The effect of nitroglycerin treatment on cerebral ischaemia: A systematic review and meta-analysis of animal studies.

Background: Nitroglycerin has been of considerable interest as a treatment for ischaemic stroke. Recent clinical trials with nitroglycerin transdermal patches during the acute phase of stroke failed to improve functional outcomes. Systematic review and meta-analysis of the effectiveness of nitroglycerin in preclinical models of ischaemic stroke has not previously been reported, despite several clinical trials.
Objective: To conduct a systematic review and meta-analysis of preclinical evidence regarding the effect of nitroglycerin on infarct volume in animal models of ischaemic stroke.
Summary of Review: The protocol was registered in PROSPERO (CRD42023432644). Our search identified 238 publications. Three publications met inclusion criteria (including 10 comparisons of infarct size). Study quality was modest (median 6 out of 9), with no evidence of publication bias. Nitroglycerin did not significantly reduce infarct volume (NMD point estimate 20.2 % reduction, 95 % CI -1.52-52.7 %, p = 0.068). Subgroup analysis suggested greater efficacy of nitroglycerin with direct intracarotid administration to the ischaemic territory at the time of reperfusion.
Conclusions: A small number of studies (three) were included in this review. Overall, nitroglycerin did not reduce infarct volume in experimental stroke models. However, nitroglycerin may be of benefit when administered directly into the ischaemic territory. Given nitroglycerin's short half-life, we propose this route may minimise harmful reduction of cerebral perfusion pressure resulting from hypotension following systemic administration.
Competing Interests: Declaration of competing interest D.J.B. is an inventor; and The University of Newcastle is applicant for the patent: Stroke Treatment (WO 2022/072,348), related to the delivery of nitrates to the brain during stroke.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)