{"id":138447,"date":"2024-09-01T12:37:58","date_gmt":"2024-09-01T16:37:58","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=138447"},"modified":"2024-09-01T12:37:58","modified_gmt":"2024-09-01T16:37:58","slug":"oceanic-af-asundexian-is-inferior-to-apixaban-for-stroke-prevention-in-patients-with-atrial-fibrillation","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=138447","title":{"rendered":"OCEANIC AF \u2013 Asundexian is inferior to apixaban for stroke prevention in patients with atrial fibrillation"},"content":{"rendered":"<p><span style=\"font-weight: 400;\">Key Points:<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">Factor XIa inhibition may reduce stroke risk while causing bleeding.<\/span><\/li>\n<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">In this phase III trial, asundexian, a factor XIa inhibitor, was associated with a higher incidence of stroke or systemic embolism than apixaban but had fewer bleeding events.<\/span><\/li>\n<\/ul>\n<p><!--more--><\/p>\n<p><span style=\"font-weight: 400;\">Among patients with atrial fibrillation (AF) and an annual stroke risk of at least 2.2%, the guideline-recommended first-line treatment is a direct oral anticoagulant (DOAC) for stroke prevention. However, patients on DOACs have an annual bleeding risk between 2.7% and 3.5%, which may contribute to the underuse of anticoagulation in patients with AF. In the phase II PACIFIC-AF trial, asundexian, a new oral factor XIa inhibitor, showed a significant reduction in bleeding compared to apixaban.<\/span><span style=\"font-weight: 400;\">1<\/span><span style=\"font-weight: 400;\"> Building on these findings, the OCEANIC AF trial, a large phase III study, tested whether asundexian could prevent stroke and systemic embolism to the same extent as apixaban.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">The trial sponsor, Bayer, announced the early termination of the trial in November 2023 based on the recommendation of the study\u2019s Independent Data Monitoring Committee (IDMC) after ongoing surveillance showed inferior efficacy of asundexian compared to the control arm. On September 1, 2024, Dr. Manesh Patel from Duke University Medical Center, USA, presented the results of the OCEANIC-AF trial in a Hot Lines session with simultaneous publication in <\/span><a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2407105\"><span style=\"font-weight: 400;\">NEJM<\/span><\/a><span style=\"font-weight: 400;\">.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">In this double-blind, randomized trial, patients with AF who met guideline recommendations for anticoagulation (CHA2DS2-VASc score \u22652 for men or \u22653 for women) were randomized 1:1 to receive asundexian 50 mg once daily or standard dosing with apixaban (5 mg or 2.5 mg twice daily based on dose-reduction criteria). The primary efficacy and safety endpoints were the prevention of stroke or systemic embolism and the reduction of major bleeding, respectively.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">At the time of trial termination, 14,830 patients (out of a planned 18,000) had been randomized (mean age 73.9 years, 35% women). The average CHA2DS2-VASc score was 4.3, and 17% had previously taken an oral anticoagulant for 6 weeks or less. <\/span><span style=\"font-weight: 400;\">Compared to apixaban, patients on asundexian had a significantly higher risk of stroke or systemic embolism (1.3% vs. 0.4%; HR 3.79 [95% CI 2.46\u20135.83]). Cardiovascular and all-cause death rates were similar in both arms. <\/span><span style=\"font-weight: 400;\">In the safety population (at the end of treatment plus 2 days), ISTH major bleeding (the primary safety end point) occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55).<\/span><\/p>\n<p><span style=\"font-weight: 400;\">Primary investigator Dr. Patel commented, \u201cOur results show that the dose of asundexian tested was inferior for preventing stroke or systemic embolism compared with apixaban. We could speculate that near-total factor XIa suppression may be needed to prevent thrombus formation. We also noted a lower-than-expected rate of stroke or systemic embolism in the apixaban group, which may reflect prior use of oral anticoagulants and improved medical therapy. Finally, we demonstrated lower bleeding rates with asundexian, which has to be put into context with the stroke findings. There remains a need for better antithrombotic therapy for AF with a lower bleeding risk than current DOACs.\u201d<\/span><\/p>\n<p><span style=\"font-weight: 400;\">References:<\/span><\/p>\n<ol>\n<li><span style=\"font-weight: 400;\">Piccini JP, Caso V, Connolly SJ, et al. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. <\/span><i><span style=\"font-weight: 400;\">Lancet<\/span><\/i><span style=\"font-weight: 400;\">. 2022;399(10333):1383-1390. doi:10.1016\/S0140-6736(22)00456-1<\/span><\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Key Points: Factor XIa inhibition may reduce stroke risk while causing bleeding. In this phase III trial, asundexian, a factor XIa inhibitor, was associated with a higher incidence of stroke or systemic embolism than apixaban but had fewer bleeding events.<\/p>\n","protected":false},"author":40603,"featured_media":114972,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[892,8],"tags":[45,893,47,185],"ppma_author":[1029],"class_list":{"0":"post-138447","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-esc-2024","8":"category-news","9":"tag-conference","10":"tag-esc-2024","11":"tag-featured","12":"tag-news","13":"author-leah-kosyakovsky"},"authors":[{"term_id":1029,"user_id":40603,"is_guest":0,"slug":"leah-kosyakovsky","display_name":"Leah Kosyakovsky","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/864bde69f6f1f80e91e4a97f0a0ba8daa64c2bb702be09ed787444c7dfa045bb?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138447","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40603"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=138447"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138447\/revisions"}],"predecessor-version":[{"id":138448,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/138447\/revisions\/138448"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/114972"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=138447"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=138447"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=138447"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=138447"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}