{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T15:15:01Z","timestamp":1781968501368,"version":"3.54.5"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2120"],"award-info":[{"award-number":["JPMJSP2120"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health, Labor, and Welfare","award":["22AA2003"],"award-info":[{"award-number":["22AA2003"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Takotsubo cardiomyopathy is characterized by temporary ballooning of the left ventricle and may lead to thrombosis, necessitating anticoagulation therapy in high-risk patients. However, no previous studies have compared anticoagulation therapies for this population. We aimed to compare the clinical outcomes of patients treated with direct oral anticoagulants (DOACs) and those treated with heparin. This retrospective study included patients with Takotsubo cardiomyopathy receiving DOACs or heparin within the first 2 days of admission between April 2012 and March 2021, identified from a nationwide in-hospital database in Japan. The primary outcome was in-hospital mortality. The secondary outcomes were ischemic and bleeding events, hospitalization costs, and length of hospital stay. After adjustment with propensity score-based inverse probability weighting, the risks of outcomes were estimated using Poisson regression models. Among 4,813 patients, 530 received DOACs and 4,283 received heparin. The DOAC group was older than the heparin group (mean [standard deviation] 78.1 [9.4] vs. 74.4 [11.2] years). After covariate adjustment, in-hospital mortality (4.0% vs. 3.8%; p\u2009=\u20090.87), ischemic events (1.1% vs. 2.8%; p\u2009=\u20090.067), and bleeding events (0.2% vs. 0.3%; p\u2009=\u20090.67) did not significantly differ between the DOAC and heparin groups. In contrast, the DOAC group had shorter hospital stays (median, 11 days vs. 13 days; p\u2009&lt;\u20090.001) and lower total hospitalization costs ($5,181 USD vs. $6,084 USD; p\u2009=\u20090.003). These findings provide clinicians with valuable insights regarding the use of DOACs for patients with Takotsubo cardiomyopathy.<\/jats:p>","DOI":"10.1371\/journal.pone.0336960","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:43:03Z","timestamp":1763059383000},"page":"e0336960","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of treatment outcomes of direct oral anticoagulants and heparin for patients with Takotsubo cardiomyopathy: A nationwide cohort analysis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-7448","authenticated-orcid":true,"given":"Sadahiro","family":"Hijikata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiko","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1894-0290","authenticated-orcid":true,"given":"Kiyohide","family":"Fushimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Sasano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"pone.0336960.ref001","first-page":"56","article-title":"Tako-tsubo like cardiomyopathy due to multivessel spasm","volume-title":"Clinical aspect of myocardial injury: From ischemia to heart failure","author":"H Sato","year":"1990"},{"issue":"12","key":"pone.0336960.ref002","first-page":"834","article-title":"Incidence, management, and prognostic impact of arrhythmias in patients with Takotsubo syndrome: a nationwide retrospective cohort study","volume":"12","author":"T Isogai","year":"2023","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"issue":"19","key":"pone.0336960.ref003","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1016\/j.jacc.2015.02.062","article-title":"Prevalence and Clinical Significance of Life-Threatening Arrhythmias in Takotsubo Cardiomyopathy","volume":"65","author":"T Stiermaier","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"pone.0336960.ref004","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.amjcard.2020.07.015","article-title":"Comparison of Complications and In-Hospital Mortality in Takotsubo (Apical Ballooning\/Stress) Cardiomyopathy Versus Acute Myocardial Infarction","volume":"132","author":"S Vallabhajosyula","year":"2020","journal-title":"Am J Cardiol"},{"issue":"10","key":"pone.0336960.ref005","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1056\/NEJMoa1406761","article-title":"Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy","volume":"373","author":"C Templin","year":"2015","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0336960.ref006","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jjcc.2022.12.011","article-title":"A study of takotsubo syndrome over 9\u00a0years at the Tokyo Cardiovascular Care Unit Network Registry","volume":"82","author":"K Arao","year":"2023","journal-title":"J Cardiol"},{"issue":"16","key":"pone.0336960.ref007","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.jacc.2018.07.072","article-title":"Stress Cardiomyopathy Diagnosis and Treatment: JACC State-of-the-Art Review","volume":"72","author":"H Medina deChazal","year":"2018","journal-title":"J Am Coll Cardiol"},{"issue":"12","key":"pone.0336960.ref008","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.117.006990","article-title":"Left Ventricular Thrombi in Takotsubo Syndrome: Incidence, Predictors, and Management: Results From the GEIST (German Italian Stress Cardiomyopathy) Registry","volume":"6","author":"F Santoro","year":"2017","journal-title":"J Am Heart Assoc"},{"issue":"22","key":"pone.0336960.ref009","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1093\/eurheartj\/ehy077","article-title":"International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management","volume":"39","author":"J-R Ghadri","year":"2018","journal-title":"Eur Heart J"},{"key":"pone.0336960.ref010","doi-asserted-by":"crossref","DOI":"10.1378\/chest.08-0782","article-title":"Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)","volume":"133","author":"J Hirsh","year":"2008","journal-title":"Chest"},{"issue":"1","key":"pone.0336960.