{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T23:22:48Z","timestamp":1771456968163,"version":"3.50.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":1303,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Chang Gung Memorial Hospital, Taiwan","award":["CMRPG6H0482"],"award-info":[{"award-number":["CMRPG6H0482"]}]},{"name":"Chang Gung Memorial Hospital, Taiwan","award":["CMRPG6H0481"],"award-info":[{"award-number":["CMRPG6H0481"]}]},{"name":"Chang Gung Memorial Hospital, Taiwan","award":["CGRPG6J0041"],"award-info":[{"award-number":["CGRPG6J0041"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Ivabradine is indicated for heart failure (HF) patients with reduced ejection fraction (HFrEF), but limited data are available with regards to the use of ivabradine in those with a history of paroxysmal atrial fibrillation (AF). To assess the effect of ivabradine in HFrEF patients with paroxysmal AF, we analysed heart failure (HF) hospitalization and mortality from multiple-centre registry database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We conducted a multicentre observational matched cohort study, and this study enrolled patient with symptomatic HFrEF from 1 January 2015 to 31 December 2018 who had a history of paroxysmal AF in Chang Gung Memorial Hospital medical database in Taiwan. A total of 2042 patients were eligible for the study, of whom 887 were prescribed with ivabradine and 1115 were not. The primary outcome, including HF hospitalization and cardiovascular death, and individual outcome during the 12 month observation period were analysed after inverse probability of treatment weighting. The ivabradine group had significantly lower mean heart rate after 12 months follow-up than the non-ivabradine group (P &amp;lt; 0.05). The primary outcome was significantly higher in the ivabradine group than the non-ivabradine group after 12 months follow-up (hazard ratio [HR] = 1.58; 95% confidence interval [CI], 1.26\u20132.00, P &amp;lt; 0.001). Moreover, the ivabradine group had a significantly higher event rate of HF hospitalization (HR = 1.56; 95% CI, 1.40\u20131.75, P &amp;lt; 0.001) and HF death (HR = 1.67; 95% CI, 1.14\u20132.44, P = 0.009) than the non-ivabradine group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ivabradine treatment was associated with an increased risk of HF hospitalization in symptomatic HFrEF patients with a history of paroxysmal AF. Further prospective randomized studies are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13966","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T01:53:10Z","timestamp":1652406790000},"page":"2548-2557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ivabradine in Heart Failure Patients with Reduced Ejection Fraction and History of Paroxysmal Atrial Fibrillation"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9706-4534","authenticated-orcid":false,"given":"Yu-Sheng","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Cardiology, Chang Gung Memorial Hospital , Chiayi ,","place":["Taiwan"]},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University , Taoyuan ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeng-Yu","family":"Jan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chang Gung Memorial Hospital , Chiayi ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Jung","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Chang Gung Memorial Hospital , Chiayi ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Shyan","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Chang Gung Memorial Hospital , Chiayi ,","place":["Taiwan"]},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University , Taoyuan ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teng-Yao","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Chang Gung Memorial Hospital , Chiayi ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Chang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Chang Gung Memorial Hospital , Chiayi ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3184-4404","authenticated-orcid":false,"given":"Mien-Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine , Kaohsiung ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"2026012114141169900_ehf213966-bib-0001","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.phrs.2006.03.006","article-title":"Funny channels in the control of cardiac rhythm and mode of action of selective blockers","volume":"53","author":"DiFrancesco","year":"2006","journal-title":"Pharmacol Res"},{"key":"2026012114141169900_ehf213966-bib-0002","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0140-6736(10)61198-1","article-title":"Ivabradine and outcomes in chronic heart failure (SHIFT): A randomised placebo-controlled study","volume":"376","author":"Swedberg","year":"2010","journal-title":"Lancet"},{"key":"2026012114141169900_ehf213966-bib-0003","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)developed with the special contribution of the heart failure association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur Heart J"},{"key":"2026012114141169900_ehf213966-bib-0004","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.jacc.2020.11.022","article-title":"2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution set Oversight Committee","volume":"77","author":"Maddox","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2026012114141169900_ehf213966-bib-0005","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.yjmcc.2011.09.005","article-title":"Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart","volume":"51","author":"Herrmann","year":"2011","journal-title":"J