Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of
lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke
remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric
oxide donor, might improve outcome when administered very early after stroke onset.
Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled,
blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2
or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive
transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbased ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment,
whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of
functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was
hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all
participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This
trial is registered with ISRCTN, number ISRCTN26986053.
Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited
1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min
(IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had
transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN
group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001),
and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in
mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1):
3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor
outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2:
3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no
difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group
[p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment
groups.
Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients
with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting
