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Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial

Lookup NU author(s): Dr Christopher Price



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Background: The effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2). Methods: RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4 hours of onset. The primary outcome was a shift in scores on the modified Rankin scale (mRS) at day 90. Secondary outcomes included death; a global analysis (Wei-Lachin test) containing Barthel Index, EuroQol-5D, mRS, telephone interview for cognitive status-modified and Zung depression scale; and neuroimaging-determined 'brain frailty' markers. Data were reported as n (%), mean (SD), median [IQR], adjusted common OR (acOR), mean difference or Mann-Whitney difference (MWD) with 95% CI. Results: 597 of 1149 (52%) patients had a final diagnosis of ischaemic stroke; age 75 (12) years, premorbid mRS>2 107 (18%), Glasgow Coma Scale 14 (2) and time from onset to randomisation 67 [45, 108] min. Neuroimaging 'brain frailty' was common: median score 2 [2, 3] (range 0-3). At day 90, GTN did not influence the primary outcome (acOR for increased disability 1.15, 95% CI 0.85 to 1.54), death or global analysis (MWD 0.00, 95% CI -0.10 to 0.09). In subgroup analyses, there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1 hour of symptom onset and in those with more severe stroke. Conclusions: In patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.

Publication metadata

Author(s): Appleton JP, Woodhouse LJ, Anderson CS, Ankolekar S, Cala L, Dixon M, England TJ, Krishnan K, Mair G, Muir KW, Potter J, Price CI, Randall M, Robinson TG, Roffe C, Sandset EC, Saver JL, Shone A, Siriwardena AN, Wardlaw JM, Sprigg N, Bath PM

Publication type: Article

Publication status: Published

Journal: Stroke and Vascular Neurology

Year: 2023

Pages: epub ahead of print

Online publication date: 08/06/2023

Acceptance date: 12/08/2022

Date deposited: 04/08/2023

ISSN (print): 2059-8688

ISSN (electronic): 2059-8696

Publisher: BMJ Publishing Group


DOI: 10.1136/svn-2022-001634

PubMed id: 37290930


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Funder referenceFunder name
Alzheimer’s Research UK
Alzheimer’s Society
British Heart Foundation
Medical Research Council
SA L-SMP 18\1000
Stroke Association