Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis

Appleton, Jason P.; Woodhouse, Lisa J.; Sprigg, Nikola; Wardlaw, Joanna M.; Bath, Philip M.

Abstract

Background: Thrombolysis, with or without thrombectomy, for acute ischaemic stroke is associated with an increased risk of intracranial bleeding. We assessed whether treatment with glyceryl trinitrate (GTN), a nitric oxide donor, may influence the associated bleeding risk. Methods: We searched for completed randomized controlled trials of GTN vs. no GTN in acute ischaemic stroke with data on reperfusion treatments (thrombolysis and/or thrombectomy). The primary efficacy outcome was functional status as assessed by the modified Rankin Scale (mRS) at day 90; the primary safety outcome was intracranial bleeding. Secondary safety outcomes included symptomatic intracranial hemorrhage and haemorrhagic transformation of infarction. Individual patient data were pooled and meta-analysis performed using ordinal or binary logistic regression with adjustment for trial and prognostic variables both overall and in those randomized within 6 h of symptom onset. Results: Three trials met the eligibility criteria. Of 715 patients with ischaemic stroke who underwent thrombolysis (709, >99%) or thrombectomy (24, 3.4%), 357 (49.9%) received GTN and 358 (50.1%) received no GTN. Overall, there was no difference in the distribution of the mRS at day 90 between GTN vs. no GTN (OR 0.94, 95% CI 0.72–1.23; p = 0.65); similarly, there was no difference in intracranial hemorrhage rates between treatment groups (OR 0.90, 95% CI 0.43–1.89; p = 0.77). In those randomized to GTN vs. no GTN within 6 h of symptom onset, there were numerically fewer bleeding events, but these analyses did not reach statistical significance. Conclusions: In ischaemic stroke patients treated predominantly with thrombolysis, transdermal GTN was safe, but did not influence functional outcome at 90 days.

Citation

Appleton, J. P., Woodhouse, L. J., Sprigg, N., Wardlaw, J. M., & Bath, P. M. (2020). Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis. Frontiers in Neurology, 11, Article 584038. https://doi.org/10.3389/fneur.2020.584038

• Journal Article Type: Article
• Acceptance Date: Sep 24, 2020
• Online Publication Date: Oct 20, 2020
• Publication Date: Oct 20, 2020
• Deposit Date: Oct 9, 2020
• Publicly Available Date: Oct 20, 2020
• Journal: Frontiers in Neurology
• Electronic ISSN: 1664-2295
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Article Number: 584038
• DOI: https://doi.org/10.3389/fneur.2020.584038
• Keywords: Bleeding, Glyceryl trinitrate, Ischaemic stroke, Reperfusion, Thrombolysis, Thrombectomy, Meta-analysis
• Public URL: https://nottingham-repository.worktribe.com/output/4949168
• Publisher URL: https://www.frontiersin.org/articles/10.3389/fneur.2020.584038/full
• Additional Information: First published by Frontiers Media.