{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T01:16:48Z","timestamp":1776302208632,"version":"3.50.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Daiichi Sankyo Co., Ltd."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The real-world status of proton pump inhibitor (PPI) use in patients with atrial fibrillation (AF) receiving antithrombotic treatment is largely unknown. The All Nippon AF In the Elderly (ANAFIE) Registry, a prospective, multicenter, observational study, aimed to determine treatment patterns, risk factors, and outcomes among elderly (aged \u226575 years) Japanese non-valvular AF (NVAF) patients in the real-world clinical setting. The present subanalysis of the ANAFIE Registry determined the PPI prescription status of 32,490 elderly Japanese NVAF patients. Patients were stratified by PPI use (PPI+) or no PPI use (PPI\u2212). Risk scores for stroke (CHADS<jats:sub>2<\/jats:sub>, CHA<jats:sub>2<\/jats:sub>DS<jats:sub>2<\/jats:sub>-VASc) and bleeding (HAS-BLED), anticoagulant use, time in therapeutic range (TTR) for warfarin, and anticoagulant\/antiplatelet combination use were evaluated. PPIs were used in 11,981 (36.9%) patients. Compared with the PPI\u2212 group, the PPI+ group included a greater proportion of female patients (45.2% vs 41.3%; <jats:italic>P<\/jats:italic> &lt;0.0001) and had significantly higher CHADS<jats:sub>2<\/jats:sub>, CHA<jats:sub>2<\/jats:sub>DS<jats:sub>2<\/jats:sub>-VASc, and HAS-BLED scores (<jats:italic>P<\/jats:italic> &lt;0.0001 for each) as well as higher prevalences of several comorbidities. In the PPI+ group, 54.6% of patients did not have gastrointestinal (GI) disorders and were likely prescribed a PPI to prevent GI bleeding events. Most of the patients with a GI disorder in the PPI+ group had reflux esophagitis. Compared with patients not receiving anticoagulants, a significantly higher proportion of patients receiving anticoagulants received PPIs. For patients receiving anticoagulants, antiplatelet drugs, and both drugs, rates of PPI use were 34.1%, 44.1%, and 53.5%, respectively (P &lt;0.01). Although the rate of PPI use was the highest for NVAF patients receiving both antiplatelet and anticoagulants, no clear differences were observed in the anticoagulants used. These data suggest that PPIs were actively prescribed in high-risk cases and may have been used to prevent GI bleeding among elderly NVAF patients receiving antithrombotic drugs.<\/jats:p>\n<jats:p><jats:bold>Trial registration:<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/UMIN000024006\" xlink:type=\"simple\">UMIN000024006<\/jats:ext-link><\/jats:p>","DOI":"10.1371\/journal.pone.0240859","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T18:51:02Z","timestamp":1604602262000},"page":"e0240859","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Current status of proton pump inhibitor use in Japanese elderly patients with non-valvular atrial fibrillation: A subanalysis of the ANAFIE Registry"],"prefix":"10.1371","volume":"15","author":[{"given":"Yuji","family":"Mizokami","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-823X","authenticated-orcid":true,"given":"Takatsugu","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotsugu","family":"Atarashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaharu","family":"Akao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Koretsune","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Okumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Tsutsui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunori","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Hirayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Yasaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takenori","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Teramukai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jumpei","family":"Kaburagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Takita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"pone.0240859.ref001","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1136\/heartjnl-2018-313350","article-title":"Global rising trends of atrial fibrillation: a major public health concern","volume":"104","author":"NJ Patel","year":"2018","journal-title":"Heart"},{"key":"pone.0240859.ref002","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.jacc.2006.10.062","article-title":"Mortality trends in patients diagnosed with first atrial fibrillation: a 21-year community-based study","volume":"49","author":"Y Miyasaka","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"pone.0240859.ref003","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1161\/01.STR.22.8.983","article-title":"Atrial fibrillation as an independent risk factor for stroke: the Framingham Study","volume":"22","author":"PA Wolf","year":"1991","journal-title":"Stroke"},{"key":"pone.0240859.ref004","doi-asserted-by":"crossref","first-page":"e0191592","DOI":"10.1371\/journal.pone.0191592","article-title":"Risk factors for death, stroke, and bleeding in 28,628 patients from the GARFIELD-AF registry: Rationale for comprehensive management of atrial fibrillation","volume":"13","author":"JP Bassand","year":"2018","journal-title":"PLoS One"},{"key":"pone.0240859.ref005","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1136\/heartjnl-2019-314898","article-title":"Stroke and thromboembolism prevention in atrial fibrillation","volume":"106","author":"S Jame","year":"2020","journal-title":"Heart"},{"key":"pone.0240859.ref006","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0140-6736(13)62343-0","article-title":"Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials","volume":"383","author":"CT