{"doi":"10.1161/strokeaha.120.030565","title":"Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy","abstract":"Background and Purpose: Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors) with intracranial hemorrhage (ICrH). Methods: ANNEXA-4 was a single-arm study evaluating andexanet in patients presenting with major bleeding ≤18 hours after taking an FXa inhibitor. Patients received a bolus plus 2-hour infusion of andexanet. Brain imaging in patients with ICrH was performed at baseline and at 1 and 12 hours postandexanet infusion. Coprimary efficacy outcomes were change in anti-FXa activity and hemostatic efficacy at 12 hours (excellent/good efficacy defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included occurrence of thrombotic events and death at 30 days. Results: A total of 227 patients with ICrH were included in the safety population (51.5% male; mean age 79.3 years) and 171 in the efficacy population (99 spontaneous and 72 traumatic bleeds). In efficacy evaluable patients, excellent/good hemostasis 12 hours postandexanet occurred in 77 out of 98 (78.6%) and in 58 out of 70 (82.9%) patients with spontaneous and traumatic bleeding, respectively. In the subanalysis by FXa inhibitor treatment group in the efficacy population, median of percent change in anti-FXa from baseline to nadir showed a decrease of 93.8% for apixaban-treated patients (n=99) and by 92.6% for rivaroxaban-treated patients (n=59). Within 30 days, death occurred in 34 out of 227 (15.0%) patients and thrombotic events occurred in 21 out of 227 (9.3%) patients (safety population). Conclusions: Andexanet reduced anti-FXa activity in FXa inhibitor-treated patients with ICrH, with a high rate of hemostatic efficacy. Andexanet may substantially benefit patients with ICrH, the most serious complication of anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02329327.","journal":"Stroke","year":2021,"id":154068,"datarank":2.2271976234663757,"base_score":4.189654742026425,"endowment":4.189654742026425,"self_citation_contribution":0.6284482113039639,"citation_network_contribution":1.5987494121624117,"self_endowment_contribution":0.6284482113039639,"citer_contribution":1.5987494121624117,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":55,"citers_with_citation_signal":42,"citers_with_endowment":42,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8951,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02329327"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653244,"name":"Patrick Yue","orcid":"0009-0000-2884-9151","position":1,"is_corresponding":false},{"id":653245,"name":"Elena Zotova","orcid":"0000-0003-0645-1243","position":2,"is_corresponding":false},{"id":654230,"name":"Juliet Nakamya","orcid":null,"position":3,"is_corresponding":false},{"id":274255,"name":"Lizhen Xu","orcid":"0000-0003-4921-7238","position":4,"is_corresponding":false},{"id":653246,"name":"Truman J. Milling","orcid":"0000-0002-5588-0426","position":5,"is_corresponding":false},{"id":653247,"name":"Tomoyuki Ohara","orcid":"0000-0002-8116-4730","position":6,"is_corresponding":false},{"id":256551,"name":"Joshua N. Goldstein","orcid":"0000-0002-6406-1828","position":7,"is_corresponding":false},{"id":617972,"name":"Saskia Middeldorp","orcid":"0000-0002-1006-6420","position":8,"is_corresponding":false},{"id":334038,"name":"Peter Verhamme","orcid":"0000-0001-8698-2858","position":9,"is_corresponding":false},{"id":55179,"name":"José López‐Sendón","orcid":"0000-0002-0871-9197","position":10,"is_corresponding":false},{"id":342594,"name":"Pamela B. Conley","orcid":"0000-0001-9400-6531","position":11,"is_corresponding":false},{"id":654231,"name":"John T. Curnutte","orcid":null,"position":12,"is_corresponding":false},{"id":56149,"name":"John W. Eikelboom","orcid":"0000-0003-4126-1285","position":13,"is_corresponding":false},{"id":653248,"name":"Mark Crowther","orcid":"0000-0003-4986-4873","position":14,"is_corresponding":false},{"id":56134,"name":"Stuart J. Connolly","orcid":"0000-0002-7377-335X","position":15,"is_corresponding":false},{"id":654232,"name":"on behalf of the ANNEXA-4 Investigators","orcid":null,"position":16,"is_corresponding":false},{"id":653243,"name":"Andrew M. Demchuk","orcid":"0000-0002-4930-7789","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T23:43:49.684414Z","pmid":"33966491","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":[]}