{"doi":"10.1016/j.rpth.2023.102167","title":"Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial","abstract":"Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.","journal":"Research and Practice in Thrombosis and Haemostasis","year":2023,"id":369632,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":451916,"name":"Erinn M. Hade","orcid":"0000-0001-8977-6443","position":1,"is_corresponding":false},{"id":409500,"name":"Lucy Z. Kornblith","orcid":"0000-0002-1861-9691","position":2,"is_corresponding":false},{"id":617964,"name":"Lana A. Castellucci","orcid":"0000-0003-1322-9368","position":3,"is_corresponding":false},{"id":51219,"name":"Mary Cushman","orcid":"0000-0002-7871-6143","position":4,"is_corresponding":false},{"id":227543,"name":"Michael E. Farkouh","orcid":"0000-0002-8095-0246","position":5,"is_corresponding":false},{"id":105988,"name":"Michelle N. Gong","orcid":"0000-0001-7952-5384","position":6,"is_corresponding":false},{"id":308324,"name":"Anna Heath","orcid":"0000-0002-7263-4251","position":7,"is_corresponding":false},{"id":1128978,"name":"B. J. Hunt","orcid":null,"position":8,"is_corresponding":false},{"id":802939,"name":"Keri S. Kim","orcid":"0000-0002-8480-4801","position":9,"is_corresponding":false},{"id":694696,"name":"Andrei Kindzelski","orcid":null,"position":10,"is_corresponding":false},{"id":430390,"name":"Patrick R. Lawler","orcid":"0000-0001-5155-5071","position":11,"is_corresponding":false},{"id":140241,"name":"David E. Leaf","orcid":"0000-0001-7875-090X","position":12,"is_corresponding":false},{"id":272521,"name":"Ewan C. Goligher","orcid":"0000-0002-0990-6701","position":13,"is_corresponding":false},{"id":244904,"name":"Eric Leifer","orcid":"0000-0001-6888-8307","position":14,"is_corresponding":false},{"id":3878,"name":"Bryan J. McVerry","orcid":"0000-0002-1175-4874","position":15,"is_corresponding":false},{"id":225668,"name":"Harmony R. Reynolds","orcid":"0000-0003-0284-0655","position":16,"is_corresponding":false},{"id":267667,"name":"Ryan Zarychanski","orcid":"0000-0001-9455-6138","position":17,"is_corresponding":false},{"id":225667,"name":"Judith S. Hochman","orcid":"0000-0002-5889-5981","position":18,"is_corresponding":false},{"id":280758,"name":"Matthew D. Neal","orcid":"0000-0001-8931-6236","position":19,"is_corresponding":false},{"id":225663,"name":"Jeffrey S. Berger","orcid":"0000-0001-8216-4647","position":20,"is_corresponding":false},{"id":228052,"name":"Nathaniel R. Smilowitz","orcid":"0000-0002-6823-2815","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T01:15:32.670954Z","pmid":"37727846","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":[]}