{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:13:49Z","timestamp":1791980029728,"version":"4.4.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,3,18]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Bleeding after starting anticoagulation for atrial fibrillation (AF) may be the first sign of malignancy, especially in elderly individuals. There are no recommendations to guide investigations for malignancy after new-onset bleeding after anticoagulation for AF. Our objective was to determine the association of bleeding after starting oral anticoagulation for AF with new diagnoses of malignancy in a population-wide sample.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We conducted a population-based cohort study using linked administrative data sets of people \u226566 years of age who newly initiated warfarin or direct oral anticoagulants after diagnosis with AF between 2008 and 2022. Follow-up was 2 years after starting anticoagulation. We excluded patients with valvular disease, chronic dialysis, venous thromboembolism, previous cancer, or previously documented bleeding. Bleeding was identified from hospital\/emergency department discharge records and physician billings, then handled as a time-varying covariate in cause-specific regression models while adjusting for baseline characteristics. The primary outcome was incident malignancy. We also determined the site of origin of the malignancy and the stage at diagnosis if indicated in the Ontario Cancer Registry. Analyses were repeated while limiting the exposure to specific bleeding sites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Among 119\u2009480 people (mean age, 77.4 years; 52% men) who started anticoagulants, 26\u2009037 (21.8%) had documented bleeding, and 5800 (4.9%) were diagnosed with malignancy within the next 2 years. Bleeding was associated with a higher hazard of cancer diagnosis with a hazard ratio (HR) of 4.0 (95% CI, 3.8\u20134.3). The HRs for any malignancy were 5.0 (95% CI, 4.6\u20135.5) for gastrointestinal, 5.0 (95% CI, 4.4\u20135.7) for genitourinary, 4.0 (95% CI, 3.5\u20134.6) for respiratory, 1.8 (95% CI, 1.4\u20132.2) for intracranial, and 1.5 (95% CI, 1.2\u20132.0) for nasopharyngeal bleeds. The HRs were substantially higher for cancers concordant with the bleeding site (gastrointestinal, 15.4; genitourinary, 11.8; respiratory, 10.1). Cancers were diagnosed at an earlier stage after bleeding (27.6% stage 4 after bleeding versus 31.3% without bleeding;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.029).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In anticoagulated patients with AF, bleeding was strongly associated with new cancer diagnoses. Antecedent bleeding was associated with cancer diagnosis at an earlier stage. This highlights the importance of timely investigations in patients with bleeding after anticoagulation for AF, rather than attributing bleeding as an expected adverse effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.124.070865","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T05:01:45Z","timestamp":1740027705000},"page":"773-782","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Bleeding and New Malignancy Diagnoses After Anticoagulation for Atrial Fibrillation: A Population-Based Cohort Study"],"prefix":"10.1161","volume":"151","author":[{"given":"Kavi","family":"Grewal","sequence":"first","affiliation":[{"name":"Temerty Faculty of Medicine (K.G.), University of Toronto, Canada."},{"name":"Department of Medicine, Women\u2019s College Hospital, Toronto, Canada (K.G., H.A.-Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Wang","sequence":"additional","affiliation":[{"name":"ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Canada (X.W., P.C.A., C.A.J., I.N.-A., D.T.K., D.S.L., H.A.-Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3337-233X","authenticated-orcid":true,"given":"Peter C.","family":"Austin","sequence":"additional","affiliation":[{"name":"Institute of Health Policy, Management, and Evaluation (P.C.A., C.A.J., I.N.-A., D.S.L., H.A.-Q.), University of Toronto, Canada."},{"name":"ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Canada (X.W., P.C.A., C.A.J., I.N.-A., D.T.K., D.S.L., H.A.-Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5274-7251","authenticated-orcid":true,"given":"Cynthia A.","family":"Jackevicius","sequence":"additional","affiliation":[{"name":"Institute of Health Policy, Management, and Evaluation (P.C.A., C.A.J., I.N.-A., D.S.L., H.A.-Q.), University of Toronto, Canada."},{"name":"ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Canada (X.W., P.C.A., C.A.J., I.N.-A., D.T.K., D.S.L., H.A.-Q.)."},{"name":"Department of Pharmacy, Veterans Affairs Greater Los Angeles Healthcare System, CA (C.A.J.)."},{"name":"Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA (C.A.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbar","family":"Nardi-Agmon","sequence":"additional","affiliation":[{"name":"Institute of Health Policy, Management, and Evaluation (P.C.A., C.A.J., I.N.-A., D.S.L., H.A.-Q.), University of Toronto, Canada."},{"name":"ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Canada (X.W., P.C.A., C.A.J., I.N.-A., D.T.K., D.S.L., H.A.-Q.)."},{"name":"Peter Munk Cardiac Centre, Department of Medicine, Division of Cardiology, University Health Network, Toronto, Canada (I.N.-A., D.S.L., P.T., H.A.-Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-8051","authenticated-orcid":true,"given":"Dennis T.","family":"Ko","sequence":"additional","affiliation":[{"name":"ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Canada (X.W., P.C.A., C.A.J., I.N.