title: Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke: Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial.
abstract: OBJECTIVE
  Nitric oxide donors are candidate treatments for acute stroke, potentially through hemodynamic, reperfusion, and neuroprotectant effects, especially if given early. Although the large Efficacy of Nitric Oxide in Stroke (ENOS) trial of transdermal glyceryl trinitrate (GTN) was neutral, a prespecified subgroup suggested that GTN improved functional outcome if administered early after stroke onset.
  
  
  METHODS
  Prospective analysis of subgroup of patients randomized into the ENOS trial within 6 hours of stroke onset. Safety and efficacy of GTN versus no GTN were assessed using data on early and late outcomes.
  
  
  RESULTS
  Two hundred seventy-three patients were randomized within 6 hours of ictus: mean (SD) age, 69.9 (12.7) years; men, 154 (56.4%); ischemic stroke, 208 (76.2%); Scandinavian Stroke Scale, 32.1 (11.9); and total anterior circulation syndrome, 86 (31.5%). When compared with no GTN, the first dose of GTN lowered blood pressure by 9.4/3.3 mm Hg (P<0.01, P=0.064) and shifted the modified Rankin Scale to a better outcome by day 90, adjusted common odds ratio, 0.51 (95% confidence interval, 0.32-0.80). Significant beneficial effects were also seen with GTN for disability (Barthel Index), quality of life (EuroQol-Visual Analogue Scale), cognition (telephone Mini-Mental State Examination), and mood (Zung Depression Scale). GTN was safe to administer with less serious adverse events by day 90 (GTN 18.8% versus no GTN 34.1%) and death (hazard ratio, 0.44; 95% confidence interval, 0.20-0.99; P=0.047).
  
  
  CONCLUSIONS
  In a subgroup analysis of the large ENOS trial, transdermal GTN was safe to administer and associated with improved functional outcome and fewer deaths when administered within 6 hours of stroke onset.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00989716.
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: Lisa
authors.initials: L
authors.lastname: Woodhouse
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: Polly
authors.initials: P
authors.lastname: Scutt
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: Kailash
authors.initials: K
authors.lastname: Krishnan
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: Eivind
authors.initials: E
authors.lastname: Berge
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: John
authors.initials: J
authors.lastname: Gommans
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: George
authors.initials: G
authors.lastname: Ntaios
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: Joanna
authors.initials: J
authors.lastname: Wardlaw
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.).
authors.forename: Nikola
authors.initials: N
authors.lastname: Sprigg
authors.affiliation: From the Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom (L.W., P.S., K.K., N.S., P.M.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); Stroke Unit, Department of Medicine, Hawke's Bay District Health Board, Hastings, New Zealand (J.G.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); and Division of Neuroimaging Sciences, Clinical Sciences Department, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (J.W.). philip.bath@nottingham.ac.uk.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Bath
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000627:therapeutic use; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000627:therapeutic use; D016037:Single-Blind Method; D020521:Stroke / Q000188:drug therapy*; D061665:Time-to-Treatment; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D005996:Nitroglycerin
keywords: blood pressure; cerebral hemorrhage; nitric oxide; nitroglycerin; stroke