{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:02:37Z","timestamp":1784512957771,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Limited evidence suggests donepezil might pose an increased risk of malignant arrhythmias. We examined whether donepezil initiation was associated with a higher risk of hospitalization for malignant arrhythmia compared to other acetylcholinesterase inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Population\u2010based cohort study using linked administrative databases from seven Canadian provinces (BC, AB, SK, MB, ON, PEI, NL). We included individuals aged \u2265\u200966 who were new users of donepezil, galantamine, or rivastigmine from April 1st, 2011, to January 31st, 2019. We used multivariable Cox proportional hazards regression to estimate the risk of hospitalization for malignant arrhythmia among new donepezil users compared to new users of galantamine or rivastigmine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 162\u2009616 subjects (mean age 82, 40% male). Most (127\u2009103; 78%) were treated with donepezil, while 25\u2009597 (15.7%) received galantamine, (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096541; 4.0%) received oral rivastigmine, and (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093375; 2.1%) received transdermal rivastigmine. The median age was 82\u2009years, and 59.8% were women. Baseline characteristics were generally well balanced. During a median follow\u2010up of 386\u2009days (maximum 2616\u2009days), we identified 90 hospitalizations for malignant arrhythmias, including 58 in the donepezil group (23 per 100\u2009000 person\u2010years) and 32 for other AChEIs (44 per 100\u2009000 person\u2010years). Cumulative incidence curves showed a lower risk among donepezil initiators (Log\u2010Rank\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0026; Wilcoxon\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0008). Crude regression suggested a reduced hazard (HR 0.52; 95% CI 0.34\u20130.80), which persisted after adjustment (aHR 0.55; 95% CI 0.36\u20130.85). In drug\u2010specific analyses, donepezil initiators had a lower hazard relative to galantamine (aHR 0.49; 95% CI 0.31\u20130.77) but not rivastigmine (aHR 0.90; 95% CI 0.36\u20132.27). Sensitivity analyses\u2014including alternative diagnosis field definitions, restricted follow\u2010up, modified exclusion criteria, and propensity score adjustment\u2014yielded consistent findings. No clear dose\u2013response pattern was observed for any AChEI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this population\u2010based cohort study, initiation of donepezil was not associated with an increased risk of malignant arrhythmias compared to initiation of galantamine or rivastigmine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70426","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T01:54:56Z","timestamp":1783994096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hospitalization for Malignant Arrhythmias Following Initiation of Donepezil: A Retrospective Cohort Study"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2224-6282","authenticated-orcid":false,"given":"Yichang","family":"Huang","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Waterloo  Kitchener Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-8721","authenticated-orcid":false,"given":"John\u2010Michael","family":"Gamble","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo  Kitchener Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0368-4212","authenticated-orcid":false,"given":"David N.","family":"Juurlink","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre  Toronto Ontario Canada"},{"name":"Department of Medicine and Pediatrics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-9528","authenticated-orcid":false,"given":"Mhd. Wasem","family":"Alsabbagh","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo  Kitchener Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Alzheimer's Assocation \u201cFacts and Figures.\u201d"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144337"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12578"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010017\u20100519\u20100"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.622"},{"key":"e_1_2_10_7_1","unstructured":"D.Juurlink C.Preyra R.Croxford et\u00a0al. \u201cCanadian Institute for Health Information Discharge Abstract Database: A Validation Study. 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