Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute stroke.
BACKGROUND
Nitric oxide has several effects that may be beneficial in ischaemic stroke and useful in the management of high blood pressure in acute stroke. Some forms of nitric oxide synthase inhibition may also be beneficial. However, high concentrations of nitric oxide are likely to be toxic to brain tissue.


OBJECTIVE
The objective of this review was to assess the effects of nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in people with acute stroke.


METHODS
We searched the Cochrane Stroke Group Trials Register (last searched in March 2002), EMBASE (1980-March 2002), MEDLINE (1966-March 2002), and ISI Science Citation Indexes (1981-March 2002). We contacted drug companies and researchers in the field.


METHODS
Randomised and quasi-randomised trials comparing nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in patients within one week of onset of confirmed stroke.


METHODS
Two reviewers independently applied the inclusion criteria. The data are given as weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CI).


RESULTS
Two small completed trials (127 patients) of transdermal glyceryl trinitrate (GTN), a nitric oxide donor, were found. GTN lowered 24 hour ambulatory systolic blood pressure by 7.9 mmHg (95% CI 0.1, 15.8) and increased heart rate (WMD 6.2 beats per minute, 95% CI 2.7, 9.8). Treatment with GTN was not associated with statistically significant effects on end-of-treatment death, or combined death or deterioration, or end-of-trial death, combined death or dependency, or combined death or institutionalisation.


CONCLUSIONS
There is currently insufficient evidence from randomised trials on the effects of nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in patients with acute stroke to recommend their use. A large controlled trial of glyceryl trinitrate patches is underway.
Bath
P M
PM
Division of Stroke Medicine, University of Nottingham, City Hospital Campus, Hucknall Road, Nottingham, Nottinghamshire, UK, NG5 1PB. philip.bath@nottingham.ac.uk
Willmot
M
M
Leonardi-Bee
J
J
Bath
F J
FJ
D001120:Arginine / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000188:drug therapy*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D001120:Arginine; D019001:Nitric Oxide Synthase