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; Bath, Philip M

Abstract

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). 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. 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. 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. [Abstract copyright: © 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.]

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2022
• Online Publication Date: Jun 8, 2023
• Deposit Date: Jun 29, 2023
• Journal: Stroke and vascular neurology
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Pages: svn-2022-001634
• DOI: https://doi.org/10.1136/svn-2022-001634
• Keywords: Stroke, Clinical Trial, Cerebral Infarction, Blood Pressure