title: Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.
abstract: Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.
authors.affiliation: Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham NG5 1PB, UK.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Bath
authors.affiliation: Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham NG5 1PB, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Woodhouse
authors.affiliation: Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham NG5 1PB, UK.
authors.forename: Kailash
authors.initials: K
authors.lastname: Krishnan
authors.affiliation: Neurological & Mental Health Division, University of Sydney, Sydney, NSW 2000, Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Department of Internal Medicine, Oslo University Hospital, 0424 Oslo, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Berge
authors.affiliation: Oxford Academic Health Sciences Network, Oxford University Hospitals, NHS Trust, Oxford OX4 4GA, UK.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ford
authors.affiliation: Department of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Disease, University of Leicester, Leicester LE3 9QP, UK.
authors.forename: Thompson G
authors.initials: TG
authors.lastname: Robinson
authors.affiliation: Geffen School of Medicine at UCLA, UCLA Comprehensive Stroke Center, Los Angeles, CA 90095, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.affiliation: Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham NG5 1PB, UK.
authors.forename: Nikola
authors.initials: N
authors.lastname: Sprigg
authors.affiliation: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.affiliation: University of Nottingham, Nottingham NG5 1PB, UK.
authors.forename: Blood Pressure
authors.initials: BP
authors.lastname: In Acute Stroke Collaboration Basc