Mol Cell Cardiol"},{"key":"2026012114141169900_ehf213966-bib-0006","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1177\/1753944716669658","article-title":"Emerging role of ivabradine for rate control in atrial fibrillation","volume":"10","author":"Turley","year":"2016","journal-title":"Ther Adv Cardiovasc Dis"},{"key":"2026012114141169900_ehf213966-bib-0007","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.118.009263","article-title":"Efficacy and safety of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with impaired liver function: a retrospective cohort study","volume":"7","author":"Wang","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"2026012114141169900_ehf213966-bib-0008","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/pds.4713","article-title":"The Chang Gung research database-a multi-institutional electronic medical records database for real-world epidemiological studies in Taiwan","volume":"28","author":"Shao","year":"2019","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2026012114141169900_ehf213966-bib-0009","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1093\/aje\/kwi307","article-title":"Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods","volume":"162","author":"Zhou","year":"2005","journal-title":"Am J Epidemiol"},{"key":"2026012114141169900_ehf213966-bib-0010","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.117.004112","article-title":"Ivabradine in heart failure: the representativeness of SHIFT (systolic heart failure treatment with the IF inhibitor ivabradine trial) in a broad population of patients with chronic heart failure","volume":"10","author":"Das","year":"2017","journal-title":"Circ Heart Fail"},{"key":"2026012114141169900_ehf213966-bib-0011","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1161\/CIRCULATIONAHA.117.033502","article-title":"2017 cardiovascular and stroke endpoint definitions for clinical trials","volume":"137","author":"Hicks","year":"2018","journal-title":"Circulation"},{"key":"2026012114141169900_ehf213966-bib-0012","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/00001648-200009000-00012","article-title":"Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men","volume":"11","author":"Hern\u00e1n","year":"2000","journal-title":"Epidemiology"},{"key":"2026012114141169900_ehf213966-bib-0013","volume-title":"Statistical analysis with missing data","author":"Little","year":"2019","edition":"3rd ed."},{"key":"2026012114141169900_ehf213966-bib-0014","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1136\/heartjnl-2014-305482","article-title":"Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials","volume":"100","author":"Martin","year":"2014","journal-title":"Heart"},{"key":"2026012114141169900_ehf213966-bib-0015","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.ijcard.2016.08.329","article-title":"Need for further studies on ivabradine in patients with persistent atrial fibrillation","volume":"223","author":"Kosiuk","year":"2016","journal-title":"Int J Cardiol"},{"key":"2026012114141169900_ehf213966-bib-0016","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijcard.2014.10.062","article-title":"Ivabradine for rate control in atrial fibrillation","volume":"179","author":"Kosiuk","year":"2015","journal-title":"Int J Cardiol"},{"key":"2026012114141169900_ehf213966-bib-0017","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ijcard.2015.08.207","article-title":"Addition of ivabradine to betablockers in patients with atrial fibrillation: effects on heart rate and exercise tolerance","volume":"202","author":"Caminiti","year":"2016","journal-title":"Int J Cardiol"},{"key":"2026012114141169900_ehf213966-bib-0018","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ijcard.2016.09.044","article-title":"Ivabradine reduced ventricular rate in patients with non-paroxysmal atrial fibrillation","volume":"224","author":"Wongcharoen","year":"2016","journal-title":"Int J Cardiol"},{"key":"2026012114141169900_ehf213966-bib-0019","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.cardfail.2018.09.016","article-title":"Heart failure differentially modulates the effects of ivabradine on the electrical activity of the sinoatrial node and pulmonary veins","volume":"24","author":"Chan","year":"2018","journal-title":"J Card Fail"},{"key":"2026012114141169900_ehf213966-bib-0020","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.jacep.2020.11.021","article-title":"Atrial fibrillation burden and clinical outcomes in heart failure: the CASTLE-AF trial","volume":"7","author":"Brachmann","year":"2021","journal-title":"JACC Clin Electrophysiol"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.13966","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.13966","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/9\/4\/2548\/65349212\/eschf_9_4_2548.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/9\/4\/2548\/65349212\/eschf_9_4_2548.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:16:45Z","timestamp":1769023005000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/9\/4\/2548\/8322915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":20,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,5,12]]},"published-print":{"date-parts":[[2022,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.13966","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,8]]},"published":{"date-parts":[[2022,5,12]]},"assertion":[{"value":"2021-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}