Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis
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 co...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-10-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2020.584038/full |
| _version_ | 1819072171703533568 |
|---|---|
| author | Jason P. Appleton Jason P. Appleton Lisa J. Woodhouse Nikola Sprigg Nikola Sprigg Joanna M. Wardlaw Philip M. Bath Philip M. Bath |
| author_facet | Jason P. Appleton Jason P. Appleton Lisa J. Woodhouse Nikola Sprigg Nikola Sprigg Joanna M. Wardlaw Philip M. Bath Philip M. Bath |
| author_sort | Jason P. Appleton |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T17:33:29Z |
| format | Article |
| id | doaj.art-60f148bbf64842c082c39a93cf8c0937 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-21T17:33:29Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-60f148bbf64842c082c39a93cf8c09372022-12-21T18:55:51ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-10-011110.3389/fneur.2020.584038584038Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-AnalysisJason P. Appleton0Jason P. Appleton1Lisa J. Woodhouse2Nikola Sprigg3Nikola Sprigg4Joanna M. Wardlaw5Philip M. Bath6Philip M. Bath7Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United KingdomStroke, University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, United KingdomStroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United KingdomStroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United KingdomStroke, Nottingham University Hospitals National Health Service Trust, Nottingham, United KingdomCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United KingdomStroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United KingdomStroke, Nottingham University Hospitals National Health Service Trust, Nottingham, United KingdomBackground: 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.https://www.frontiersin.org/articles/10.3389/fneur.2020.584038/fullbleedingglyceryl trinitrateischaemic strokereperfusionthrombolysisthrombectomy |
| spellingShingle | Jason P. Appleton Jason P. Appleton Lisa J. Woodhouse Nikola Sprigg Nikola Sprigg Joanna M. Wardlaw Philip M. Bath Philip M. Bath 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 bleeding glyceryl trinitrate ischaemic stroke reperfusion thrombolysis thrombectomy |
| title | Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis |
| title_full | Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis |
| title_fullStr | Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis |
| title_full_unstemmed | Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis |
| title_short | Intracranial Bleeding After Reperfusion Therapy in Acute Ischaemic Stroke Patients Randomized to Glyceryl Trinitrate vs. Control: An Individual Patient Data Meta-Analysis |
| title_sort | intracranial bleeding after reperfusion therapy in acute ischaemic stroke patients randomized to glyceryl trinitrate vs control an individual patient data meta analysis |
| topic | bleeding glyceryl trinitrate ischaemic stroke reperfusion thrombolysis thrombectomy |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2020.584038/full |
| work_keys_str_mv | AT jasonpappleton intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis AT jasonpappleton intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis AT lisajwoodhouse intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis AT nikolasprigg intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis AT nikolasprigg intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis AT joannamwardlaw intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis AT philipmbath intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis AT philipmbath intracranialbleedingafterreperfusiontherapyinacuteischaemicstrokepatientsrandomizedtoglyceryltrinitratevscontrolanindividualpatientdatametaanalysis |