{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:59:59Z","timestamp":1785178799876,"version":"3.55.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Population Health and Outcomes"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Direct oral anticoagulants such as apixaban and rivaroxaban, have transformed the management of thromboembolic disorders. Randomized controlled trials were initiated in 2017 (COBRRA-VTE [Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism]) and 2021 (COBRRA-AF [Comparison of Bleeding Risk Between Rivaroxaban and Apixaban in Patients With Atrial Fibrillation]) to directly compare apixaban and rivaroxaban on the risk of bleeding in patients with venous thromboembolism (VTE) and atrial fibrillation (AF). We aimed to emulate the design and measurements of these ongoing trials and use US health care insurance claims data to predict their findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      In cohort studies designed to emulate COBRRA-VTE (REGISTRATION: URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT05264168) and COBRRA-AF (NCT05256797) in 3 US health care insurance claims databases (Medicare, Optum Clinformatics, Merative MarketScan), the risk of bleeding with apixaban was evaluated relative to the risk with rivaroxaban. Pretreatment confounding factors were adjusted for via 1:1 propensity score matching. The primary outcome was a composite of major bleeding and clinically relevant non-major bleeding (defined using\n                      <jats:italic toggle=\"yes\">International Classification of Diseases, Ninth Revision<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Tenth Revision<\/jats:italic>\n                      diagnosis codes) recorded in the inpatient setting. Results across databases were pooled using fixed-effects meta-analyses. Protocols were preregistered on\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      before inferential analyses were conducted.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>In the COBRRA-VTE emulation (N=14\u2009023 matched pairs, mean age=67 years, 55% women), we observed a 31% decreased risk of bleeding for apixaban compared with rivaroxaban (incidence rate per 100 person-years: apixaban, 12.8; rivaroxaban, 19.1; hazard ratio, 0.69 [95% CI, 0.59\u20130.79]). For the COBRRA-AF emulation (N=176\u2009990 matched pairs, mean age=74 years, 50% women), we similarly observed a 31% decreased risk for apixaban compared with rivaroxaban (incidence rate per 100 person-years: apixaban, 6.4; rivaroxaban, 9.2; hazard ratio, 0.69 [95% CI, 0.66\u20130.71]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In database studies that closely emulated the design and measurements of the COBRRA-VTE and COBRRA-AF trials, a substantially lower risk of bleeding with apixaban was observed, consistent with the results of COBRRA-VTE (published after completion of our analyses), and indirect comparisons from other trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circoutcomes.125.012892","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:00:25Z","timestamp":1782982825000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Bleeding Risk With Apixaban Versus Rivaroxaban: A Reference Trial Emulation Predicting the Results of COBRRA-VTE and COBRRA-AF Using US Health Care Claims"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6684-2337","authenticated-orcid":true,"given":"Mufaddal","family":"Mahesri","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.M., S.S., K.J.L., L.Z., 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Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.M., S.S., K.J.L., L.Z., S.V.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2846-0503","authenticated-orcid":true,"given":"John","family":"Concato","sequence":"additional","affiliation":[{"name":"Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD (J.C., M.C.B.)."},{"name":"Department of Medicine, Yale University School of Medicine, New Haven, CT (J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-4414","authenticated-orcid":true,"given":"Marie C.","family":"Bradley","sequence":"additional","affiliation":[{"name":"Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD (J.C., 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