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2188\/jea.JE20200288","article-title":"History and Profile of Diagnosis Procedure Combination (DPC): Development of a Real Data Collection System for Acute Inpatient Care in Japan","volume":"31","author":"K Hayashida","year":"2021","journal-title":"J Epidemiol"},{"issue":"1","key":"pone.0336960.ref012","doi-asserted-by":"crossref","first-page":"76","DOI":"10.37737\/ace.1.3_76","article-title":"Real world data in Japan: chapter II the diagnosis procedure combination Database","author":"H Yasunaga","year":"2019","journal-title":"Ann Clin Epidemiol"},{"issue":"7","key":"pone.0336960.ref013","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/pds.5636","article-title":"Validation studies of Japanese administrative health care data: A scoping review","volume":"32","author":"H Yamana","year":"2023","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"5","key":"pone.0336960.ref014","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1002\/ehf2.12843","article-title":"Role of climatic factors in the incidence of Takotsubo syndrome: A nationwide study from 2012 to 2016","volume":"7","author":"K Kanaoka","year":"2020","journal-title":"ESC Heart Fail"},{"key":"pone.0336960.ref015","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jclinepi.2018.03.004","article-title":"Association measures of claims-based algorithms for common chronic conditions were assessed using regularly collected data in Japan","volume":"99","author":"K Hara","year":"2018","journal-title":"J Clin Epidemiol"},{"issue":"3","key":"pone.0336960.ref016","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.ahj.2007.11.008","article-title":"Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction","volume":"155","author":"A Prasad","year":"2008","journal-title":"Am Heart J"},{"key":"pone.0336960.ref017","first-page":"61","article-title":"Functional Evaluation: The Barthel Index","volume":"14","author":"FI Mahoney","year":"1965","journal-title":"Md State Med J"},{"issue":"6","key":"pone.0336960.ref018","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/aje\/kwq433","article-title":"Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries","volume":"173","author":"H Quan","year":"2011","journal-title":"Am J Epidemiol"},{"issue":"5","key":"pone.0336960.ref019","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/pds.5423","article-title":"Validity of identification algorithms combining diagnostic codes with other measures for acute ischemic stroke in MID-NET\u00ae","volume":"31","author":"M Tanigawa","year":"2022","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"2","key":"pone.0336960.ref020","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jjcc.2016.10.015","article-title":"Usefulness of a healthcare database for epidemiological research in atrial fibrillation","volume":"70","author":"Y Koretsune","year":"2017","journal-title":"J Cardiol"},{"issue":"9","key":"pone.0336960.ref021","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1111\/jth.15799","article-title":"Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study","volume":"20","author":"T Fukasawa","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"1","key":"pone.0336960.ref022","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/bioinformatics\/btr597","article-title":"MissForest--non-parametric missing value imputation for mixed-type data","volume":"28","author":"DJ Stekhoven","year":"2012","journal-title":"Bioinformatics"},{"issue":"28","key":"pone.0336960.ref023","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1002\/sim.6607","article-title":"Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies","volume":"34","author":"PC Austin","year":"2015","journal-title":"Stat Med"},{"issue":"1","key":"pone.0336960.ref024","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1365-2753.2006.00610.x","article-title":"A comparison of multivariable regression models to analyse cost data","volume":"12","author":"S Dodd","year":"2006","journal-title":"J Eval Clin Pract"},{"issue":"15","key":"pone.0336960.ref025","doi-asserted-by":"crossref","DOI":"10.1161\/CIR.0000000000001092","article-title":"Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association","volume":"146","author":"GN Levine","year":"2022","journal-title":"Circulation"},{"issue":"7","key":"pone.0336960.ref026","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1093\/ehjcvp\/pvab057","article-title":"Apixaban vs. warfarin in patients with left ventricular thrombus: a prospective multicentre randomized clinical trial\u2021","volume":"8","author":"R Alcalai","year":"2022","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"issue":"5","key":"pone.0336960.ref027","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1002\/ehf2.14084","article-title":"Systematic review of efficacy of direct oral anticoagulants and vitamin K antagonists in left ventricular thrombus","volume":"9","author":"L Huang","year":"2022","journal-title":"ESC Heart Fail"},{"issue":"3","key":"pone.0336960.ref028","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1002\/ehf2.14713","article-title":"Effects of pharmacological interventions on mortality in patients with Takotsubo syndrome: a report from the SWEDEHEART registry","volume":"11","author":"P Petursson","year":"2024","journal-title":"ESC Heart Fail"},{"issue":"13","key":"pone.0336960.ref029","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1161\/CIRCULATIONAHA.121.055854","article-title":"Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications","volume":"145","author":"T Singh","year":"2022","journal-title":"Circulation"},{"issue":"1","key":"pone.0336960.ref030","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1161\/ATVBAHA.119.313491","article-title":"Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry","volume":"40","author":"KJ Ding","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"3","key":"pone.0336960.ref031","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3390\/ph17030371","article-title":"The Effect of Heparin and Other Exogenous Glycosaminoglycans (GAGs) in Reducing IL-1\u03b2-Induced Pro-Inflammatory Cytokine IL-8 and IL-6 mRNA Expression and the Potential Role for Reducing Inflammation","volume":"17","author":"M Jafri","year":"2024","journal-title":"Pharmaceuticals (Basel)"},{"issue":"13","key":"pone.0336960.ref032","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1161\/CIRCULATIONAHA.118.037975","article-title":"Myocardial and Systemic Inflammation in Acute Stress-Induced (Takotsubo) Cardiomyopathy","volume":"139","author":"C Scally","year":"2019","journal-title":"Circulation"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0336960","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:43:08Z","timestamp":1763059388000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0336960"}},"subtitle":[],"editor":[{"given":"Redoy","family":"Ranjan,","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0336960","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]}}}