Transdermal delivery of glyceryl trinitrate: clinical applications in acute stroke

ABSTRACT

Introduction

Glyceryl trinitrate (GTN), a nitric oxide donor, is a candidate treatment for the management of acute stroke with hemodynamic and potential reperfusion and neuroprotective effects.

Areas covered

Here we discuss the evidence to date from clinical trials and present and future possibilities for the clinical application of transdermal GTN in acute stroke. When administered as a transdermal patch during the acute and subacute phases after stroke, GTN was safe, lowered blood pressure, maintained cerebral blood flow, and did not induce cerebral steal or alter functional outcome. However, when given within the hyperacute phase (<6 h of stroke onset), GTN reduced death and dependency, death, disability, cognitive impairment, and mood disturbance, and improved quality of life. However, in a large prehospital trial with treatment within 4 h, GTN did not influence clinical outcomes.

Expert opinion

Transdermal GTN is an easy to administer BP-lowering therapy, which is safe when given after 2 h of stroke onset, may improve outcome when initiated within 2–6 h, but should be avoided (outside of a clinical trial) in the ultra-acute period within 2 h of stroke onset. Further research needs to investigate the mechanisms of benefit or harm in ultra/hyperacute stroke patients.

KEYWORDS:

• Acute stroke
• blood pressure
• glyceryl trinitrate
• intracerebral hemorrhage
• ischemic stroke
• nitric oxide

Article highlights

• Transdermal glyceryl trinitrate (GTN) is safe when administered after 2 h of stroke onset.

• Transdermal GTN may improve outcome if administered 2–6 h after stroke onset but may cause harm if used earlier.

• Further research is needed to investigate whether lowering of elevated BP in ultra-acute stroke patients is safe, and if so, efficacious.

This box summarizes key points contained in the article.

Declaration of interest

JP Appleton was funded by the British Heart Foundation (BHF, CS/14/4/30972) and National Institute of Health Research (NIHR) Health Technology Assessment Programme (10/104/24). PM Bath was chief investigator of the trials involving GTN (GTN-1/2/3, ENOS, and RIGHT-1/2), is Stroke Association Professor of Stroke Medicine, and is a NIHR Senior Investigator. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.