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

Appleton, Jason Philip, Woodhouse, Lisa J., Anderson, Craig S., Ankolekar, Sandeep, Cala, Lesley, Dixon, Mark, England, Timothy J., Krishnan, Kailash, Mair, Grant, Muir, Keith W., Potter, John, Price, Christopher I., Randall, Marc, Robinson, Thompson G., Roffe, Christine, Sandset, Else C., Saver, Jeffrey L., Shone, Angela, Siriwardena, Aloysius Niroshan, Wardlaw, Joanna M., Sprigg, Nikola and Bath, Philip M. and On behalf of the RIGHT-2 Investigators (2023) Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial. Stroke and Vascular Neurology, 9 (1). pp. 38-49. ISSN 2059-8688

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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.

Item Type: Article
Additional Information: Data availability statement: Data are available on reasonable request to the corresponding author. Funding: British Heart Foundation (grant number CS/14/4/30972). JPA is supported by an NIHR Health and Care Research Scholarship. PMB is Stroke Association Professor of Stroke Medicine and an NIHR Senior Investigator. TR is an NIHR Senior Investigator. GM is the Stroke Association Edith Murphy Foundation Senior Clinical Lecturer (SA L-SMP 18\1000). JW is supported by the UK Dementia Research Institute which receives its funding from DRI, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK.
Uncontrolled Keywords: blood pressure,cerebral infarction,clinical trial,stroke,clinical neurology,cardiology and cardiovascular medicine ,/dk/atira/pure/subjectarea/asjc/2700/2728
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health
Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
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Depositing User: LivePure Connector
Date Deposited: 17 Jul 2023 10:43
Last Modified: 08 Mar 2024 09:30
DOI: 10.1136/svn-2022-001634


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