TY - JOUR
T1 - Intravenous Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients with History of Stroke Plus Diabetes Mellitus
AU - Ehrlich, Matthew E.
AU - Liang, Li
AU - Xu, Haolin
AU - Kosinski, Andrzej S.
AU - Hernandez, Adrian F.
AU - Schwamm, Lee H.
AU - Smith, Eric E.
AU - Fonarow, Gregg C.
AU - Bhatt, Deepak L.
AU - Peterson, Eric D.
AU - Xian, Ying
N1 - Funding Information:
This study was supported, in part, by grants from the American Heart Association (AHA; 13CRP14410024 and 14SDG20460081) awarded to Dr Xian. The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the AHA/American Stroke Association. GWTG-Stroke is sponsored, in part, by Medtronic and has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janseen Pharmaceutical Companies of Johnson &Johnson, and the AHA Pharmaceutical Roundtable. The funding organization 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.
Funding Information:
Dr Ehrlich discloses modest research funding from Medtronic Foundation, Chiesi, and Daiichi Sankyo Corp. Dr Kosinski discloses funding from the American Heart Association (AHA), modest. Dr Hernandez discloses research funding from the AHA, AstraZeneca, GlaxoSmithKline, Merck, Luitpold, National Heart, Lung, and Blood Institute, Novartis, Patient Centered Outcomes Research Institute and Verily and consulting for AstraZeneca, Bayer, Boston Scientific, Boehringer Ingelheim, Merck, Novartis, and Pfizer. Dr Schwamm reports being the principal investigator of an investigator-initiated study of extended-window intravenous thrombolysis funded by the National Institutes of Neurological Disorders and Stroke (https:// www.clinicaltrials.gov; NCT01282242) for which Genentech provided alteplase free of charge to the Massachusetts General Hospital, as well as supplemental per-patient payments to participating sites; serving as chair of the AHA/American Stroke Association Get With The Guidelines–Stroke (GWTG-Stroke) clinical work group and hospital accreditation Science Committee and Quality Oversight Committees, cochair of Mission-Lifeline:Stroke; serving as a stroke systems consultant to the Massachusetts Department of Public Health; and serving as a scientific consultant to LifeImage regarding user interface design and usability and regarding trial design and conduct to Lundbeck (international steering committee: DIAS3, 4 trial [Safety and Efficacy of Desmoteplase Given 3–9 H After Ischaemic Stroke in Patients With Occlusion or High-Grade Stenosis in Major Cerebral Arteries]), Penumbra (data and safety monitoring committee: Separator 3D and MIND [A Prospective, Multicenter Study of Artemis a Minimally Invasive Neuro Evacuation Device, in the Removal of Intracerebral Hemorrhage] trials), NovoNordisk (data and safety monitoring committee: DeVOTE trial [Efficacy and Safety of Degludec Versus Glargine in Type 2 Diabetes]), Genentech (steering committee: TIMELESS trial [Tenecteplase in Stroke Patients Between 4 And 24 Hours]), and Medtronic (Victory AF and Stroke AF trials). Dr Fonarow discloses the following relationships: member of GWTG Steering Committee; grant funding from Patient Centered Outcome Research Institute; employee of the University of California, which has a patent on an endovascular therapy device; and consultant at Janssen. Dr Smith has received consulting fees (modest) from Portola Pharmaceuticals and Alnylam Pharmaceuticals. Dr Bhatt discloses the following relationships: belongs to the advisory board at Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; belongs to the board of directors at Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; chair at AHA Quality Oversight Committee; belongs to the data monitoring committees at Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial [Portico Re-Sheathable Transcatheter Aortic Valve System US IDE Trial (PORTICO IDE)], funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial [CENTERA THV System in Intermediate Risk Patients Who Have Symptomatic, Severe, Calcific, Aortic Stenosis Requiring Aortic Valve Replacement], funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial [Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation], funded by Daiichi Sankyo), and Population Health Research Institute; receives honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, American College of Cardiology accreditation committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial [Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting] steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (for the COMPASS [Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease] operations committee, publications committee, steering committee, and US national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/ Treasurer), and WebMD (Continuing Medical Education steering committees); Deputy Editor for Clinical Cardiology; chair for NCDR-ACTION (The National Cardiovascular Data Registry, Myocardial Infarction Get With The Guidelines Registry) Registry Steering Committee and VA CART (Veterans Affairs, Clinical Assessment Reporting And Tracking) Research and Publications Committee; reports research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, and The Medicines Company; royalties from Elsevier (Editor, “Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease”); site coinvestigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; trustee at the American College of Cardiology; and unfunded research at FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. Dr Peterson discloses research funding from Genentech. Dr Xian reports research grant to the Duke Clinical Research Institute from Genentech.
Funding Information:
This study was supported, in part, by grants from the American Heart Association (AHA; 13CRP14410024 and 14SDG20460081) awarded to Dr Xian. The Get With The Guidelines–Stroke (GWTG-Stroke) program is provided by the AHA/American Stroke Association. GWTG-Stroke is sponsored, in part, by Medtronic and has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janseen Pharmaceutical Companies of Johnson & Johnson, and the AHA Pharmaceutical Roundtable. The funding organization 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.
Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019
Y1 - 2019
N2 - Background and Purpose-Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods-Using data from the Get With The Guidelines-Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3-to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results-Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5-15] versus 7 [4-13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P=0.31) and 6.2% versus 5.5% (P=0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51-1.21]; P=0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52-1.14]; P=0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0-2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59-0.99]; P=0.04). Conclusions-Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3-to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.
AB - Background and Purpose-Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods-Using data from the Get With The Guidelines-Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3-to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results-Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5-15] versus 7 [4-13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P=0.31) and 6.2% versus 5.5% (P=0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51-1.21]; P=0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52-1.14]; P=0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0-2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59-0.99]; P=0.04). Conclusions-Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3-to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.
KW - diabetes mellitus
KW - stroke
KW - thrombolysis
KW - tissue-type plasminogen activator
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U2 - 10.1161/STROKEAHA.118.024172
DO - 10.1161/STROKEAHA.118.024172
M3 - Article
C2 - 31035901
AN - SCOPUS:85067266309
SN - 0039-2499
VL - 50
SP - 1497
EP - 1503
JO - Stroke
JF - Stroke
IS - 6
ER -