{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:15:01Z","timestamp":1778742901362,"version":"3.51.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Res Cardiol"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure\u00a0(HF) might explain any potential effect on clinical outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of\u2009\u2265\u20090.3\u00a0mg\/dL and\u2009\u2265\u200925%, or increase in estimated glomerular filtration rate of\u2009\u2265\u200925% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF\/renal failure.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64\u20132.15, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60\u20130.83, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99\u20131.04), ACM HR 1.01 (0.99\u20131.03), HF\/renal failure hospitalization HR 0.99 (0.97\u20131.00)].<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                <jats:p>Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.<\/jats:p>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00392-022-02144-6","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T11:14:46Z","timestamp":1674126886000},"page":"901-910","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure"],"prefix":"10.1007","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3679-168X","authenticated-orcid":false,"given":"I. E.","family":"Beldhuis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. M.","family":"ter Maaten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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Greenberg received honoraria from Novartis for participation in the Executive Committee for studies of serelaxin in acute heart failure. B. Davison is an employee of Momentum Research, Inc., which has received grants from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics Inc., Corteria Pharmaceuticals, Roche Diagnostics Inc., Sanofi, Windtree Therapeutics Inc. and XyloCor Therapeutics. G. Cotter is an employee of Momentum Research, Inc. which has received grants from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics Inc., Corteria Pharmaceuticals, Roche Diagnostics Inc., Sanofi, Windtree Therapeutics Inc. and XyloCor Therapeutics. M Felker has received research grants from NHLBI, American Heart Association, Amgen, Bayer, BMS, Merck, Cytokinetics, and CSL-Behring; he has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Medtronic, Cardionomic, Boehringer-Ingelheim, American Regent, Abbott, Astra-Zeneca, Reprieve, Myovant, Sequana, Windtree Therapuetics, and Whiteswell, and has served on clinical endpoint committees\/data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, LivaNova, Siemens, and Rocket Pharma. G. Gimpelewicz and T. Severin are Novartis employees. G. Filippatos is a committee member and\/or has received lecture fees from Bayer, Boehringer Ingelheim, Vifor, Servier, Novartis, Medtronic, and Amgen. All other authors have no disclosures to report. The RELAX-AHF2 trial was sponsored by Novartis Pharma.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}