{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:47:28Z","timestamp":1785422848657,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"crossref","award":["UIP-2020-02-8189"],"award-info":[{"award-number":["UIP-2020-02-8189"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"crossref"}]},{"award":["UIP-2020-02-8189"],"award-info":[{"award-number":["UIP-2020-02-8189"]}],"id":[{"id":"https:\/\/ror.org\/03n51vw80","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Aim: To evaluate associations between polymorphisms in CYP3A4 (*1B, *22), CYP3A5 (*3), CYP2J2 (*7, rs11572325), ABCB1 (c.1236C&gt;T, c.2677G&gt;T\/A, c.3435C&gt;T, rs4148738) and ABCG2 (c.421C&gt;A) and the occurrence of bleeding or occlusive events in patients receiving rivaroxaban in real-world clinical practice. Methods: A nested case-control study, divided into two substudies (bleeding and thromboembolic events), was conducted within a prospective cohort of 385 adults receiving rivaroxaban at University Hospital Centre Zagreb (September 2021\u2013September 2024). Bleeding events were classified per ISTH criteria, and genotyping was performed using TaqMan real-time PCR. Cases and controls were balanced using entropy balancing, and associations were estimated with Bayesian logistic regression under a skeptical prior N(0, 0.355); LASSO regression was used to identify clinical and genetic predictors of outcomes. Results: In total, 71 patients (18.4%) experienced bleeding events, most frequently gastrointestinal (47.9%), while 314 patients served as controls. No pharmacogenomic variant showed a clear association with bleeding risk (raw and balanced odds ratios 0.80\u20131.35; 95% credible intervals crossing 1.0). LASSO regression identified age (OR 2.00 per decade), gastrointestinal comorbidity (OR 8.77), and eGFR as the dominant predictors of bleeding. Twenty-one patients experienced occlusive events (15 venous, 6 arterial); however, the low event count precluded meaningful pharmacogenomic analysis. Conclusions: Individual pharmacogenomic variants in CYP3A4, CYP3A5, CYP2J2, ABCB1, and ABCG2 together with pharmacogenetic-based phenotypes were not associated with clinically relevant bleeding in rivaroxaban-treated patients. Traditional clinical risk factors, particularly advanced age and gastrointestinal comorbidity, remain the dominant determinants of adverse outcomes. Routine pharmacogenomic testing to guide rivaroxaban dosing is not currently supported.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070884","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:00:17Z","timestamp":1784548817000},"page":"884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenomics of Rivaroxaban: Association of CYP3A4, CYP3A5, CYP2J2, ABCB1, and ABCG2 Variants with Bleeding and Thrombotic Outcomes in Real-World Clinical Practice"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6622-7572","authenticated-orcid":false,"given":"Ana Marija","family":"Sli\u0161kovi\u0107","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Diseases, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-1194","authenticated-orcid":false,"given":"Vladimir","family":"Trkulja","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Pharmacology, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana","family":"Ganoci","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Pharmacology, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"},{"name":"Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5883-7979","authenticated-orcid":false,"given":"Tamara","family":"Bo\u017eina","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Biochemistry and Clinical Chemistry, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6587-2315","authenticated-orcid":false,"given":"Vedran","family":"Pa\u0161ara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1340-1917","authenticated-orcid":false,"given":"Majda","family":"Vrki\u0107 Kirhmajer","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Internal Medicine, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozefina","family":"Pali\u0107","sequence":"additional","affiliation":[{"name":"Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3977-9712","authenticated-orcid":false,"given":"Dominik","family":"Striki\u0107","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9617-080X","authenticated-orcid":false,"given":"Marino","family":"Naran\u010di\u0107","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0888-5005","authenticated-orcid":false,"given":"Ivana","family":"Sopek Merka\u0161","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Special Hospital for Medical Rehabilitation Krapinske Toplice, 49217 Krapinske Toplice, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2824-9222","authenticated-orcid":false,"given":"Iveta","family":"Mer\u0107ep","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"},{"name":"Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1482-6503","authenticated-orcid":false,"given":"Jo\u0161ko","family":"Bulum","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Internal Medicine, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-1920","authenticated-orcid":false,"given":"Livija","family":"\u0160imi\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Medical Chemistry, Biochemistry and Clinical Chemistry, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Heestermans, M., Poenou, G., Hamzeh-Cognasse, H., Cognasse, F., and Bertoletti, L. 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