-A., D.T.K., D.S.L., H.A.-Q.)."},{"name":"Department of Medicine, Schulich Heart Centre, Sunnybrook Hospital, Toronto, Canada (D.T.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-745X","authenticated-orcid":true,"given":"Douglas S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Health Policy, Management, and Evaluation (P.C.A., C.A.J., I.N.-A., D.S.L., H.A.-Q.), University of Toronto, Canada."},{"name":"ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Canada (X.W., P.C.A., C.A.J., I.N.-A., D.T.K., D.S.L., H.A.-Q.)."},{"name":"Peter Munk Cardiac Centre, Department of Medicine, Division of Cardiology, University Health Network, Toronto, Canada (I.N.-A., D.S.L., P.T., H.A.-Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6497-1098","authenticated-orcid":true,"given":"Paaladinesh","family":"Thavendiranathan","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre, Department of Medicine, Division of Cardiology, University Health Network, Toronto, Canada (I.N.-A., D.S.L., P.T., H.A.-Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8352-8975","authenticated-orcid":true,"given":"Michael","family":"Fradley","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine at the University of Pennsylvania, Philadelphia (M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-3520","authenticated-orcid":true,"given":"Paul","family":"Dorian","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Unity Health, Toronto, Canada (P.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7105-7931","authenticated-orcid":true,"given":"Husam","family":"Abdel-Qadir","sequence":"additional","affiliation":[{"name":"Institute of Health Policy, Management, and Evaluation (P.C.A., C.A.J., I.N.-A., D.S.L., H.A.-Q.), University of Toronto, Canada."},{"name":"Department of Medicine, Women\u2019s College Hospital, Toronto, Canada (K.G., H.A.-Q.)."},{"name":"ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, Canada (X.W., P.C.A., C.A.J., I.N.-A., D.T.K., D.S.L., H.A.-Q.)."},{"name":"Peter Munk Cardiac Centre, Department of Medicine, Division of Cardiology, University Health Network, Toronto, Canada (I.N.-A., D.S.L., P.T., H.A.-Q.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001193"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.016836"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.11838"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-6314-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190324"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.01.540"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euv317"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-05-0424"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hs0102.101817"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12875-016-0574-0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(88)90052-2"},{"key":"e_1_3_3_13_2","unstructured":"Flora M Trevor VI. 2016 Ontario marginalization index user guide. Toronto: St. Michael\u2019s Hospital; 2018. Joint publication with Public Health Ontario. Accessed December 16 2021. https:\/\/www.publichealthontario.ca\/-\/media\/documents\/o\/2017\/on-marg-userguide.pdf"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.23889\/ijpds.v4i2.1135"},{"key":"e_1_3_3_15_2","unstructured":"Personal Health Information Protection Act 2004 S.O. 2004 c. 3 Sched. A. Government of Ontario. Accessed January 29 2025. https:\/\/www.ontario.ca\/laws\/statute\/04p03"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2020.09.001"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2016.06.006"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.121218"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000080290.39027.48"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0828-282x(10)70412-8"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12913-018-3148-0"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.058949"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.24095\/hpcdp.33.3.06"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.25011\/cim.v39i2.26483"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.25011\/cim.v44i2.36354"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2013.07.676"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0201120"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30668-8"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.4970"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.118.004580"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","unstructured":"van Buuren S. Flexible Imputation of Missing Data. Second Edition. Accessed February 18 2025. https:\/\/stefvanbuuren.name\/fimd\/: Chapman & Hall\/CRC; 2018.","DOI":"10.1201\/9780429492259"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/03610910902859574"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041949"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.026588"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-12-200706190-00007"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.124.070865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T20:42:58Z","timestamp":1774903378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.124.070865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":34,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,3,18]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.124.070865"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.124.070865","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]},"assertion":[{"value":"2024-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}