{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T04:02:53Z","timestamp":1754020973192,"version":"3.40.5"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cathet Cardio Intervent"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Several studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and\/or aspirin, possibly leading to cardiovascular events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>We aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23\u2010month ticagrelor monotherapy following 1\u2010month dual antiplatelet therapy [DAPT]) with the reference arm (12\u2010month aspirin monotherapy following 12\u2010month DAPT) after PCI. Patient\u2010oriented composite endpoints (POCEs: all\u2010cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time\u2010dependent covariate in patients with the experiment or reference antiplatelet arm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio\u00a0[HR]: 1.27; 95% confidence interval\u00a0[CI]: 1.12\u20131.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92\u20131.19; <jats:italic>p<\/jats:italic><jats:sub>interaction<\/jats:sub>\u2009=\u20090.035). During the second\u2010year follow\u2010up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27\u20131.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83\u20131.28; <jats:italic>p<\/jats:italic><jats:sub>interaction<\/jats:sub>\u2009=\u20090.008).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p>URL: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\">https:\/\/clinicaltrials.gov<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1002\/ccd.30217","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T19:49:05Z","timestamp":1651520945000},"page":"72-82","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3919-5648","authenticated-orcid":false,"given":"Masafumi","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Heart Center University of Amsterdam Amsterdam The Netherlands"},{"name":"Interventional Medicine and Innovation National University of Ireland Galway (NUIG) Galway Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Onuma","sequence":"additional","affiliation":[{"name":"Interventional Medicine and Innovation National University of Ireland Galway (NUIG) Galway Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-1248","authenticated-orcid":false,"given":"Hideyuki","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Heart Center University of Amsterdam Amsterdam The Netherlands"},{"name":"Interventional Medicine and Innovation National University of Ireland Galway (NUIG) Galway Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Heart Center University of Amsterdam Amsterdam The Netherlands"},{"name":"Interventional Medicine and Innovation National University of Ireland Galway (NUIG) Galway Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0390-8060","authenticated-orcid":false,"given":"Chao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Department of Cardiology Xijing Hospital Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rutao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Department of Cardiology Xijing Hospital Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"O'Leary","sequence":"additional","affiliation":[{"name":"Interventional Medicine and Innovation National University of Ireland Galway (NUIG) Galway Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edouard","family":"Benit","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Critical Care Medicine Hartcentrum Hasselt, Jessa Ziekenhuis Hasselt Belgium"},{"name":"Faculty of Medicine and Life Sciences University of Hasselt Hasselt Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Janssens","sequence":"additional","affiliation":[{"name":"Imelda Ziekenhuis Bonheiden Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Ferrario","sequence":"additional","affiliation":[{"name":"Policlinico San Matteo Pavia 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Maria Terni Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Huber","sequence":"additional","affiliation":[{"name":"Wilhelminenspital Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Buszman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Silesian Medical School Katowice Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scot","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Cardiology Royal Blackburn Hospital Blackburn UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna J.","family":"Wykrzykowska","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Heart Center University of Amsterdam Amsterdam The Netherlands"},{"name":"University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan J.","family":"Piek","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Heart Center University of Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"J\u00fcni","sequence":"additional","affiliation":[{"name":"Applied Health Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Hamm","sequence":"additional","affiliation":[{"name":"University of Giessen and Kerckhoff Heartand Thorax Center University of Giessen Bad Nauheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Windecker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, 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