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

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.

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2022
• Online Publication Date: Jun 8, 2023
• Publication Date: Jun 8, 2023
• Deposit Date: Jun 21, 2023
• Publicly Available Date: Jun 21, 2023
• Journal: Stroke and Vascular Neurology
• Electronic ISSN: 2059-8696
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• DOI: https://doi.org/10.1136/svn-2022-001634
• Keywords: Stroke, Clinical Trial, Cerebral Infarction, Blood Pressure
• Public URL: https://nottingham-repository.worktribe.com/output/21646408
• Publisher URL: https://svn.bmj.com/content/early/2023/06/08/svn-2022-001634