Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries

Introduction: The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary preven...

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Main Authors: Hinwood, Madeleine, Nyberg, Jenny, Leigh, Lucy, Gustavsson, Sara, Attia, John, Oldmeadow, Christopher, Ilicic, Marina, Linden, Thomas, Åberg, N. David, Levi, Chris, Spratt, Neil, Carey, Leeanne M., Pollack, Michael, Johnson, Sarah J., Kuhn, Georg Hans, Walker, Frederick R., Nilsson, Michael
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/163263
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spelling sg-ntu-dr.10356-1632632023-03-05T16:52:54Z Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries Hinwood, Madeleine Nyberg, Jenny Leigh, Lucy Gustavsson, Sara Attia, John Oldmeadow, Christopher Ilicic, Marina Linden, Thomas Åberg, N. David Levi, Chris Spratt, Neil Carey, Leeanne M. Pollack, Michael Johnson, Sarah J. Kuhn, Georg Hans Walker, Frederick R. Nilsson, Michael Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Cohort Analysis Dementia Introduction: The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. Methods and analysis: This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. Ethics and dissemination: This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals. Published version This work was supported by grants from the National Health and Medical Research Council (G2000554) and the Hunter Medical Research Institute (G2100140). 2022-11-30T00:18:52Z 2022-11-30T00:18:52Z 2022 Journal Article Hinwood, M., Nyberg, J., Leigh, L., Gustavsson, S., Attia, J., Oldmeadow, C., Ilicic, M., Linden, T., Åberg, N. D., Levi, C., Spratt, N., Carey, L. M., Pollack, M., Johnson, S. J., Kuhn, G. H., Walker, F. R. & Nilsson, M. (2022). Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries. BMJ Open, 12(5), e058244-. https://dx.doi.org/10.1136/bmjopen-2021-058244 2044-6055 https://hdl.handle.net/10356/163263 10.1136/bmjopen-2021-058244 35534077 2-s2.0-85129560525 5 12 e058244 en BMJ Open © Author(s) (or their employer(s)) 2022. Published by BMJ. Open access. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Cohort Analysis
Dementia
spellingShingle Science::Medicine
Cohort Analysis
Dementia
Hinwood, Madeleine
Nyberg, Jenny
Leigh, Lucy
Gustavsson, Sara
Attia, John
Oldmeadow, Christopher
Ilicic, Marina
Linden, Thomas
Åberg, N. David
Levi, Chris
Spratt, Neil
Carey, Leeanne M.
Pollack, Michael
Johnson, Sarah J.
Kuhn, Georg Hans
Walker, Frederick R.
Nilsson, Michael
Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
description Introduction: The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. Methods and analysis: This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. Ethics and dissemination: This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Hinwood, Madeleine
Nyberg, Jenny
Leigh, Lucy
Gustavsson, Sara
Attia, John
Oldmeadow, Christopher
Ilicic, Marina
Linden, Thomas
Åberg, N. David
Levi, Chris
Spratt, Neil
Carey, Leeanne M.
Pollack, Michael
Johnson, Sarah J.
Kuhn, Georg Hans
Walker, Frederick R.
Nilsson, Michael
format Article
author Hinwood, Madeleine
Nyberg, Jenny
Leigh, Lucy
Gustavsson, Sara
Attia, John
Oldmeadow, Christopher
Ilicic, Marina
Linden, Thomas
Åberg, N. David
Levi, Chris
Spratt, Neil
Carey, Leeanne M.
Pollack, Michael
Johnson, Sarah J.
Kuhn, Georg Hans
Walker, Frederick R.
Nilsson, Michael
author_sort Hinwood, Madeleine
title Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
title_short Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
title_full Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
title_fullStr Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
title_full_unstemmed Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
title_sort do p2y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? protocol for a target trial using multiple national swedish registries
publishDate 2022
url https://hdl.handle.net/10356/163263
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