Ruff","year":"2014","journal-title":"Lancet"},{"key":"pone.0240859.ref007","doi-asserted-by":"crossref","first-page":"857","DOI":"10.7326\/0003-4819-146-12-200706190-00007","article-title":"Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation","volume":"146","author":"RG Hart","year":"2007","journal-title":"Ann Intern Med"},{"key":"pone.0240859.ref008","doi-asserted-by":"crossref","first-page":"761","DOI":"10.7556\/jaoa.2017.148","article-title":"Role of antiplatelet therapy in stroke prevention in patients with atrial fibrillation","volume":"117","author":"R Manaktala","year":"2017","journal-title":"J Am Osteopath Assoc"},{"key":"pone.0240859.ref009","first-page":"49","article-title":"Atrial fibrillation in the elderly","volume":"16","author":"P D\u00edez-Villanueva","year":"2019","journal-title":"J Geriatr Cardiol"},{"key":"pone.0240859.ref010","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/clc.23293","article-title":"Impact of age on thromboembolic events in patients with non-valvular atrial fibrillation","volume":"43","author":"YG Kim","year":"2020","journal-title":"Clin Cardiol"},{"key":"pone.0240859.ref011","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/ageing\/afv071","article-title":"Impact of advanced age on management and prognosis in atrial fibrillation: insights from a population\u2010based study in general practice","volume":"44","author":"A Wolff","year":"2015","journal-title":"Age Ageing"},{"key":"pone.0240859.ref012","doi-asserted-by":"crossref","first-page":"e005657","DOI":"10.1161\/JAHA.117.005657","article-title":"Thromboembolic risk, bleeding outcomes and effect of different antithrombotic strategies in very elderly patients with atrial fibrillation: A sub-analysis from the PREFER in AF (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation).","volume":"6","author":"G Patti","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"pone.0240859.ref013","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1080\/03007995.2017.1411793","article-title":"Comparison of major bleeding risk in patients with non-valvular atrial fibrillation receiving direct oral anticoagulants in the real-world setting: a network meta-analysis","volume":"34","author":"S Deitelzweig","year":"2018","journal-title":"Curr Med Res Opin"},{"key":"pone.0240859.ref014","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.cjca.2019.02.009","article-title":"Stroke prevention, evaluation of bleeding risk, and anticoagulant treatment management in atrial fibrillation contemporary international guidelines","volume":"35","author":"M Proietti","year":"2019","journal-title":"Can J Cardiol"},{"key":"pone.0240859.ref015","doi-asserted-by":"crossref","first-page":"E554","DOI":"10.3390\/jcm8040554","article-title":"Effectiveness and safety of direct oral anticoagulants versus vitamin K antagonists for people aged 75 years and over with atrial fibrillation: A systematic review and meta-analyses of observational studies","volume":"8","author":"A Mitchell","year":"2019","journal-title":"J Clin Med"},{"key":"pone.0240859.ref016","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.amjmed.2018.12.023","article-title":"Comparative stroke, bleeding, and mortality risks in older medicare patients treated with oral anticoagulants for nonvalvular atrial fibrillation","volume":"132","author":"DJ Graham","year":"2019","journal-title":"Am J Med"},{"key":"pone.0240859.ref017","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1111\/jgh.14701","article-title":"Use of direct oral anticoagulant in atrial fibrillation with gastrointestinal bleeding: Balancing gastrointestinal safety and cardiovascular risks","volume":"34","author":"JJ Sung","year":"2019","journal-title":"J Gastroenterol Hepatol"},{"key":"pone.0240859.ref018","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.thromres.2019.01.020","article-title":"Resumption of anticoagulant therapy after anticoagulant-related gastrointestinal bleeding: A systematic review and meta-analysis","volume":"175","author":"D Little","year":"2019","journal-title":"Thromb Res"},{"key":"pone.0240859.ref019","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.amjmed.2009.07.036","article-title":"Review: treatment of gastroesophageal reflux disease in the elderly","volume":"123","author":"CH Poh","year":"2010","journal-title":"Am J Med"},{"key":"pone.0240859.ref020","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2147\/JPR.S156938","article-title":"Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits","volume":"11","author":"KA Gwee","year":"2018","journal-title":"J Pain Res"},{"key":"pone.0240859.ref021","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1001\/jama.2018.17242","article-title":"Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding","volume":"320","author":"WA Ray","year":"2018","journal-title":"JAMA"},{"key":"pone.0240859.ref022","doi-asserted-by":"crossref","first-page":"e015735","DOI":"10.1136\/bmjopen-2016-015735","article-title":"Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans","volume":"7","author":"Y Xie","year":"2017","journal-title":"BMJ Open"},{"key":"pone.0240859.ref023","doi-asserted-by":"crossref","first-page":"l1580","DOI":"10.1136\/bmj.l1580","article-title":"Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study","volume":"365","author":"Y Xie","year":"2019","journal-title":"BMJ"},{"key":"pone.0240859.ref024","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jjcc.2018.02.018","article-title":"Prospective observational study in elderly patients with non-valvular atrial fibrillation: Rationale and design of the All Nippon AF In the Elderly (ANAFIE) Registry.","volume":"72","author":"H Inoue","year":"2018","journal-title":"J Cardiol"},{"key":"pone.0240859.ref025","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1253\/circj.CJ-19-0094","article-title":"Baseline Demographics and Clinical Characteristics in the All Nippon AF in the Elderly (ANAFIE) Registry.","volume":"83","author":"Y Koretsune","year":"2019","journal-title":"Circ J."