Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study
Introduction Proton pump inhibitors (PPIs) are widely used for primary and secondary prevention of upper gastrointestinal bleeding. However, there remains controversy about the overall net clinical benefit of PPIs (omeprazole, rabeprazole, pantoprazole, lansoprazole) when coprescribed with direct or...
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BMJ Publishing Group
2022-06-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/6/e057991.full |
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| author | Lehana Thabane Lawrence Mbuagbaw Michael Paterson Laura Targownik Mei Wang Anne Holbrook Deborah Siegal |
| author_facet | Lehana Thabane Lawrence Mbuagbaw Michael Paterson Laura Targownik Mei Wang Anne Holbrook Deborah Siegal |
| author_sort | Lehana Thabane |
| collection | DOAJ |
| description | Introduction Proton pump inhibitors (PPIs) are widely used for primary and secondary prevention of upper gastrointestinal bleeding. However, there remains controversy about the overall net clinical benefit of PPIs (omeprazole, rabeprazole, pantoprazole, lansoprazole) when coprescribed with direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxaban). Our objective is to explore the risk of clinically relevant events, including bleeding, thromboembolic events and death, in patients prescribed DOACs while taking PPIs versus no PPI.Methods and analysis The protocol describes a retrospective cohort study of all Ontario residents aged 66 years or older with atrial fibrillation and at least one pharmacy dispensation for a DOAC identified using linked administrative healthcare databases covering 2009–2020. Ontario drug benefit dispensation records will be used to ascertain PPI exposure during DOAC therapy. The primary outcome is a composite of clinically relevant bleeding, thrombotic events or all-cause death. A minimum of 520 patients in total with at least one of the components of the composite outcome are needed. Poisson regression with a generalised estimating equation model will be used to calculate the adjusted incidence rate difference, incidence rate ratios 95% CI, adjusting for propensity for PPI use using inverse probability of treatment weights.Ethics and dissemination This research is exempt from REB review under section 45 of Ontario’s Personal Health Information Protection Act. We will report our findings in a peer-reviewed biomedical journal and present them at conferences. The study will provide useful evidence to optimise the coprescription of DOACs and PPIs in practice. |
| format | Article |
| id | doaj-art-e299a5e22abf43f998be541413048ef4 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-e299a5e22abf43f998be541413048ef42025-01-28T08:25:09ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2021-057991Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort studyLehana Thabane0Lawrence Mbuagbaw1Michael Paterson2Laura Targownik3Mei Wang4Anne Holbrook5Deborah Siegal6Biostatistics Unit, Research Institute of St. Joseph`s Hamilton, Hamilton, Ontario, Canadaassociate professorInstitute for Clinical Evaluative Sciences, Toronto, Ontario, CanadaHealth Sciences Centre Winnipeg, Winnipeg, Manitoba, CanadaTongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDivision of Clinical Pharmacology and Toxicology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada17 Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, CanadaIntroduction Proton pump inhibitors (PPIs) are widely used for primary and secondary prevention of upper gastrointestinal bleeding. However, there remains controversy about the overall net clinical benefit of PPIs (omeprazole, rabeprazole, pantoprazole, lansoprazole) when coprescribed with direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban, edoxaban). Our objective is to explore the risk of clinically relevant events, including bleeding, thromboembolic events and death, in patients prescribed DOACs while taking PPIs versus no PPI.Methods and analysis The protocol describes a retrospective cohort study of all Ontario residents aged 66 years or older with atrial fibrillation and at least one pharmacy dispensation for a DOAC identified using linked administrative healthcare databases covering 2009–2020. Ontario drug benefit dispensation records will be used to ascertain PPI exposure during DOAC therapy. The primary outcome is a composite of clinically relevant bleeding, thrombotic events or all-cause death. A minimum of 520 patients in total with at least one of the components of the composite outcome are needed. Poisson regression with a generalised estimating equation model will be used to calculate the adjusted incidence rate difference, incidence rate ratios 95% CI, adjusting for propensity for PPI use using inverse probability of treatment weights.Ethics and dissemination This research is exempt from REB review under section 45 of Ontario’s Personal Health Information Protection Act. We will report our findings in a peer-reviewed biomedical journal and present them at conferences. The study will provide useful evidence to optimise the coprescription of DOACs and PPIs in practice.https://bmjopen.bmj.com/content/12/6/e057991.full |
| spellingShingle | Lehana Thabane Lawrence Mbuagbaw Michael Paterson Laura Targownik Mei Wang Anne Holbrook Deborah Siegal Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study BMJ Open |
| title | Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study |
| title_full | Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study |
| title_fullStr | Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study |
| title_full_unstemmed | Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study |
| title_short | Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study |
| title_sort | association of direct oral anticoagulant proton pump inhibitor cotherapy with adverse outcomes protocol for a population based cohort study |
| url | https://bmjopen.bmj.com/content/12/6/e057991.full |
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