Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context
Summary: Background: Fluoroquinolones (FQs) are commonly used to treat urinary tract infections (UTIs), but some studies have suggested they may increase the risk of aortic aneurysm or dissection (AA/AD). However, no large-scale international study has thoroughly assessed this risk. Methods: A retr...
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2025-03-01
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| author | Jack L. Janetzki Jung Ho Kim Evan Minty Jung Ah Lee Daniel R. Morales Rohan Khera Chungsoo Kim Thamir M. Alshammari Scott L. DuVall Michael E. Matheny Thomas Falconer Seonji Kim Thanh-Phuc Phan Phung-Anh Nguyen Min-Huei Hsu Jason C. Hsu Rae Woong Park Kenneth K.C. Man Sarah Seager Mui Van Zandt James P. Gilbert Patrick B. Ryan Martijn J. Schuemie Marc A. Suchard George Hripcsak Nicole Pratt Seng Chan You |
| author_facet | Jack L. Janetzki Jung Ho Kim Evan Minty Jung Ah Lee Daniel R. Morales Rohan Khera Chungsoo Kim Thamir M. Alshammari Scott L. DuVall Michael E. Matheny Thomas Falconer Seonji Kim Thanh-Phuc Phan Phung-Anh Nguyen Min-Huei Hsu Jason C. Hsu Rae Woong Park Kenneth K.C. Man Sarah Seager Mui Van Zandt James P. Gilbert Patrick B. Ryan Martijn J. Schuemie Marc A. Suchard George Hripcsak Nicole Pratt Seng Chan You |
| author_sort | Jack L. Janetzki |
| collection | DOAJ |
| description | Summary: Background: Fluoroquinolones (FQs) are commonly used to treat urinary tract infections (UTIs), but some studies have suggested they may increase the risk of aortic aneurysm or dissection (AA/AD). However, no large-scale international study has thoroughly assessed this risk. Methods: A retrospective cohort study was conducted using a large, distributed network analysis across 14 databases from 5 countries (United States, South Korea, Japan, Taiwan, and Australia). The study included 13,588,837 patients aged 35 or older who initiated systemic fluoroquinolones (FQs) or comparable antibiotics (trimethoprim with or without sulfamethoxazole [TMP] or cephalosporins [CPHs]) for UTI treatment in the outpatient setting between JAN 01, 2010 and DEC 31, 2019. Patients were included if at the index date they had at least 365 days of prior observation and were not hospitalised for any reason on or within 7 days prior to the index date. The primary outcome was AA/AD occurrence within 60 days of exposure, with secondary outcomes examining AA and AD separately. Cox proportional hazards models with 1:1 propensity score (PS) matching were used to estimate the risk, with results calibrated using negative control outcomes. Analyses were subjected to pre-defined study diagnostics, and only those passing all diagnostics were reported. Hazard ratios (HRs) were pooled using Bayesian random-effects meta-analysis. Findings: Among analyses that passed diagnostics there were 1,954,798 and 1,195,962 propensity-matched pairs for the FQ versus TMP and FQ versus CPH comparisons respectively. For the 60-day follow-up there was no difference in risk of AA/AD between FQ and TMP (absolute rate difference [ARD], 0.21 per 1000 person-year; calibrated HR, 0.91 [95% CI 0.73–1.10]). There was no significant difference in risk for FQ versus CPH (ARD, 0.11 per 1000 person-year; calibrated HR, 1.01 [95% CI 0.82–1.25]). Interpretation: This large-scale study used a rigorous design with objective diagnostics to address bias and confounding. There was no increased risk of AA/AD associated with FQ compared to TMP or CPH in patients treated for UTI in the outpatient setting. As we only examined FQ used to treat UTIs in the outpatient setting, the results may not be generalisable to other indications with different severity. Funding: Yonsei University College of Medicine, Government-wide R&D Fund project for infectious disease research (GFID), Republic of Korea, National Health and Medical Research Council (NHMRC) Australian Government. Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), Department of Veterans Affairs, the United States Government. |
| format | Article |
| id | doaj-art-3f7e837189ec4306b205d32ca15b6efc |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-3f7e837189ec4306b205d32ca15b6efc2025-02-02T05:29:11ZengElsevierEClinicalMedicine2589-53702025-03-0181103096Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in contextJack L. Janetzki0Jung Ho Kim1Evan Minty2Jung Ah Lee3Daniel R. Morales4Rohan Khera5Chungsoo Kim6Thamir M. Alshammari7Scott L. DuVall8Michael E. Matheny9Thomas Falconer10Seonji Kim11Thanh-Phuc Phan12Phung-Anh Nguyen13Min-Huei Hsu14Jason C. Hsu15Rae Woong Park16Kenneth K.C. Man17Sarah Seager18Mui Van Zandt19James P. Gilbert20Patrick B. Ryan21Martijn J. Schuemie22Marc A. Suchard23George Hripcsak24Nicole Pratt25Seng Chan You26Clinical and Health Sciences, Quality Use of Medicines and Pharmacy Research Centre, University of South Australia, Adelaide, AustraliaDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, South KoreaDepartment of Medicine, University of Calgary, Calgary, CanadaDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, South KoreaDivision of Population Health and Genomics, University of Dundee, Dundee, United KingdomSection of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, USASection of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, USADepartment of Clinical Pharmacy, Pharmacy Practice Research Unit, Faculty of Pharmacy, Jazan University, Jazan, Saudi ArabiaVA Informatics and Computing Infrastructure, United States Department of Veterans Affairs, Salt Lake City, USATennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, USADepartment of Biomedical Informatics, Columbia University, New York, USADepartment of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South KoreaInternational Ph.D. Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, New Taipei City, TaiwanClinical Data Center, Office of Data Science, Taipei Medical University, New Taipei City, TaiwanGraduate Institute of Data Science, College of Management, Taipei Medical University, Taipei City, TaiwanClinical Data Center, Office of Data Science, Taipei Medical University, New Taipei City, TaiwanDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon, South KoreaSchool of Pharmacy, University College London, London, United KingdomIQVIA, Cambridge, MA, USAIQVIA, Cambridge, MA, USAJanssen Research and Development, Titusville, USAEpidemiology, Johnson & Johnson, Titusville, USAEpidemiology, Johnson & Johnson, Titusville, USADepartment of Biostatistics, University of California, Los Angeles, USADepartment of Biomedical Informatics, Columbia University, New York, USAClinical and Health Sciences, Quality Use of Medicines and Pharmacy Research Centre, University of South Australia, Adelaide, AustraliaDepartment of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea; Corresponding author. Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.Summary: Background: Fluoroquinolones (FQs) are commonly used to treat urinary tract infections (UTIs), but some studies have suggested they may increase the risk of aortic aneurysm or dissection (AA/AD). However, no large-scale international study has thoroughly assessed this risk. Methods: A retrospective cohort study was conducted using a large, distributed network analysis across 14 databases from 5 countries (United States, South Korea, Japan, Taiwan, and Australia). The study included 13,588,837 patients aged 35 or older who initiated systemic fluoroquinolones (FQs) or comparable antibiotics (trimethoprim with or without sulfamethoxazole [TMP] or cephalosporins [CPHs]) for UTI treatment in the outpatient setting between JAN 01, 2010 and DEC 31, 2019. Patients were included if at the index date they had at least 365 days of prior observation and were not hospitalised for any reason on or within 7 days prior to the index date. The primary outcome was AA/AD occurrence within 60 days of exposure, with secondary outcomes examining AA and AD separately. Cox proportional hazards models with 1:1 propensity score (PS) matching were used to estimate the risk, with results calibrated using negative control outcomes. Analyses were subjected to pre-defined study diagnostics, and only those passing all diagnostics were reported. Hazard ratios (HRs) were pooled using Bayesian random-effects meta-analysis. Findings: Among analyses that passed diagnostics there were 1,954,798 and 1,195,962 propensity-matched pairs for the FQ versus TMP and FQ versus CPH comparisons respectively. For the 60-day follow-up there was no difference in risk of AA/AD between FQ and TMP (absolute rate difference [ARD], 0.21 per 1000 person-year; calibrated HR, 0.91 [95% CI 0.73–1.10]). There was no significant difference in risk for FQ versus CPH (ARD, 0.11 per 1000 person-year; calibrated HR, 1.01 [95% CI 0.82–1.25]). Interpretation: This large-scale study used a rigorous design with objective diagnostics to address bias and confounding. There was no increased risk of AA/AD associated with FQ compared to TMP or CPH in patients treated for UTI in the outpatient setting. As we only examined FQ used to treat UTIs in the outpatient setting, the results may not be generalisable to other indications with different severity. Funding: Yonsei University College of Medicine, Government-wide R&D Fund project for infectious disease research (GFID), Republic of Korea, National Health and Medical Research Council (NHMRC) Australian Government. Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), Department of Veterans Affairs, the United States Government.http://www.sciencedirect.com/science/article/pii/S2589537025000288FluoroquinoloneObservational studyAortic dissectionAortic aneurysm |
| spellingShingle | Jack L. Janetzki Jung Ho Kim Evan Minty Jung Ah Lee Daniel R. Morales Rohan Khera Chungsoo Kim Thamir M. Alshammari Scott L. DuVall Michael E. Matheny Thomas Falconer Seonji Kim Thanh-Phuc Phan Phung-Anh Nguyen Min-Huei Hsu Jason C. Hsu Rae Woong Park Kenneth K.C. Man Sarah Seager Mui Van Zandt James P. Gilbert Patrick B. Ryan Martijn J. Schuemie Marc A. Suchard George Hripcsak Nicole Pratt Seng Chan You Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context EClinicalMedicine Fluoroquinolone Observational study Aortic dissection Aortic aneurysm |
| title | Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context |
| title_full | Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context |
| title_fullStr | Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context |
| title_full_unstemmed | Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context |
| title_short | Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort studyResearch in context |
| title_sort | risk of aortic aneurysm or dissection following use of fluoroquinolones a retrospective multinational network cohort studyresearch in context |
| topic | Fluoroquinolone Observational study Aortic dissection Aortic aneurysm |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025000288 |
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