{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:42:37Z","timestamp":1791164557004,"version":"4.1.0"},"reference-count":24,"publisher":"BMJ","issue":"19","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Heart"],"accepted":{"date-parts":[[2014,5,29]]},"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To quantify any risk of atrial fibrillation (AF) associated with ivabradine treatment by meta-analysis of clinical trial data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Medline, Embase, Web of Knowledge and the Cochrane central register of controlled trials were searched for double-blinded randomised controlled trials of ivabradine with a minimum follow-up period of 4\u2005weeks. For studies where AF data were unpublished, safety data were obtained from the European Medicines Agency (EMeA) website and personal communications. Studies were appraised for risk of bias using components recommended by the Cochrane Collaboration. Meta-analyses were performed of relative risk of AF and absolute risk difference of AF per year of treatment. The main outcome measure was incident AF during the follow-up period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>AF data were available from 11 studies: one from the published report, six from the EMeA and four from personal communications. Ivabradine treatment was associated with a relative risk of AF of 1.15 (95% CI 1.07 to 1.24, p=0.0027) among 21\u2005571 patients in the meta-analysis. From this we estimated that the number needed to harm for ivabradine would be 208 (95% CI 122 to 667) per year of treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>AF is a substantially more common side effect of ivabradine treatment than one patient in 10\u2005000, the risk presently reported in the product literature. The incidence of AF has not routinely been reported in clinical trials of ivabradine.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/heartjnl-2014-305482","type":"journal-article","created":{"date-parts":[[2014,6,21]],"date-time":"2014-06-21T03:37:38Z","timestamp":1403321858000},"page":"1506-1510","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":139,"title":["Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials"],"prefix":"10.1136","volume":"100","author":[{"given":"Ruairidh I R","family":"Martin","sequence":"first","affiliation":[{"name":"Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Department of Cardiology, Freeman Hospital, Newcastle, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Pogoryelova","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Santib\u00e1\u00f1ez","family":"Koref","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"Bourke","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Freeman Hospital, Newcastle, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Dawn","family":"Teare","sequence":"additional","affiliation":[{"name":"School of Health and Related Research, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard D","family":"Keavney","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2014,6,20]]},"reference":[{"key":"2025091923183602000_100.19.1506.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2006.03.006"},{"key":"2025091923183602000_100.19.1506.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61170-8"},{"key":"2025091923183602000_100.19.1506.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61198-1"},{"key":"2025091923183602000_100.19.1506.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2261"},{"key":"2025091923183602000_100.19.1506.5","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2610"},{"key":"2025091923183602000_100.19.1506.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809033391003"},{"key":"2025091923183602000_100.19.1506.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2011.02173.x"},{"key":"2025091923183602000_100.19.1506.8","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euq350"},{"key":"2025091923183602000_100.19.1506.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature11307"},{"key":"2025091923183602000_100.19.1506.10","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535"},{"key":"2025091923183602000_100.19.1506.11","doi-asserted-by":"crossref","unstructured":"Higgins JPT Green S ; Cochrane Collaboration. 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