{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:02:39Z","timestamp":1788134559197,"version":"build-2803163510"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels\/receptors and usually altered atrial structure. AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels\/receptors. Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs. We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance\/safety.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone\u2019s negative inotropic effect\u2014see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed. Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations. Neither placebo nor either drugs alone significantly reduced AFB. Conversely, ranolazine 750 mg BID\/dronedarone 225 mg BID reduced AFB by 59% versus placebo (\n              <jats:italic>P<\/jats:italic>\n              =0.008), whereas ranolazine 750 mg BID\/dronedarone 150 mg BID reduced AFB by 43% (\n              <jats:italic>P<\/jats:italic>\n              =0.072). Both combinations were well tolerated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance\/safety, in the population enrolled.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT01522651.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.115.002856","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T01:54:59Z","timestamp":1438307699000},"page":"1048-1056","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":153,"title":["The HARMONY Trial"],"prefix":"10.1161","volume":"8","author":[{"given":"James A.","family":"Reiffel","sequence":"first","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. John","family":"Camm","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz","family":"Belardinelli","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewan","family":"Zeng","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Karwatowska-Prokopczuk","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Olmsted","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Zareba","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Rosero","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kowey","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology, Department of Medicine, Columbia University, New York, NY (J.A.R.); Department of Cardiovascular Sciences, St Georges University of London, London, United Kingdom (A.J.C.); Cardiovascular Clinical Research, Gilead Sciences, Inc, Foster City, CA (L.B., D.Z., E.K.-P., A.O.); Division of Cardiology, Department of Medicine, University of Rochester Medical Center, NY (W.Z., S.R.); Lankenau Institute for Medical Research, Wynnewood, PA (P.K.); and Division of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.595140"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.18.2370"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000441139.02102.80"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000040"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq278"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2012.12.019"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.03.034"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2009.11.046"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eut232"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2009"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302226"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.02.555"},{"key":"e_1_3_3_14_2","first-page":"409","volume-title":"In: Advances in Antiarrhythmic Drug Therapy. Cardiac Electrophysiology Clinics","author":"Morrow JP","year":"2010","unstructured":"Morrow JP, Reiffel JA. Chronic maintenance of sinus rhythm in patients with atrial fibrillation using antiarrhythmic drugs: update 2010. , Kowey PR, Naccarelli GV, eds. In: Advances in Antiarrhythmic Drug Therapy. Cardiac Electrophysiology Clinics. Philadelphia, PA: WB Saunders and co; 2010:409\u2013418."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.06.004"},{"key":"e_1_3_3_16_2","first-page":"1","volume-title":"In: Cardiac Electrophysiology","author":"Reiffel JA","year":"2011","unstructured":"Reiffel JA. Case 163. , Natale A, Al-Ahmad A, Wang PJ, eds. In: Cardiac Electrophysiology. London: Springer; 2011:1\u20134."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.03.021"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.65.766.519"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.02.016"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.2174\/1573403X10666140513110247"},{"key":"e_1_3_3_21_2","first-page":"157","article-title":"Dronedarone: where does it fit in the AF therapeutic armamentarium?","volume":"5","author":"Reiffel JA","year":"2013","unstructured":"Reiffel JA. Dronedarone: where does it fit in the AF therapeutic armamentarium? JAFIB. 2013;5:157\u2013163.","journal-title":"JAFIB"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054686"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0803778"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0800456"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109867"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.2459\/JCM.0b013e328365b554"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2008.03.018"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.4022\/jafib.v2i1.572"},{"key":"e_1_3_3_29_2","first-page":"S258","article-title":"Ranolazine versus amiodarone for prophylaxis against atrial fibrillation following coronary artery bypass surgery. [Abstract P04-03]","volume":"7","author":"Miles RH","year":"2010","unstructured":"Miles RH, Murdock DK. Ranolazine versus amiodarone for prophylaxis against atrial fibrillation following coronary artery bypass surgery. [Abstract P04-03] Heart Rhythm. 2010;7:S258\u2013259.","journal-title":"Heart Rhythm"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8159.2010.02967.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8159.1998.tb00132.x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8159.1998.tb00160.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026240625182"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(02)03375-1"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.02.018"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/sun028"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01357.2007"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00444.2009"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2009.01437.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001129"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eus399"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2011.03.045"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs163"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.01.021"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200302000-00007"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.08.600"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2012.09.015"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/1755-5922.12035"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(03)00321-X"}],"container-title":["Circulation: Arrhythmia and Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCEP.115.002856","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:35:35Z","timestamp":1715556935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCEP.115.002856"}},"subtitle":["Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism"],"short-title":[],"issued":{"date-parts":[[2015,10]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1161\/CIRCEP.115.002856"],"URL":"https:\/\/doi.org\/10.1161\/circep.115.002856","relation":{},"ISSN":["1941-3149","1941-3084"],"issn-type":[{"value":"1941-3149","type":"print"},{"value":"1941-3084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10]]},"assertion":[{"value":"2015-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}