{"doi":"10.1002/cpt.2131","title":"Thromboembolic and Hemorrhagic Outcomes in the Direct Oral Anticoagulant Trials Across the Spectrum of Kidney Function","abstract":"Chronic kidney disease is a common comorbidity among patients taking direct‐acting oral anticoagulants (DOACs). Herein, we evaluate the influence of kidney function on stroke or systemic embolism (SEE), hemorrhage, and composite end points (stroke/SEE/hemorrhage/death and stroke/SEE/death) among patients on DOACs and warfarin. Baseline kidney function was categorized as glomerular filtration rate (GFR) ≥ 60 (reference), 45–59, and < 45mL/min/1.73 m 2 for participants in the Randomized Evaluation of Long‐Term Anticoagulant Therapy (RE‐LY) ( n = 18,049), Apixaban for Reduction in Stroke and Other Thromboembolic Events (ARISTOTLE) ( n = 18,187), and The Effective Anticoagulation with Factor Xa Next Generation in AF (ENGAGE AF) ( n = 20,798) trials. Incidence of events was compared across GFR categories. Hazard ratios for events were estimated using Cox regression using intention‐to‐treat analysis adjusting for known predictors. A large proportion of participants had GFR < 60 (25–29% had 45 ≤ GFR < 60 and 9.5–12.6% with GFR < 45). Compared with patients with GFR ≥ 60, warfarin users across the trials with GFR ≥ 45–59 and GFR < 45 had a higher incidence of hemorrhage ( P values < 0.0001) and warfarin users in the ARISTOTLE and ENGAGE trials had higher incidence of stroke/SEE ( P values ≤ 0.05). Compared with patients with GFR ≥ 60, dabigatran users with GFR ≥ 45–59 and GFR < 45 had a higher incidence of stroke/SEE ( P ≤ 0.02), hemorrhage ( P < 0.001), and both composite end points ( P < 0.0001). Compared with patients with GFR ≥ 60, apixaban and edoxaban users with GFR ≥ 45–59 and GFR < 45 had a higher incidence of hemorrhage ( P values ≤ 0.05) and composite end points ( P values ≤ 0.05). After adjustment, compared with patients with GFR ≥ 60, warfarin users with GFR < 60 in the ARISTOTLE and RE‐LY trials had a higher risk of hemorrhage ( P < 0.05), as did dabigatran ( P < 0.001) and edoxaban ( P ≤ 0.005) users, while apixaban users did not exhibit an increased risk ( P = 0.08 GFR ≥ 45–59; P = 0.71 GFR < 45). Kidney function significantly influences the safety and efficacy of oral anticoagulants.","journal":"Clinical Pharmacology & Therapeutics","year":2020,"id":73408,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":350045,"name":"T. Mark Beasley","orcid":"0000-0002-0803-1915","position":1,"is_corresponding":false},{"id":386044,"name":"Jielin Sun","orcid":"0009-0006-9178-055X","position":2,"is_corresponding":false},{"id":290058,"name":"Norman Stockbridge","orcid":null,"position":3,"is_corresponding":false},{"id":386796,"name":"Michael Pacanowski","orcid":null,"position":4,"is_corresponding":false},{"id":386045,"name":"Jeffry Florian","orcid":"0009-0000-1984-8026","position":5,"is_corresponding":false},{"id":386043,"name":"Nita A. Limdi","orcid":"0000-0002-4672-8406","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T21:45:32.034078Z","pmid":"33278832","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}