{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:47:35Z","timestamp":1792442855154,"version":"4.5.0"},"reference-count":15,"publisher":"BMJ","issue":"8","funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Heart"],"accepted":{"date-parts":[[2016,9,27]]},"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We included patients who received \u22651 dose of study drug (n=18\u2005140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising\/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>NCT00412984; post-results.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/heartjnl-2016-309901","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T22:59:13Z","timestamp":1477349953000},"page":"623-628","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation"],"prefix":"10.1136","volume":"103","author":[{"given":"M Cecilia","family":"Bahit","sequence":"first","affiliation":[{"name":"INECO Neurociencias Oro\u00f1o, Rosario, Santa Fe, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato D","family":"Lopes","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M","family":"Wojdyla","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claes","family":"Held","sequence":"additional","affiliation":[{"name":"Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hanna","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos","family":"Vinereanu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy Carol Davila, Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine M","family":"Hylek","sequence":"additional","affiliation":[{"name":"Boston University Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freek","family":"Verheugt","sequence":"additional","affiliation":[{"name":"Heartcenter, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Goto","sequence":"additional","affiliation":[{"name":"Tokai University School of Medicine, Isehara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"Alexander","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Wallentin","sequence":"additional","affiliation":[{"name":"Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B","family":"Granger","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,10,24]]},"reference":[{"key":"2025091923442121000_103.8.623.1","doi-asserted-by":"crossref","first-page":"590","DOI":"10.7326\/0003-4819-147-8-200710160-00018","article-title":"Adjusted-dose warfarin versus aspirin for preventing stroke in patients with atrial fibrillation","volume":"147","author":"Hart","year":"2007","journal-title":"Ann Intern 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