, 1.05-1.12]), and higher all-cause mortality or readmission (56.0% vs 52.1%; adjusted HR, 1.09 [95% CI, 1.06-1.12]). The 34 367 patients (55.9%) who were treated with tPA and had door-to-needle times of longer than 60 minutes, compared with those treated within 60 minutes, had significantly higher all-cause mortality (35.8% vs 32.1%, respectively; adjusted hazard ratio [HR], 1.11 [95% CI, 1.07-1.14]), higher all-cause readmission (41.3% vs 39.1%; adjusted HR, 1.07 [95% CI, 1.04-1.10]), and higher all-cause mortality or readmission (56.8% vs 53.1%; adjusted HR, 1.08 [95% CI, 1.05-1.10]). Every 15-minute increase in door-to-needle times was significantly associated with higher all-cause mortality (adjusted HR, 1.04 [95% CI, 1.02-1.05]) within 90 minutes after hospital arrival, but not after 90 minutes (adjusted HR, 1.01 [95% CI, 0.99-1.03]), higher all-cause readmission (adjusted HR, 1.02; 95% CI, 1.01-1.03), and higher all-cause mortality or readmission (adjusted HR, 1.02 [95% CI, 1.01-1.03]).

Conclusions and Relevance  Among patients aged 65 years or older with acute ischemic stroke who were treated with tissue plasminogen activator, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year. These findings support efforts to shorten time to thrombolytic therapy.

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Article Information

Corresponding Author: Gregg C. Fonarow, MD, Ahmanson-UCLA Cardiomyopathy Center, UCLA Medical Center, 10833 LeConte Ave, Los Angeles, CA 90095 (gfonarow@mednet.ucla.edu).

Accepted for Publication: April 9, 2020.

Author Contributions: Dr Fonarow had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Man, Xian, Saver, Fonarow.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Man, Xian.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Xian, Holmes, Matsouaka.

Obtained funding: Fonarow.

Administrative, technical, or material support: Fonarow.

Supervision: Matsouaka, Saver, Fonarow.

Conflict of Interest Disclosures: Dr Xian reported receiving grants from Genentech; and receiving personal fees from Boehringer Ingelheim. Ms Holmes reported receiving personal fees from the American Heart Association. Dr Saver reported receiving research support from the National Institutes of Health and the American Heart Association; receiving contracted hourly payments from Medtronic, Stryker, Cerenovus, and Boehringer Ingelheim; having stock options in Rapid Medical; and being an employee of the University of California, which holds a patent on an endovascular device for stroke. Dr Bhatt disclosed the following relationships—advisory board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, PLx Pharma, and Regado Biosciences; board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; chair: American Heart Association Quality Oversight Committee; data monitoring committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), and Population Health Research Institute; honoraria: American College of Cardiology (ACC) (senior associate editor of Clinical Trials and News and ACC.org; vice chair of ACC accreditation committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), Medtelligence/ReachMD (continuing medical education [CME] steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (CME steering committees); other: Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (chair), VA CART Research and Publications Committee (chair); research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, the Medicines Company, and TobeSoft; royalties: Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); site co-investigator: Biotronik, Boston Scientific, CSI, St Jude Medical (now Abbott), and Svelte; trustee: American College of Cardiology; and unfunded research: FlowCo, Merck, Novo Nordisk, and Takeda. Dr Schwamm reported serving as the chair of the American Heart Association/American Stroke Association Get With The Guidelines–Stroke work group and the American Stroke Association advisory committee; serving as a stroke systems consultant to the Massachusetts Department of Public Health; serving as a scientific consultant regarding trial design and conduct to Genentech (late window thrombolysis and member of steering committee for TIMELESS); serving as a member of data and safety monitoring boards for Penumbra (MIND) and Diffusion Pharma (PHAST-TSC); serving as a principal investigator or a member of the national steering committee for Medtronic (Stroke AF) and the National Institute of Neurological Disorders and Stroke (MR WITNESS, StrokeNet Network, and Impact of Telestroke on Patterns of Care and Long-Term Outcomes); and receiving personal fees from Boehringer Ingleheim, Diffusion Pharma, Genentech, Medtronic, and Penumbra. Dr Fonarow reported receiving research support from the Patient-Centered Outcomes Research Institute and the National Institutes of Health; and being an employee of the University of California, which holds a patent on an endovascular device for stroke. No other disclosures were reported.

Funding/Support: The Get With The Guidelines–Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. GWTG-Stroke is sponsored, in part, by Novartis, Boehringer Ingelheim Lilly, Novo Nordisk, Sanofi, AstraZeneca, and Bayer.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: Dr Saver is Associate Editor of JAMA and Dr Fonarow is Associate Editor of JAMA Cardiology, but neither was not involved in any of the decisions regarding review of the manuscript or its acceptance.

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