Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke

WHO THE FUCK IS GOING TO RUN WITH THIS AND CREATE A HUMAN CLINICAL TRIAL?
I bet nothing will occur because we have NO stroke leadership or stroke strategy. We are completely fucked because we have fucking failures for stroke associations. I weep for your children and grandchildren. Will no one think of the children?
http://stroke.ahajournals.org/content/46/11/3194.abstract?etoc

Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial

1. Lisa Woodhouse, MSc;
2. Polly Scutt, MSc;
3. Kailash Krishnan, MRCP(UK);
4. Eivind Berge, MD, PhD;
5. John Gommans, MD;
6. George Ntaios, MD, PhD;
7. Joanna Wardlaw, FMedSci, FRSE;
8. Nikola Sprigg, MD, MRCP(UK);
9. Philip M. Bath, FRCP, DSc;
10. on behalf of the ENOS Investigators

+ Author Affiliations

1. 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.).

1. Correspondence to Philip M. Bath, FRCP, DSc, Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, City Hospital campus, Hucknall Rd, Nottingham NG5 1PB, United Kingdom. E-mail philip.bath@nottingham.ac.uk

Abstract

Background and Purpose—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.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00989716.