{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T01:56:38Z","timestamp":1774230998287,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In this post hoc analysis, we assessed patient characteristics as predictors of dronedarone trough concentrations and characterized the relationship of trough concentrations of dronedarone with its efficacy and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis<\/jats:title><jats:p>Dronedarone is recommended as a 400\u2009mg twice daily dose taken orally with meals. We hypothesize that drug concentration\/bioavailability of dronedarone, measured as above\u2010 and below\u2010median trough concentrations, does not impact the efficacy outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Average trough concentrations (C<jats:sub>trough_avg<\/jats:sub>) across multiple timepoints were calculated for each patient, and patient C<jats:sub>trough_avg<\/jats:sub> values were categorized as below\u2010median or above\u2010median concentrations. The effect of patient baseline characteristics on dronedarone C<jats:sub>trough_avg<\/jats:sub> was assessed in the below\u2010median versus above\u2010median groups. The effect of dronedarone in each C<jats:sub>trough_avg<\/jats:sub> group versus placebo on risk of first atrial fibrillation\/atrial flutter (AF\/AFL) recurrence and safety was also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 1795 plasma samples were available from 507 dronedarone\u2010treated patients. An above\u2010median C<jats:sub>trough_avg<\/jats:sub> was associated with age \u226575 years, female sex, lower weight, higher pacemaker use, and higher oral anticoagulant use. The risk of adjudicated first AF\/AFL recurrence was significantly lower with dronedarone versus placebo in the below\u2010median (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.56\u20130.91; <jats:italic>p<\/jats:italic>\u2009=\u2009.0054) and above\u2010median groups (HR: 0.63; 95% CI: 0.50\u20130.81; <jats:italic>p<\/jats:italic>\u2009=\u2009.0002). No difference in risk of AF\/AFL recurrence was observed between the above\u2010 and below\u2010median groups. Safety and tolerability of dronedarone were similar between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Significant reduction in AF\/AFL recurrence was observed in patients treated with dronedarone versus placebo, regardless of dronedarone concentrations above or below the median value.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.23768","type":"journal-article","created":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T13:04:35Z","timestamp":1642251875000},"page":"119-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Predictors of dronedarone plasma drug concentrations and effect on atrial fibrillation\/atrial flutter recurrence: Analyses from the EURIDIS and ADONIS studies"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9852-2867","authenticated-orcid":false,"given":"Munveer","family":"Thind","sequence":"first","affiliation":[{"name":"Division of Cardiology Lankenau Heart Institute  Wynnewood Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"McKindley","sequence":"additional","affiliation":[{"name":"Sanofi  Bridgewater New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-1866","authenticated-orcid":false,"given":"James A.","family":"Reiffel","sequence":"additional","affiliation":[{"name":"Division of Cardiology Columbia University  New York City New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-4554","authenticated-orcid":false,"given":"Gerald V.","family":"Naccarelli","sequence":"additional","affiliation":[{"name":"Division of Cardiology Penn State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Stewart","sequence":"additional","affiliation":[{"name":"Sanofi  Laval Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-1638","authenticated-orcid":false,"given":"Peter R.","family":"Kowey","sequence":"additional","affiliation":[{"name":"Division of Cardiology Lankenau Heart Institute  Wynnewood Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.03.022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000491"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62343-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz782"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2019422"},{"key":"e_1_2_9_7_1","first-page":"373","article-title":"ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio\u2010Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"2021","author":"Hindricks G","year":"2020","journal-title":"Eur Heart J"},{"key":"e_1_2_9_8_1","unstructured":"MULTAQ\u00ae (dronedarone) prescribing information. Sanofi\u2010Aventis US Bridgewater NJ; 2017."},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054686"},{"key":"e_1_2_9_10_1","unstructured":"European Medicines Agency. 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