{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:55:03Z","timestamp":1781585703952,"version":"3.54.5"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-vitamin K antagonist oral anticoagulants (NOACs) are widely prescribed for stroke prevention in atrial fibrillation (AF). Although they reduce intracranial hemorrhage compared with warfarin, gastrointestinal bleeding (GIB), particularly upper GIB (UGIB), remains a clinically significant complication. Proton pump inhibitors (PPIs) are frequently co-prescribed for gastroprotection, yet the available evidence remains largely observational and subject to methodological heterogeneity and confounding by indication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence base and review methodology<\/jats:title>\n                    <jats:p>We conducted a structured narrative review of nationwide cohort studies, multi-database analyses, randomized trials, and meta-analyses evaluating PPI co-therapy in NOAC-treated populations, with emphasis on clinically adjudicated UGIB outcomes and methodological considerations including confounding by indication and endpoint variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical evidence and implications for cardiac rhythmology practice<\/jats:title>\n                    <jats:p>A large Korean nationwide cohort demonstrated that PPI co-therapy in NOAC-treated AF patients was associated with reduced risks of UGIB hospitalization (weighted HR 0.825) and transfusion-requiring UGIB (weighted HR 0.798), particularly in high-risk subgroups. A meta-analysis of approximately 1.97 million oral anticoagulant users reported lower odds of total and major GIB with PPI use (OR \u223c0.67\u20130.68). Randomized evidence suggests biological plausibility for reduction of gastroduodenal bleeding but highlights endpoint specificity. However, heterogeneity across analytic designs underscores persistent residual confounding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PPI co-therapy may represent a clinically pragmatic strategy pending dedicated randomized evidence in high-risk NOAC-treated patients. A pragmatic, risk-stratified approach appears most appropriate while awaiting confirmation from dedicated randomized trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1816099","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:27:28Z","timestamp":1781584048000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Proton pump inhibitor co-therapy in patients receiving non-vitamin K antagonist oral anticoagulants: current evidence, gastrointestinal bleeding prevention, and clinical considerations"],"prefix":"10.3389","volume":"13","author":[{"given":"Dong-Hyeok","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Cardiology, Ewha Womans University Seoul Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeji","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ewha Womans University Seoul Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ewha Womans University Mokdong Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongmin","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ewha Womans University Mokdong Hospital","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbeom","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Ewha Womans University Mokdong Hospital","place":["Seoul, Republic of 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