Spotlight on Research

Except for the RIGHT-2 study, pooled analyses of previous studies suggest that very early treatment with glyceryl trinitrate (GTN) of patients with acute ischaemic stroke or intracerebral haemorrhage improves functional outcome. This randomised, open-label, blinded endpoint trial sought to assess whether patients with presumed acute stroke would benefit from GTN commenced within 3 hours of symptom onset. Six ambulance services in the Netherlands recruited eligible adult participants (≥18 years) who had a probable diagnosis of acute stroke (as assessed by a paramedic), a FAST score of 2 or 3, systolic blood pressure of ≥140 mmHg, and could start treatment within 3 hours of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, to receive either transdermal GTN or standard care alone. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. The target sample size was 1400 patients.

The trial was prematurely terminated with only 380 patients randomly allocated to a study group. There were 325 included in the analysis, with 170 assigned to the GTN group and 155 to the control group. In total, 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the target population (n=291), the 90-day mRS score was 2 (2–4) in the glyceryl trinitrate group and 3 (1–4) in the control group. There were no differences between the two study groups with respect to death within 90 days or serious adverse events; however, 12 (34%) of 35 patients with intracerebral haemorrhage died within 7 days in the GTN group versus 2 (10%) of 21 in the control group; death within 90 days occurred in 16 (46%) of 35 in the GTN group and 11 (55%) of 20 in the control group. There was no evidence of benefit of transdermal GTN in this study but there was potential for harm to those with intracerebral haemorrhage.