{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:48:47Z","timestamp":1793317727245,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Rivaroxaban is frequently used for stroke prevention in atrial fibrillation. Clinicians increasingly encounter complex decision\u2010making regarding oral anticoagulant prescription in older patients with atrial fibrillation. Genetic contributors to variability in rivaroxaban exposure and clinical outcomes remain uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">A total of 168 eligible participants were consecutively recruited in this prospective observational study. Rivaroxaban dose regimens were accounted for using dose\u2010specific standardization, dose\u2010stratified analyses, and a sensitivity analysis excluding the small 5\u2010mg and 20\u2010mg dose groups. Associations of targeted genetic variants with rivaroxaban concentration, anti\u2010FXa (factor Xa) activity, and overall bleeding were evaluated. Exploratory protein\u2010structure modeling was performed to generate preliminary mechanistic hypotheses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Median age was 76\u2009years (interquartile range, 71\u201381), and 10 mg was the most frequently prescribed dose. Aldo\u2010keto reductase family 7 member A3 rs1738023 and rs1738025 were nominally associated with trough concentration (both\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.020). Trough anti\u2010FXa activity was nominally associated with ATP\u2010binding cassette subfamily G member 2 rs2622604 (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.042) and ATP\u2010binding cassette transporter B1 rs1128503 (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.0074). Overall bleeding occurred in 23 patients (13.7%). In Firth logistic regression adjusted for age and prior bleeding, ATP\u2010binding cassette transporter B1 rs1045642 AG genotype was nominally associated with higher bleeding odds than AA (adjusted odds ratio [aOR], 4.65 [95% CI, 1.02\u201344.61];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.047), whereas ATP\u2010binding cassette transporter B1 rs4148738 TT was nominally associated with lower odds than CC\/CT (aOR, 0.34 [95% CI, 0.10\u20130.96];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.042). No association met the Bonferroni\u2010corrected significance threshold.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Selected ATP\u2010binding cassette transporter B1, ATP\u2010binding cassette subfamily G member 2, and aldo\u2010keto reductase family 7 member A3 variants showed exploratory associations with rivaroxaban pharmacokinetics, pharmacodynamics, and overall bleeding. As none of these associations remained statistically significant after correction for multiple testing, the findings require validation in larger, ethnically diverse cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.126.049831","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T10:25:20Z","timestamp":1784975120000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Genetic Variants With Rivaroxaban Pharmacokinetics and Pharmacodynamics in Older Patients With Atrial Fibrillation: A Prospective Cohort Study"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-5199","authenticated-orcid":false,"given":"Guoquan","family":"Chen","sequence":"first","affiliation":[{"name":"Medical College of Zhejiang University","place":["Jinhua, 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University","place":["Jinhua, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9801-0509","authenticated-orcid":false,"given":"Ganbo","family":"Que","sequence":"additional","affiliation":[{"name":"Longyan Second Hospital","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Longyan Second Hospital","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6789-1620","authenticated-orcid":false,"given":"Shuqiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Longyan Second Hospital","place":["Longyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9107-8027","authenticated-orcid":false,"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Zhejiang University School of 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