Kailash Krishnan1, Polly Scutt1, Lisa Woodhouse1, Alessandro Adami1, Jennifer L Becker1, Eivind Berge1, Lesley A Cala1, Ana M Casado1, Valeria Caso1, Christopher Chen1, Hanna Christensen1, Ronan Collins1, Anna Czlonkowska1, Robert A Dineen1, John Gommans1, Panos Koumellis1, Kennedy R Lees1, George Ntaios1, Serefnur Ozturk1, Stephen J Phillips1, Stuart J Pocock1, Asita de Silva1, Nikola Sprigg1, Szabolcs Szatmari1, Joanna M Wardlaw1, Philip M Bath2. 1. From the Stroke Trials Unit, Division of Clinical Neuroscience (K.K., P.S., L.W., N.S., P.M.B.) and Radiological Sciences Research Group, Division of Clinical Neuroscience (R.A.D.), University of Nottingham, Nottingham, United Kingdom; Stroke Centre, Ospedale Sacro Cuore, Verona, Italy (A.A.); Department of Medical Imaging, College of Medicine, The University of Arizona, Tucson (J.L.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia (L.A.C.); Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Western General Hospital, Edinburgh, United Kingdom (A.M.C., J.M.W.); Stroke Unit, Santa Maria Hospital, University of Perugia, Perugia, Italy (V.C.); Department of Pharmacology, National University of Singapore, Singapore, Singapore (C.C.); Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark (H.C.); Stroke Service, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland (R.C.); Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C.); Department of Medicine, Hawke's Bay Hospital, Hastings, New Zealand (J.G.); Department of Neuroradiology, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United Kingdom (P.K.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); Department of Neurology, Selcuk University Medical Faculty, Konya, Turkey (S.O.); Division of Neurology, Dalhousie University, Halifax, Canada (S.J. Phillips); Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom (S.J. Pocock); Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka (A.d.S.); and Department of Neurology, Clinical County Emergency Hospital, Targu Mures, Romania (S.S.). 2. From the Stroke Trials Unit, Division of Clinical Neuroscience (K.K., P.S., L.W., N.S., P.M.B.) and Radiological Sciences Research Group, Division of Clinical Neuroscience (R.A.D.), University of Nottingham, Nottingham, United Kingdom; Stroke Centre, Ospedale Sacro Cuore, Verona, Italy (A.A.); Department of Medical Imaging, College of Medicine, The University of Arizona, Tucson (J.L.B.); Department of Internal Medicine, Oslo University Hospital, Oslo, Norway (E.B.); School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Australia (L.A.C.); Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, Western General Hospital, Edinburgh, United Kingdom (A.M.C., J.M.W.); Stroke Unit, Santa Maria Hospital, University of Perugia, Perugia, Italy (V.C.); Department of Pharmacology, National University of Singapore, Singapore, Singapore (C.C.); Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark (H.C.); Stroke Service, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland (R.C.); Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C.); Department of Medicine, Hawke's Bay Hospital, Hastings, New Zealand (J.G.); Department of Neuroradiology, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United Kingdom (P.K.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); Department of Neurology, Selcuk University Medical Faculty, Konya, Turkey (S.O.); Division of Neurology, Dalhousie University, Halifax, Canada (S.J. Phillips); Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom (S.J. Pocock); Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka (A.d.S.); and Department of Neurology, Clinical County Emergency Hospital, Targu Mures, Romania (S.S.). philip.bath@nottingham.a
Abstract
BACKGROUND AND PURPOSE: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. METHODS: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. RESULTS: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. CONCLUSIONS: In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN99414122. Unique identifier: 99414122.
BACKGROUND AND PURPOSE: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. METHODS: In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. RESULTS: Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. CONCLUSIONS: In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN99414122. Unique identifier: 99414122.
Authors: Brandi M Wynne; Hicham Labazi; Zidonia N Carneiro; Rita C Tostes; R Clinton Webb Journal: Eur J Pharmacol Date: 2017-08-20 Impact factor: 4.432
Authors: Pitchaiah Mandava; Santosh B Murthy; Neel Shah; Yves Samson; Marek Kimmel; Thomas A Kent Journal: Neurology Date: 2019-03-20 Impact factor: 11.800
Authors: Gregory Y H Lip; Deirdre A Lane; Radosław Lenarczyk; Giuseppe Boriani; Wolfram Doehner; Laura A Benjamin; Marc Fisher; Deborah Lowe; Ralph L Sacco; Renate Schnabel; Caroline Watkins; George Ntaios; Tatjana Potpara Journal: Eur Heart J Date: 2022-07-07 Impact factor: 35.855