{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:51:22Z","timestamp":1753887082971,"version":"3.41.2"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">People with kidney failure have a high risk of cardiovascular morbidity\/death, including thromboembolic events. Factor XIa inhibitors are a new class of anticoagulants in development that may offer antithrombotic benefits with a lower risk of incremental bleeding events than traditional therapies. We investigated major adverse vascular events (MAVEs), a relevant composite outcome for testing novel antithrombotic agents, in a large cohort of patients on hemodialysis, to better understand the key requirements to adequately design a phase 3 trial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We included 25\u2009211 patients on hemodialysis for &gt;90\u2009days in phases 4 to 7 (2009\u20132021) of the DOPPS (Dialysis Outcomes and Practice Patterns Study). Atherosclerotic cardiovascular disease (ASCVD) was defined as history\/presence of coronary, peripheral, or cerebrovascular disease. We estimated MAVE rates and cumulative incidence, overall and by ASCVD. Over half (52%) of the cohort met the ASCVD criteria. The MAVE hospitalization\/death composite rate (per 100 patient\u2010years) was 6.0 in the overall cohort and 8.7 in the ASCVD subset. Three\u2010year cumulative incidence of MAVE was 13% in the overall cohort and 18% in the ASCVD subset. The estimated sample size to be randomized in a hypothetical trial in the ASCVD population was \u22487000 patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Even in the enriched ASCVD group, the observed MAVE incidence combined with a high competing risk, regulatory requirements (\u03b1=0.01), and limited recruitment pool makes feasibility of a potential randomized trial targeting MAVE reduction challenging. These results highlight key considerations and challenges for developers of novel therapies targeting systemic thromboembolic events in patients on hemodialysis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.033983","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T03:53:03Z","timestamp":1735098783000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Thromboembolic Events in the Hemodialysis Setting: Understanding Risk Profiles and Cumulative Incidences to Inform Clinical Trial Design"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-5360","authenticated-orcid":false,"given":"Angelo","family":"Karaboyas","sequence":"first","affiliation":[{"name":"Arbor Research Collaborative for Health Ann Arbor MI 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