Netherlands: A study published in The Lancet Neurology has concluded that there is no benefit of transdermal glyceryl trinitrate within 3 hours of symptom onset in patients with presumed acute stroke.
The research also highlighted that the clinical use of glyceryl trinitrate should be avoided in patients with presumed acute stroke.
Previous studies have mentioned that very early treatment with glyceryl trinitrate or nitroglycerin improves functional outcomes in acute ischaemic stroke patients or intracerebral haemorrhage.

The update here is these findings were not confirmed in RIGHT-2, a more recent trial.
Considering this, a team of researchers assessed.
What is the benefit received by presumed acute stroke patients when they are given glyceryl trinitrate, which is started within three h after the onset of symptoms?
The lead researcher was Dr Sophie A van den Berg, MD from the Department of Neurology at Amsterdam.
The key points of the study design are:
• MR ASAP was an ambulance-based, blinded endpoint, Phase 3 trial.
• The age of the eligible participants was≥18 years.
• The participants had a history of acute stroke.
• The face-arm-speech-time test score was 2 or 3.
• The systolic blood pressure was at least 140 mm Hg.
• The treatment was started within three h of the onset of symptoms.
• There were two groups, the glyceryl trinitrate group and the control group.
• The glyceryl trinitrate group received transdermal glyceryl trinitrate 5 mg/day for 24 h combined with standard care.
• The control group received standard care alone.
• The participants were assigned in a ratio of 1:1 by ambulance personnel.
• A secure web-based electronic application was used.
• The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. This was the primary outcome.
• Death within 7 and 90 days, and serious adverse events were included in the safety outcomes.
• Modified intention to treat was used in analyses.
• Odds ratios (ORs) were used to express treatment effects.
• The target population was intracerebral haemorrhage patients, ischaemic stroke patients , or transient ischaemic attack patients.
• The target sample size was 1400 patients.
MR ASAP trial was prematurely terminated concerning safety issues in a patient with intracerebral haemorrhage.
• Three hundred eighty patients were randomly allocated to a study group (Between April 4, 2018, and February 12, 2021).
• Two hundred-one patients constituting 62%, had an ischaemic stroke.
• Thirty-four patients constituting 10%, had transient ischaemic attacks.
• 56 patients constituting 17% intracerebral haemorrhage.
• Thirty-four patients (10%) had a stroke-mimicking condition.
• There was a total of 325 patients in the total population.
At 90 days, the median mRS score was 2 in both groups with an adjusted common OR of 0·97.
• A total of 291 patients were included in the target population. The recorded 90-day mRS score was 2 in both groups.
• There were no differences recorded between the two study groups concerning death within 90 days in the total population with (adjusted OR of 1·07 or serious adverse events with unadjusted OR 1·23.
• In intracerebral haemorrhage patients, 12 of 35 patients in glyceryl trinitrate versus 2 of 21 in the control group died within seven days. The adjusted OR was 5·91.
Within 90 days, death occurred in 16 patients out of 35 in the glyceryl trinitrate group and 11 out of 20 in the control group with an adjusted OR of 0·87.
The researchers interpreted that,
"We found no benefit sign of transdermal glyceryl trinitrate started within three hours of onset of symptoms in the prehospital setting in presumed acute stroke patients."
"The signal of early harm of glyceryl trinitrate in intracerebral haemorrhage patients suggests that glyceryl trinitrate should be avoided in this setting", they mentioned.
As acknowledged, the funding was provided by The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.
Further reading
Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP): an ambulance-based, multicentre, randomised, open-label, blinded endpoint, phase 3 trial. Sophie A van den Berg et al.