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Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation &amp;gt;25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy &amp;gt;15\u2005mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3\/100 (99\/3316) patient-years] than in patients who never received SCB [SCBnever 4.9\/100 (150\/3083) patient-years, P &amp;lt; 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9\/100 (96\/3359) patient-years] than in SCBnever patients [4.2\/100 (135\/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537\/610 (88); SCBnever 472\/579 (82)].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF.<\/jats:p>\n                  <jats:p>Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euae121","type":"journal-article","created":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T07:31:52Z","timestamp":1714807912000},"source":"Crossref","is-referenced-by-count":45,"title":["Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3457-0936","authenticated-orcid":false,"given":"Andreas","family":"Rillig","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg\u2013Eppendorf , Martinistra\u00dfe 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research, Partner Site Hamburg\/Luebeck\/Kiel , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3735-8503","authenticated-orcid":false,"given":"Lars","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Atrial Fibrillation Network (AFNET) , Mendelstra\u00dfe 11, 48149 M\u00fcnster , Germany"},{"name":"Department of Cardiology II\u2014Electrophysiology, University Hospital M\u00fcnster , M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Borof","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg\u2013Eppendorf , Martinistra\u00dfe 52, 20246 Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2536-2871","authenticated-orcid":false,"given":"A John","family":"Camm","sequence":"additional","affiliation":[{"name":"Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George\u2019s University of London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1073-5337","authenticated-orcid":false,"given":"Harry J G M","family":"Crijns","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht , Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8223-7209","authenticated-orcid":false,"given":"Andreas","family":"Goette","sequence":"additional","affiliation":[{"name":"Atrial Fibrillation Network (AFNET) , Mendelstra\u00dfe 11, 48149 M\u00fcnster , Germany"},{"name":"St. Vincenz Hospital , Paderborn, Paderborn , Germany"},{"name":"Working Group of Molecular Electrophysiology, University Hospital Magdeburg , Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-8900","authenticated-orcid":false,"given":"G\u00fcnter","family":"Breithardt","sequence":"additional","affiliation":[{"name":"Atrial Fibrillation Network (AFNET) , Mendelstra\u00dfe 11, 48149 M\u00fcnster , Germany"},{"name":"Department of Cardiology II\u2014Electrophysiology, University Hospital M\u00fcnster , M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3799-7962","authenticated-orcid":false,"given":"Marc D","family":"Lemoine","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg\u2013Eppendorf , Martinistra\u00dfe 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research, Partner Site Hamburg\/Luebeck\/Kiel , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6818-6396","authenticated-orcid":false,"given":"Andreas","family":"Metzner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg\u2013Eppendorf , Martinistra\u00dfe 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research, Partner Site Hamburg\/Luebeck\/Kiel , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1389-8564","authenticated-orcid":false,"given":"Laura","family":"Rottner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg\u2013Eppendorf , Martinistra\u00dfe 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research, Partner Site Hamburg\/Luebeck\/Kiel , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1532-3315","authenticated-orcid":false,"given":"Ulrich","family":"Schotten","sequence":"additional","affiliation":[{"name":"Department of Physiology, Maastricht University , Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3737-6402","authenticated-orcid":false,"given":"Eik","family":"Vettorazzi","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg\u2013Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2974-3142","authenticated-orcid":false,"given":"Karl","family":"Wegscheider","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research, Partner Site Hamburg\/Luebeck\/Kiel , Germany"},{"name":"Atrial Fibrillation Network (AFNET) , Mendelstra\u00dfe 11, 48149 M\u00fcnster , Germany"},{"name":"Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg\u2013Eppendorf , Hamburg , 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Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"},{"name":"Institute of Cardiovascular Sciences, University of Birmingham , Birmingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-9509","authenticated-orcid":false,"given":"Renate B","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg\u2013Eppendorf , Martinistra\u00dfe 52, 20246 Hamburg , Germany"},{"name":"German Center for Cardiovascular Research, Partner Site Hamburg\/Luebeck\/Kiel , Germany"},{"name":"Atrial Fibrillation Network (AFNET) , Mendelstra\u00dfe 11, 48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5102-0955","authenticated-orcid":false,"given":"Christina","family":"Magnussen","sequence":"additional","affiliation":[{"name":"Department 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