{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:51:30Z","timestamp":1792007490932,"version":"4.4.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Direct oral anticoagulants (DOACs) exhibit considerable individual variability in effectiveness and bleeding risk, possibly due to genetic differences. This study assessed how genetic polymorphisms impact the pharmacokinetics (PK) and outcomes of DOACs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for pharmacogenomic studies related to DOACs up to October 29, 2025. Meta-analyses were performed using RevMan 5.4 for evaluated results with \u22653 studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-nine studies involving 13,300 patients were included, with 19 studies eligible for meta-analysis. For dabigatran, carriers of the\n                      <jats:italic>CES1<\/jats:italic>\n                      rs2244613 C allele was associated with both lower trough concentration (C\n                      <jats:sub>trough<\/jats:sub>\n                      ) and reduced bleeding risk compared with AA homozygotes.\n                      <jats:italic>CES1<\/jats:italic>\n                      rs8192935 and\n                      <jats:italic>ABCB1<\/jats:italic>\n                      rs4148738 were also associated with dabigatran exposure. For rivaroxaban, the\n                      <jats:italic>ABCB1<\/jats:italic>\n                      rs1045642 TT genotype was consistently associated with lower dose-adjusted C\n                      <jats:sub>trough<\/jats:sub>\n                      across four subgroups. Polymorphisms in\n                      <jats:italic>ABCB1<\/jats:italic>\n                      rs1045642 were linked to altered bleeding risk, whereas\n                      <jats:italic>ABCB1<\/jats:italic>\n                      (rs1128503, rs4148738, rs2032582),\n                      <jats:italic>ABCG2<\/jats:italic>\n                      rs2231142,\n                      <jats:italic>CYP3A5<\/jats:italic>\n                      rs776746, and\n                      <jats:italic>CYP2J2<\/jats:italic>\n                      rs890293 showed no statistically significant association with bleeding events. For apixaban,\n                      <jats:italic>ABCG2<\/jats:italic>\n                      rs2231142 may influence PK profiles, while\n                      <jats:italic>ABCB1<\/jats:italic>\n                      rs1045642 was associated with a reduced risk of bleeding. In the case of edoxaban, polymorphisms in\n                      <jats:italic>SLCO1B1<\/jats:italic>\n                      may affect metabolite exposure and contribute to variability in bleeding risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Genetic polymorphisms in\n                      <jats:italic>CES1<\/jats:italic>\n                      ,\n                      <jats:italic>ABCB1<\/jats:italic>\n                      , and\n                      <jats:italic>SLCO1B1<\/jats:italic>\n                      are associated with variability in the PK and bleeding risk of DOACs. However, due to the observational nature, heterogeneity, and limited sample sizes of included studies, current evidence is insufficient to support genotype-guided dosing in clinical practice. Large prospective studies are needed to validate these findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>PROSPERO CRD420251240030.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1792186","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:21:51Z","timestamp":1776140511000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacogenomics of direct oral anticoagulants: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Huaru","family":"Chai","sequence":"first","affiliation":[{"name":"Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences &Peking Union Medical College","place":["Beijing, China"]},{"name":"Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Huo","sequence":"additional","affiliation":[{"name":"Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences &Peking Union Medical College","place":["Beijing, China"]},{"name":"Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/jpm11010037","article-title":"Pharmacogenetics of direct oral anticoagulants: a systematic review","volume":"11","author":"Raymond","year":"2021","journal-title":"J Pers Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17539447241249886","DOI":"10.1177\/17539447241249886","article-title":"Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants","volume":"18","author":"Abdrakhmanov","year":"2024","journal-title":"Ther Adv Cardiovasc Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1002\/cpt.2714","article-title":"Personalizing direct oral anticoagulant therapy for a diverse population: role of race, kidney function, drug 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