{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T07:16:02Z","timestamp":1788074162152,"version":"build-2784847793"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"abstract":"\n BACKGROUND:<\/jats:title>\n Stimulation of the relaxin family peptide receptor 1 experimentally reduces systemic vascular resistance and afterload, improves organ perfusion, and fosters reverse cardiac remodeling. We hypothesized that AZD5462, an oral once-daily relaxin family peptide receptor 1 agonist, may benefit individuals with chronic heart failure (HF).<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n In this international, multicenter, double-blind, placebo-controlled, dose-ranging trial, adults with chronic HF and left ventricular ejection fraction \u226435% (cohort A) or 41% to 55% (cohort B) were randomized 1:1:1:1 to 3 (20, 80, or 360 mg) once-daily oral doses of AZD5462 or placebo. Primary end points were changes in end-systolic volume index (cohort A) and systemic vascular resistance index (cohort B) after 24 weeks.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n A total of 235 (cohort A) and 140 (cohort B) participants were randomized across 57 sites in 10 countries. The mean age was 65 and 70 years, and 88% and 69% were male; baseline concomitant guideline-directed medical therapy for HF was excellent. Treatment with AZD5462 was well tolerated compared with placebo. In cohort A, at week 25, treatment with AZD5462 20 mg showed a placebo-adjusted end-systolic volume index change from baseline of \u22125.4 mL\/m\n 2<\/jats:sup>\n (95% CI, \u221210.9 to 0.1;\n P<\/jats:italic>\n =0.054). In cohort B, AZD5462 treatment resulted in significant placebo-adjusted reductions in systemic vascular resistance index at week 25 across all dose groups (all\n P<\/jats:italic>\n <0.05).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n Among individuals with well-treated chronic HF, the addition of oral AZD5462 was well tolerated and demonstrated encouraging effects on cardiovascular hemodynamic measures across a wide range of left ventricular ejection fraction. Larger and longer duration trials are warranted to assess the impact of AZD5462 on clinical outcomes in HF.<\/jats:p>\n <\/jats:sec>\n \n REGISTRATION:<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT06299826.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.126.082763","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T07:09:56Z","timestamp":1788073796000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Relaxin Receptor Agonist AZD5462 in Participants With Chronic Heart Failure: Primary Results From the LUMINARA Trial"],"prefix":"10.1161","clinical-trial-number":[{"clinical-trial-number":"nct06299826","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-1798","authenticated-orcid":true,"suffix":"Jr","given":"James L.","family":"Januzzi","sequence":"first","affiliation":[{"name":"Baim Institute for Clinical Research, Massachusetts General Hospital, Harvard Medical School, Boston (J.L.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2401-0235","authenticated-orcid":true,"given":"Jaya B.","family":"Rosenmeier","sequence":"additional","affiliation":[{"name":"Early Clinical Development, Cardiovascular, Renal and Metabolism (J.B.R., M.P.Q.-H.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ely Pizzato","sequence":"additional","affiliation":[{"name":"Early Clinical Development, Cardiovascular, Renal and Metabolism (P.E.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6341-4286","authenticated-orcid":true,"given":"Macarena P.","family":"Quintana-Hayashi","sequence":"additional","affiliation":[{"name":"Early Clinical Development, Cardiovascular, Renal and Metabolism (J.B.R., M.P.Q.-H.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6005-0710","authenticated-orcid":true,"given":"Lai-Shan Melanie","family":"Chan","sequence":"additional","affiliation":[{"name":"iometrics, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mississauga, ON, Canada (L.-S.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Johannesson","sequence":"additional","affiliation":[{"name":"Global Patient Safety (P.J.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrali S.","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"CSB: Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences (C.S.B.) 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