{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:09:53Z","timestamp":1785409793403,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002635","name":"Inha University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002635","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01easw929","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Health and Welfare","award":["RS-2023-00265440"],"award-info":[{"award-number":["RS-2023-00265440"]}]},{"award":["RS-2023-00265440"],"award-info":[{"award-number":["RS-2023-00265440"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: Proton pump inhibitors are commonly used during oral anticoagulant therapy in patients with atrial fibrillation, but evidence regarding outcomes beyond upper gastrointestinal bleeding remains limited. We evaluated whether concomitant proton pump inhibitor use during oral anticoagulant therapy was associated with thromboembolic events, bleeding outcomes, and all-cause mortality. Methods: This retrospective multicenter cohort study included patients with atrial fibrillation who initiated oral anticoagulant therapy. Concomitant proton pump inhibitor use was modeled as a time-varying exposure with a prespecified 7-day lag. The primary outcome was a composite of thromboembolic events, major bleeding, and all-cause mortality. Secondary outcomes included each component outcome and gastrointestinal bleeding. Associations were estimated using time-dependent Cox proportional hazard models after multiple imputation of missing baseline variables. Results: Among 11,203 patients (median age 71 years [interquartile range 62\u201378]; 4743 women [42.3%]), 7-day lagged time-varying proton pump inhibitor exposure was associated with a higher risk of the composite outcome (hazard ratio 1.29, 95% confidence interval 1.08\u20131.55), major bleeding (1.80, 1.36\u20132.37), gastrointestinal bleeding (1.77, 1.18\u20132.66), and all-cause mortality (1.58, 1.00\u20132.48). No statistically significant association was observed for thromboembolic events. Across robustness analyses, the overall pattern was broadly maintained, although estimates varied according to exposure timing. Conclusions: In this observational cohort of patients with atrial fibrillation receiving oral anticoagulant therapy, concomitant proton pump inhibitor use modeled with a 7-day lagged time-varying framework was associated with higher risks of several bleeding-related outcomes and all-cause mortality, but not thromboembolism. These findings should be interpreted as associations rather than causal effects.<\/jats:p>","DOI":"10.3390\/jcm15103590","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T19:10:52Z","timestamp":1778267452000},"page":"3590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proton Pump Inhibitor Use and Clinical Outcomes in Atrial Fibrillation During Anticoagulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Do-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Cardiology, Ajou University School of Medicine, World Cup-ro 164, Yeongtong-gu, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-3667","authenticated-orcid":false,"given":"Hye Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Sanggye-Paik Hospital, Inje University College of Medicine, Dongil-ro 1342, Nowon-gu, Seoul 01757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen Laurel","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hanyang University Hospital, Wangsimni-ro 222-1, Seongdong-gu, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Young","family":"Roh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Gurodong-ro 148, Guro-gu, Seoul 08308, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7430-415X","authenticated-orcid":false,"given":"Kwang-No","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ajou University School of Medicine, World Cup-ro 164, Yeongtong-gu, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1093\/eurheartj\/ehae176","article-title":"2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)","volume":"45","author":"Rienstra","year":"2024","journal-title":"Eur. 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Pharm."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T04:21:08Z","timestamp":1778386868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":20,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcm15103590"],"URL":"https:\/\/doi.org\/10.3390\/jcm15103590","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]}}}