Shorter Door-to-Needle Times are Associated with Better Outcomes after Intravenous Thrombolytic Therapy and Endovascular Thrombectomy for Acute Ischemic Stroke

Background: It remains unclear whether faster door-to-needle times amongst those receiving intravenous thrombolytic therapy (IVT) alone or preceding endovascular thrombectomy (EVT) translate to more home-time, a patient prioritized functional outcome.Methods: This retrospective cohort study included U.S. older patients aged ≥65 years who received IVT within 4·5 hours or EVT within 7 hours for acute ischemic stroke in 2015-2018. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle times and outcomes among IVT only and IVT+EVT group.Findings: The primary analysis included 38913 patients treated with IVT only and 3946 with IVT+EVT. Among IVT only cohort, each 15-minute additional DTN times, up to 90 minutes, was associated with higher odds of zero home-time (death or long-term facility stay) in one year (adjusted OR, 1.04; 95% CI, 1·01-1·07), less home-time among those discharged home (adjusted OR per 1% of 365 days, 0·96; 95% CI, 0·94-0·98), and higher mortality (adjusted HR, 1·03, 95% CI, 1·01-1·04). These associations were stronger in IVT+EVT cohort with aOR 1·12 for zero home-time, 0·93 per 1% home-time, and aHR 1·07 for mortality. Longer DTN (>45 vs ≤45 minutes) were associated with higher adjusted odds of zero home-time in a year in both IVT only and IVT+EVT cohort (1.16 and 1·26), less home-time among those discharged home (0.90 and 0.80 per 1% home-time), and higher mortality (adjusted HR 1.11 and 1·20).Interpretation: Among older stroke patients treated with IVT alone or IVT+EVT, shorter door-to-needle times were associated with better functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients.Funding Information: The Get With The Guidelines®–Stroke (GWTG-Stroke) is provided by the American Heart Association/American Stroke Association. GWTG-Stroke is sponsored, in part, by Novartis, Novo Nordisk, AstraZeneca, Bayer, Tylenol and Alexion, AstraZeneca Rare Disease.Declaration of Interests: SM, NS, BA, and EES reports no relevant disclosure. BMG reports funding from the National Institutes of Health (K23HL161426). MSH reports serving on the scientific advisory board and Clinical events committee of Cerenovus, the principal investigator of Medtronic Core lab, data safety monitoring board for Stryker Neurovascular, and Clinical events committee of Rapid Medical. KU reports being on data safety monitoring board for clinical trials sponsored by Genentech, Inc. and Evaheart, Inc. Consultant for Abbott Laboratories, Inc. JLS reports receiving research support from the National Institute of Health and the American Heart Association; receiving contracted hourly payments from Medtronic, Stryker, Cerenovus, and Boehringer Ingelheim (prevention only) and stock options from Rapid Medical for service on clinical trial steering committees advising on rigorous trial design and conduct; an employee of the University of California which holds a patent on an endovascular devices for stroke. YX reports receiving research funding from the American Heart Association and Genentech and honoraria from Boeheim Ingelheim. DLB discloses the following relationships - Advisory Board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/BristolMyers Squibb clopidogrel litigation), 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), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, 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), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent.) Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. LHS reports serving on the American Heart Association/ GWTG stroke systems of care advisory group and American Stroke Association Advisory Committee; stroke systems consultant to the Massachusetts Department of Public Health; scientific consultant regarding trial design and conduct to Genentech (late window thrombolysis, member of steering committee TIMELESS NCT03785678); member of a Data Safety Monitoring Board (DSMB) for Penumbra (MIND NCT03342664); Diffusion Pharma (PHAST-TSC NCT03763929); National PI or member of National Steering Committee for Medtronic (Stroke AF NCT02700945); PI, StrokeNet Network NINDS (New England Regional Coordinating Center U24NS107243); Co-I, The Impact of Telestroke on Patterns of Care and Long-Term Outcomes, NINDS (R01NS111952). GCF reports receiving research support from the Patient Centered Outcome Research Institute and the National Institutes of Health, and employee of University of California which holds a patent on an endovascular device for stroke.Ethics Approval Statement: Each participating hospital received either human research approval to enroll cases without individual patient consent under the common rule, or a waiver of authorization and exemption from subsequent review by their institutional review board. The Duke Clinical Research Institute serves as the data analysis center and has an agreement to analyze the aggregate deidentified data for research purposes. The Institutional Review Board at Duke University Health approved this study.