title: Use of Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke Who Take Non-Vitamin K Antagonist Oral Anticoagulants Before Stroke.
abstract: BACKGROUND
  Intravenous rt-PA (recombinant tissue-type plasminogen activator) is effective in improving outcomes in ischemic stroke; however, there are few data on the use of rt-PA in patients who are receiving a non-vitamin K antagonist oral anticoagulant (NOAC).
  
  
  METHODS
  Using data from the American Heart Association Get With The Guidelines-Stroke Registry, we examined the outcomes of use of thrombolytic therapy in patients with ischemic stroke who received anticoagulation with NOACs versus those on warfarin (international normalized ratio <1.7) or not on anticoagulation from 1289 registry hospitals between October 2012 and March 2015.
  
  
  RESULTS
  Of 42 887 patients with ischemic stroke treated with intravenous rt-PA within 4.5 hours, 251 were taking NOACs (dabigatran 87, rivaroxaban 129, and apixaban 35) before their stroke, 1500 were taking warfarin, and 41 136 were on neither. Patients on NOACs or warfarin were older, had more comorbid conditions, and experienced more severe strokes than did those who were not on anticoagulation (median National Institutes of Health Stroke Scale 12, 13, and 9, respectively). Unadjusted rates of symptomatic intracranial hemorrhage in the NOAC, warfarin, and none groups were 4.8%, 4.9%, and 3.9%, respectively (P=0.11). In comparison with those not on anticoagulation, the adjusted odds ratio for symptomatic intracranial hemorrhage for those on NOACs was 0.92 (95% confidence interval, 0.51-1.65) and for those on warfarin the adjusted odds ratio was 0.85 (95% confidence interval, 0.66-1.10). There were also no significant differences in the risk for life-threatening/serious systemic hemorrhage, any rt-PA complication, in-hospital mortality, and modified Rankin Scale at discharge across 3 groups. Similar results were also found after propensity score matching.
  
  
  CONCLUSIONS
  Although experience of using rt-PA in patients with ischemic stroke on a NOAC is limited, these preliminary observations suggest that rt-PA appears to be reasonably well tolerated without prohibitive risks for adverse events among selected NOAC-treated patients. Future studies should evaluate the safety and efficacy of intravenous rt-PA in patients with ischemic stroke who are taking NOACs.
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.). ying.xian@duke.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xian
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Federspiel
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Lee H
authors.initials: LH
authors.lastname: Schwamm
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: From Duke Clinical Research Institute, Durham, NC (Y.X., A.F.H., E.D.P.); Department of Neurology, Duke University Medical Center, Durham, NC (Y.X., D.T.L.); Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD (J.J.F.); Division of Neurology Massachusetts General Hospital, Boston (L.H.S.); Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.); Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); and Division of Cardiology, University of California, Los Angeles (G.C.F.).
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D000069604:Dabigatran / Q000627:therapeutic use; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000209:etiology; D017052:Hospital Mortality; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D000069552:Rivaroxaban / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; D011994:Recombinant Proteins; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D010959:Tissue Plasminogen Activator; D000069604:Dabigatran
keywords: anticoagulant agents; intracranial hemorrhages; stroke, acute; thrombolysis, therapeutic