{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:14:13Z","timestamp":1788369253381,"version":"build-2803163510"},"reference-count":31,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To compare pharmacokinetic, clinical outcomes, and regulatory evidence for apixaban 5 mg versus 2.5 mg twice daily in kidney failure on hemodialysis with atrial fibrillation (AF), and propose a framework for individualized dose selection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources:<\/jats:title>\n                    <jats:p>PubMed, EMBASE, and the Cochrane Library were searched from inception through June 2026 using terms including apixaban, kidney failure, hemodialysis, AF, pharmacokinetics (PK), and dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Selection and Data Extraction:<\/jats:title>\n                    <jats:p>PK studies, observational cohorts, randomized controlled trials (RCTs), network meta-analyses, regulatory documents, and guidelines evaluating apixaban dosing in kidney failure and AF were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Synthesis:<\/jats:title>\n                    <jats:p>Five PK studies (n\u2009\u2248\u2009112) showed 2.5 mg twice daily produced steady-state levels comparable to 5 mg in normal renal function, while 5 mg produced approximately 3-fold supratherapeutic exposure. Of the 3 observational studies, 2 linked 5 mg to lower mortality; 1 found 63% higher bleeding with 5 mg and no difference in stroke\/systemic embolism (subdistribution hazard ratio (SHR) 1.01; 95% CI, 0.59-1.73) or death (hazard ratio [HR] 1.03; 95% CI, 0.77-1.38). Two RCTs (RENAL-AF and AXADIA-AFNET 8) were terminated early and remain underpowered. Confounding by indication, competing risk of death, and misapplication of dose-reduction criteria likely explain this paradox.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance to Patient Care and Clinical Practice:<\/jats:title>\n                    <jats:p>This review provides the first systematic reconciliation of this paradox, identifying confounding by indication, competing risk of death, and structural flaws in the US Food and Drug Administration (FDA) dose-reduction criteria as likely explanations for the discordance. It gives clinical pharmacists a framework for appraising the evidence rather than defaulting to the FDA label or PK data alone, and proposes a decision algorithm for individualized dosing, derived from expert opinion, PK, and observational data and requiring prospective validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The optimal apixaban dose in kidney failure remains unresolved. Neither dose has been shown to reduce stroke versus no anticoagulation in this population. Dose selection should be individualized to patient-specific factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10600280261479334","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:07:03Z","timestamp":1788152823000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Apixaban Dose Selection in Kidney Failure: Reconciling Pharmacokinetics and Clinical Outcomes"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7906-0696","authenticated-orcid":false,"given":"Soon H.","family":"Yang","sequence":"first","affiliation":[{"name":"Pharmacy Practice, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_3_2_2_2","unstructured":"U.S. Food and Drug Administration. 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