{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:54:57Z","timestamp":1755226497374,"version":"3.43.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG025152","R01DK102694","R01AG064589","R01DA048001","R01MH130435","R01AG060975"],"award-info":[{"award-number":["R01AG025152","R01DK102694","R01AG064589","R01DA048001","R01MH130435","R01AG060975"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>In a prior screening study, saxagliptin, a dipeptidyl peptidase\u20104 inhibitor (DPP\u20104i), was found to have an increased rate of serious bleeding when used concomitantly with several oral anticoagulants (OACs). We aimed to confirm or refute the associations between concomitant use of individual OACs and DPP\u20104is and serious bleeding in a large US database, using self\u2010controlled case series (SCCS) and case\u2010crossover (CCO) designs. The study population was eligible Medicare beneficiaries co\u2010exposed to a DPP\u20104i (precipitant) and either an OAC (object drug) or lisinopril (negative control object drug) in 2016\u20132020. For the SCCS, we used conditional Poisson regression to estimate adjusted rate ratios (RRs) between each co\u2010exposure (vs. not) and serious bleeding and divided the RR by the adjusted RR for the corresponding lisinopril + precipitant pair to obtain ratios of RRs (RRRs). For the CCO, we estimated the adjusted odds ratios (ORs) of exposure to the precipitant in the focal window vs. referent window using multivariable conditional logistic regression and divided the ORs in the object drug\u2010exposed cases over the ORs in negative object drug\u2010exposed cases to obtain the ratios of ORs (RORs). The adjusted RRRs for serious bleeding ranged from 0.32 (0.05\u20131.91) for apixaban\/lisinopril + saxagliptin to 3.49 (1.29\u20139.48) for warfarin\/lisinopril + linagliptin. The adjusted RORs ranged from 0.01 (0.00\u20130.20) for rivaroxaban\/lisinopril + saxagliptin to 2.99 (0.74\u201312.11) for apixaban\/lisinopril + linagliptin. While we could not confirm previously identified signals because of statistical imprecision, several numerically elevated estimates still warrant caution in concomitant use and further examination.<\/jats:p>","DOI":"10.1002\/cpt.3442","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T01:33:19Z","timestamp":1726104799000},"page":"1012-1016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concomitant Use of Oral Anticoagulants With Oral Dipeptidyl Peptidase\u20104 Inhibitors and Serious Bleeding Events"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-764X","authenticated-orcid":false,"given":"Thanh Phuong","family":"Pham Nguyen","sequence":"first","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Center for Clinical Epidemiology and Biostatistics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research, Department of Neurology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-9657","authenticated-orcid":false,"given":"Charles E.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Center for Clinical Epidemiology and Biostatistics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Leonard Davis Institute of Health Economics, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen M.","family":"Brensinger","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Center for Clinical Epidemiology and Biostatistics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-7525","authenticated-orcid":false,"given":"Warren B.","family":"Bilker","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Center for Clinical Epidemiology and Biostatistics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1520-2898","authenticated-orcid":false,"given":"Sophie P.","family":"Chung","sequence":"additional","affiliation":[{"name":"AthenaHealth, Inc.  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