},{"key":"pone.0240859.ref026","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S0140-6736(17)30770-5","article-title":"Rothwell PM; Oxford Vascular Study. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study","volume":"390","author":"L Li","year":"2017","journal-title":"Lancet"},{"key":"pone.0240859.ref027","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.1365-2036.2008.03780.x","article-title":"Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study","volume":"28","author":"EL Mass\u00f3 Gonz\u00e1lez","year":"2008","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0240859.ref028","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/FJC.0000000000000684","article-title":"Prophylactic use of mucosal protective agents and proton pump inhibitors in patients undergoing percutaneous coronary intervention: Real world evidences of 36,870 patients","volume":"74","author":"YH Li","year":"2019","journal-title":"J Cardiovasc Pharmacol"},{"key":"pone.0240859.ref029","first-page":"CD011785","article-title":"Pharmacological interventions for prevention and treatment of upper gastrointestinal bleeding in newborn infants","volume":"7","author":"DS Green","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"pone.0240859.ref030","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S2468-1253(18)30037-2","article-title":"Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials","volume":"3","author":"B Scally","year":"2018","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"pone.0240859.ref031","doi-asserted-by":"crossref","first-page":"e2903","DOI":"10.1097\/MD.0000000000002903","article-title":"Proton pump inhibitor therapy is associated with reduction of early bleeding risk after prophylactic endoscopic variceal band ligation: A retrospective cohort study","volume":"95","author":"SH Kang","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"pone.0240859.ref032","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/ehjcvp\/pvy030","article-title":"Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry","volume":"5","author":"NPG Hoedemaker","year":"2019","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"pone.0240859.ref033","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1097\/MEG.0000000000001125","article-title":"Reduction in postpercutaneous coronary intervention angina in addition to gastrointestinal events in patients on combined proton pump inhibitors and dual antiplatelet therapy: a systematic review and meta-analysis","volume":"30","author":"MY Khan","year":"2018","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"pone.0240859.ref034","article-title":"Costs of bleeding on long-term antiplatelet treatment without routine co-prescription of proton-pump inhibitors","author":"Oxford Vascular Study","year":"2019","journal-title":"Int J Stroke"},{"key":"pone.0240859.ref035","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.2165\/00003495-200363240-00004","article-title":"Clinical pharmacology of proton pump inhibitors: what the practising physician needs to know","volume":"63","author":"M Robinson","year":"2003","journal-title":"Drugs"},{"key":"pone.0240859.ref036","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1001\/jama.2009.261","article-title":"Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome","volume":"301","author":"PM Ho","year":"2009","journal-title":"JAMA"},{"key":"pone.0240859.ref037","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1111\/j.1538-7836.2006.02162.x","article-title":"Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin","volume":"4","author":"M Gilard","year":"2006","journal-title":"J Thromb Haemost"},{"key":"pone.0240859.ref038","doi-asserted-by":"crossref","first-page":"e13382","DOI":"10.1111\/ijcp.13382","article-title":"Proton pump inhibitors co-prescribed with warfarin reduce warfarin control as measured by time in therapeutic range","volume":"73","author":"V Bertram","year":"2019","journal-title":"Int J Clin Pract"},{"key":"pone.0240859.ref039","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s00535-017-1369-3","article-title":"Magnitude and direction of the association between Clostridium difficile infection and proton pump inhibitors in adults and pediatric patients: a systematic review and meta-analysis","volume":"53","author":"T Oshima","year":"2018","journal-title":"J Gastroenterol"},{"key":"pone.0240859.ref040","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/apt.13568","article-title":"A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors","volume":"43","author":"AG Clooney","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0240859.ref041","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.2217\/fmb-2018-0157","article-title":"Vulnerability of long-term care facility residents to Clostridium difficile infection due to microbiome disruptions","volume":"13","author":"BB Fuchs","year":"2018","journal-title":"Future Microbiol"},{"key":"pone.0240859.ref042","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.anaerobe.2014.08.007","article-title":"Clostridium difficile infection in elderly nursing home residents","volume":"30","author":"C Rodriguez","year":"2014","journal-title":"Anaerobe"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0240859","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T18:51:16Z","timestamp":1604602276000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0240859"}},"subtitle":[],"editor":[{"given":"Tomohiko","family":"Ai","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,5]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0240859","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,5]]}}}