Pre-hospital treatment with transdermal glyceryl trinitrate (GTN) in patients with intracranial haemorrhage (ICH) appears to lead to worse outcomes than a sham treatment.
The findings, published in Stroke, were unexpected given previous studies have suggested some benefit from GTN.
In the sub-group analysis of the RIGHT-2 trial, 145 patients with a final hospital diagnosis of ICH were randomised to either GTN or sham treatment – the first doses administered by the paramedic in the ambulance and then subsequent doses administered daily in hospital for three days.
The primary outcome, functional outcome assessed with the 7-level modified Rankin Scale (mRS) at 90 days, was not significantly different between patient groups.
However in four planned sensitivity analyses of the primary outcome, the GTN group had statistically significant worse outcomes than the sham group.
GTN treatment was associated with a significant increase in deaths in hospital and a worse discharge outcome with more patients moved to an institution.
The study also found GTN treated patients had a larger haematoma on admission to hospital and on repeat imaging at day 2.
“In summary, we have shown that the ultra-acute use of GTN may be harmful in patients with ICH and especially within 2 hours. This could result from inhibition of the earliest vasoconstrictory and platelet plugging phases of hemostasis, mechanisms that might apply to other vasodilators,” the study said.
“In this respect, RIGHT-2 is the first large trial to test the effect of inhibiting vasoconstriction in this time-critical period after ICH.”
The overall RIGHT-2 trial of more than 1,100 patients with presumed stroke, published in The Lancet earlier this year, found prehospital treatment with transdermal GTN does not seem to improve functional outcome.
Commenting on the study, Professor Stephen Davis told the limbic GTN has no benefit in acute stroke pre-hospital and might well be harmful in patients with ICH.
Professor Davis, director of the Melbourne Brain Centre at Royal Melbourne Hospital and the University of Melbourne, said the findings had implications for both pre-hospital and in-hospital care.
“I think this study is quite important because we treat patients with ICH with blood pressure lowering drugs in hospital after the diagnosis of ICH. This study would indicate to me that GTN should not be used after the diagnosis of ICH or indeed for stroke before arrival in hospital.”
“It’s an interesting finding. It’s not definitive but I certainly think that based on this, the use of GTN pre-hospital is not warranted and indeed might be harmful in those with ICH.”
“And secondly I would think that has implications for in-hospital treatment because the standard approach in stroke is to do a CT scan and then if they’ve got an ICH, which is 10-15% of patients, the standard of care is to reduce blood pressure and there is no proof of which drug is best. GTN should be avoided given the result of this study.”
“Blood pressure management is important and there is no specific recommended protocol – the original studies used a variety of approaches but GTN should not be used. It has no role in stroke.”